Generating the evidence to support the establishment of a Respiratory Syncytial Virus surveillance system in Cameroon: A study protocol.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the major pathogens frequently associated with severe respiratory tract infections in younger children and older adults globally. There is an unmet need with a lack of routine country-specific databases and/or RSV surveillance systems on RSV disease burden among adults in most low- and middle-income countries, including Cameroon. We aim to estimate the adult RSV burden needed to develop a framework for establishing an RSV surveillance database in Cameroon. METHODS AND ANALYSIS: A two-phase study approach will be implemented, including a literature review and a review of medical records. First, a systematic review of available literature will provide insights into the current burden of RSV in adults in Cameroon, searching the following databases: Global Health, PubMed, CINAHL, Embase, African Journal Online Library, Scopus, Global Index Medicus, Cochrane databases, and grey literature search. Identified studies will be included if they reported on the RSV burden of disease among Cameroonian adults aged ≥18 years from 1st January 1990 to 31st December 2023. A narrative synthesis of the evidence will be provided. A meta-analysis will be conducted using a random effect model, when feasible. Two co-authors will independently perform data screening, extraction, and synthesis and will be reported according to the PRISMA-P guidelines for writing systematic review protocols. Secondly, a retrospective cohort design will permit data analysis on RSV among adults in the laboratory registers at the National Influenza Center. Medical records will be reviewed to link patients' files from emanating hospitals to capture relevant demographic, laboratory, and clinical data. The International Classification of Diseases and Clinical Modifications 10th revision (ICD-10-CM) codes will be used to classify the different RSV outcomes retrospectively. RESULTS: The primary outcome is quantifying the RSV burden among the adult population, which can help inform policy on establishing an RSV surveillance database in Cameroon. The secondary outcomes include (i) estimates of RSV prevalence among Cameroonian adult age groups, (ii) RSV determinants, and (iii) clinical outcomes, including proportions of RSV-associated morbidity and/or death among age-stratified Cameroonian adults with medically attended acute respiratory tract infections. CONCLUSIONS: The evidence generated from the two projects will be used for further engagement with relevant stakeholders, including policymakers, clinicians, and researchers, to develop a framework for systematically establishing an RSV surveillance database in Cameroon. This study proposal has been registered (CRD42023460616) with the University of York Center for Reviews and Dissemination of the International Prospective Register of Systematic Reviews (PROSPERO).

Agreement between self-reported and registered age at asthma diagnosis in Finland.

INTRODUCTION: In epidemiological studies, the age at asthma onset is often defined by patients' self-reported age at diagnosis. The reliability of this report might be questioned. Our objective was to evaluate the agreement between self-reported and registered age at asthma diagnosis and assess features contributing to the agreement. METHODS: As part of the FinEsS respiratory survey in 2016, randomly selected population samples of 13,435 from Helsinki and 8000 from Western Finland were studied. Self-reported age at asthma diagnosis was compared to age at asthma diagnosis registered in the Finnish register on special reimbursement for asthma medication. The reimbursement right is based on lung function criteria according to GINA and Finnish guidelines. If the difference was less than 5 years, self-reported diagnosis was considered reliable. Features associated with the difference between self-reported and registered age at asthma diagnosis were evaluated. RESULTS: Altogether 197 subjects from Helsinki and 144 from Western Finland were included. Of these, 61.9% and 77.8%, respectively, reported age at diagnosis reliably. Median difference between self-reported and registered age at diagnoses was - 2.0 years (IQR - 9.0 to 0) in Helsinki and - 1.0 (IQR - 4.3 to 0) in Western Finland indicating earlier self-reported age at diagnosis. More reliable self-report was associated with non-allergic subjects and subjects who reported having asthma diagnosis more recently. CONCLUSIONS: Agreement between self-reported and registered age at asthma diagnosis was good especially with adult-onset asthma patients. Poor agreement in early-onset asthma could be related to delay in registration due to reimbursement criteria.

Level of Education Modifies Asthma Mortality in Norway and Sweden. The Nordic EpiLung Study.

Background and Aim: The relationship between socioeconomic status (SES), asthma and mortality is complex and multifaceted, and it is not established if educational level modifies the association between asthma and mortality. The aim was to study the association between asthma and mortality in Sweden and Norway and to what extent educational level modifies this association. Participants and Methods: Within the Nordic EpiLung Study, >56,000 individuals aged 30-69 years participated in population-based surveys on asthma and associated risk factors in Sweden and Norway during 2005-2007. Data on educational level and 10-year all-cause mortality were linked by national authorities. The fraction of mortality risk attributable to asthma was calculated, and Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for mortality related to asthma, stratified by educational level. Results: In total, 5.5% of all deaths was attributed to asthma. When adjusted for potential confounders, the HR for mortality related to asthma was 1.71 (95% CI 1.52-1.93). Those with primary level of education had higher hazard of all-cause death related to asthma than those with tertiary level (HR 1.80, 95% CI 1.48-2.18, vs HR 1.39, 95% CI 0.99-1.95). Conclusion: Asthma was associated with an overall 71% increased all-cause mortality and 5.5% of deaths can be attributed to asthma. Educational levels modified the risk of mortality associated with asthma, with the highest risk among those with primary education.

All-cause and cause-specific mortality by spirometric pattern and sex - a population-based cohort study.

BACKGROUND: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. OBJECTIVES: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). DESIGN: Population-based prospective cohort study. METHODS: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC ⩾ 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC ⩾ 0.70 and FVC ⩾ 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. RESULTS: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. CONCLUSION: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.

All-cause and cause specific mortality in relation to different lung function patterns and sex; normal, obstructive and restricted lung functionChronic airway obstruction and restrictive spirometry pattern are associated with mortality, but sex specific patterns have hardly been evaluated.Aim: To study possible sex-dependent differences of all-cause and cause-specific mortality among men and women with chronic airway obstruction and restrictive spirometry pattern, respectively, compared to that of normal lung function.Methods: Individuals with chronic airway obstruction, restrictive spirometry pattern and normal lung function were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-04. Mortality data were collected through April 2016, totally covering 19,000 patient-years of observation time. We analyzed the Hazard Ratios for all-cause and cause-specific death comparing chronic airway obstruction and restrictive spirometry pattern to that of normal lung function, adjusting for age, body mass index, sex, smoking habits and pack-years. Similar analyses were conducted separately for men and women.Results: The hazard for all-cause mortality was higher in both chronic airway obstruction and restrictive spirometry pattern than in normal lung function and, the higher hazards were male-driven. In chronic airway obstruction the hazard of respiratory and cardiovascular deaths higher than in those with normal lung function. The increased hazard of respiratory death was significant in women while the increased hazard of cardiovascular death was significant in men. In restrictive spirometry pattern, the higher hazard for respiratory but not cardiovascular death persisted after adjustment, similarly in both sexes.Conclusions: The higher hazard for all-cause mortality in chronic airway obstruction and restrictive spirometry pattern than in normal lung function was male-driven. Chronic airway obstruction associated with respiratory death in women and cardiovascular death in men, while restrictive pattern associated with respiratory death, similarly in both sexes.

Is there still a social gradient in respiratory symptoms? A population-based Nordic EpiLung-study.

BACKGROUND: Respiratory symptoms are a common public health issue that can partly be attributed to preventable risk factors, such as tobacco smoking and occupational exposure, which are more common in individuals with lower socioeconomic status. OBJECTIVE: Our aim was to evaluate the social gradient in respiratory symptoms in Nordic countries. METHODS: This study included participants aged 30-65 years from five cross-sectional population-based questionnaire surveys in 2016 in Finland and Sweden (N = 25,423) and in 2017-2019 in Norway (N = 27,107). Occupational skill levels 1 and 2 (occupations requiring compulsory education) were combined and compared to skill levels 3 and 4 (occupations requiring upper secondary and tertiary education). Meta-analysis was conducted to obtain pooled age- and sex adjusted odds ratios (aORs) of associations between occupational skill and the respiratory symptoms including recurrent wheeze, dyspnoea, and productive cough. RESULTS: In the meta-analysis, recurrent wheeze, dyspnoea, and productive cough showed a social gradient. The participants with occupational skill 1 and 2 had higher risk for recurrent wheeze (aOR 1.78, 95% CI 1.34-2.22) and dyspnoea (aOR 1.59, 95% CI 1.29-1.90) compared to occupational skill 3 and 4 in Sweden and Finland. Similarly increased risk was observed for combined assessment of dyspnoea and wheeze (aOR 1.05, 95% CI 1.03-1.07) in Norway. In a meta-analysis including all three countries, the aOR for productive cough was 1.31 95% CI 1.07-1.56. CONCLUSIONS: Occupations with lower, compared to higher, skill levels were associated with an increased risk of recurrent wheeze, dyspnoea, and productive cough.

Mortality in patients with adrenal insufficiency: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Adrenal insufficiency (AI) is a rare disorder characterised by an impaired secretion of glucocorticoids from the adrenal glands. Treatment strategies for AI have developed over time with reduced glucocorticoid replacement doses and improved circadian exposure regimens, but whether this has resulted in better survival is unknown. The main purpose of this systematic review is to gather and synthesise available evidence on long-term mortality in patients with AI. The secondary aim is to study causes of death, with focus on cardiovascular and infectious diseases, in AI patients. METHODS AND ANALYSIS: Studies published from the inception of respective databases (Medline, Embase, Cochrane and Web of Science) until the end of May 2023 will be systematically synthetised. Observational studies with a reference population will be included, and their quality will be assessed using the Newcastle-Ottawa scale. Data collected will be narratively integrated and a meta-analysis will be performed to pool data from studies considered homogeneous. The systematic review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This will be the first systematic review assessing mortality and causes of death in AI patients. The findings of this systematic review will be of value for both patients and healthcare providers. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval or informed consent because it will be based on previously published data only and does not implicate any direct contact with individual patients. The research results will be presented at scientific conferences and submitted for publication in an internationally recognised peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42023416253.

Prevalence of tree nut allergy in Europe: A systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions.

Exogenous female sex steroid hormones and new-onset asthma in women: a matched case-control study.

BACKGROUND: Evidence on the role of exogenous female sex steroid hormones in asthma development in women remains conflicting. We sought to quantify the potential causal role of hormonal contraceptives and menopausal hormone therapy (MHT) in the development of asthma in women. METHODS: We conducted a matched case-control study based on the West Sweden Asthma Study, nested in a representative cohort of 15,003 women aged 16-75 years, with 8-year follow-up (2008-2016). Data were analyzed using Frequentist and Bayesian conditional logistic regression models. RESULTS: We included 114 cases and 717 controls. In Frequentist analysis, the odds ratio (OR) for new-onset asthma with ever use of hormonal contraceptives was 2.13 (95% confidence interval [CI] 1.03-4.38). Subgroup analyses showed that the OR increased consistently with older baseline age. The OR for new-onset asthma with ever MHT use among menopausal women was 1.17 (95% CI 0.49-2.82). In Bayesian analysis, the ORs for ever use of hormonal contraceptives and MHT were, respectively, 1.11 (95% posterior interval [PI] 0.79-1.55) and 1.18 (95% PI 0.92-1.52). The respective probability of each OR being larger than 1 was 72.3% and 90.6%. CONCLUSIONS: Although use of hormonal contraceptives was associated with an increased risk of asthma, this may be explained by selection of women by baseline asthma status, given the upward trend in the effect estimate with older age. This indicates that use of hormonal contraceptives may in fact decrease asthma risk in women. Use of MHT may increase asthma risk in menopausal women.

Sensitization patterns to cat molecular allergens in subjects with allergic sensitization to cat dander.

BACKGROUND: The use of molecular allergology has increasingly become common in the diagnosis and management of allergic diseases. However, there is still a lack of data on cat molecular allergens in adults. Therefore, we aimed to uncover the sensitization patterns to cat molecular allergens. METHODS: Participants were recruited from the West Asthma Sweden Study, a population-based study enriched with asthma subjects aged 16-75 years. Of 1872, 361 individuals were positive for cat dander immunoglobulin E and were further analysed for cat molecular allergens (Fel d 1/2/4/7). Sensitization patterns were classified as monosensitization, polysensitization, and concomitant sensitization, and were related to demographic and clinical measurements. RESULTS: Among cat-sensitized subjects, 84.2% were sensitized to secretoglobin, while 42.4% were sensitized to lipocalins. Nearly half of the subjects were monosensitized to Fel d 1. Polysensitization was observed in 20.2%, and concomitant sensitization to protein families was seen in 7.2%. Asthma prevalence, cat exposure, and rural living were associated with poly- and concomitant sensitization to protein families. Concomitant sensitization to single allergens was more common in those with asthma than in those without, while concomitant sensitization to both Fel d 1 and Fel d 4 was the most common pattern in individuals with asthma. Sensitization patterns also differed according to cat ownership and the degree of urbanization. CONCLUSION: Sensitization to molecular allergens was observed in 90.9% of cat-sensitized subjects and showed variations across participants' background characteristics and the presence of asthma. Identification of sensitization patterns to cat allergens might provide better characterization of cat-allergic subjects.

Underdiagnosis and misclassification of COPD in Sweden - A Nordic Epilung study.

INTRODUCTION: The prevalence of COPD tends to level off in populations with decreasing prevalence of smoking but the extent of underdiagnosis in such populations needs further investigation. AIM: To investigate underdiagnosis and misclassification of COPD with a focus on socio-economy, lifestyle determinants and healthcare utilization. METHOD: The 1839 participants were selected from two ongoing large-scale epidemiological research programs: The Obstructive Lung Disease in Northern Sweden Studies and the West Sweden Asthma Study. COPDGOLD was defined according to the fixed post-bronchodilator spirometric criteria FEV1/FVC<0.70 in combination with respiratory symptoms. RESULTS: Among the 128 participants who fulfilled the criteria for COPDGOLD, the underdiagnosis was 83.6% (n = 107) of which 57.9% were men. The undiagnosed participants were younger, had higher FEV1% of predicted and less frequently a family history of bronchitis. One in four of the undiagnosed had utilized healthcare and had more frequently utilized healthcare due to a burden of respiratory symptoms than the general population without COPD. Underdiagnosis was not related to educational level. Misclassification of COPD was characterized by being a woman with low education, ever smoker, having respiratory symptoms and having a previous asthma diagnosis. CONCLUSION: In the high income country Sweden, the underdiagnosis of COPD was highly prevalent. Reduced underdiagnosis can contribute to risk factor modification, medical treatment and self-management strategies in early stages of the disease, which may prevent disease progression and improve the quality of life among those affected. Therefore, there is a need to increase the use of spirometry in primary care to improve the diagnostic accuracy.

The Use of DAO as a Marker for Histamine Intolerance: Measurements and Determinants in a Large Random Population-Based Survey.

Histamine intolerance (HIT) is a common adverse reaction to food where elimination and reintroduction of histamine-rich food is part of the investigation. Analysis of the enzyme diamine oxidase (DAO) is sometimes used as an additional tool for diagnosis. This study aimed to describe the distribution of DAO in a large representative cohort of adults and to determine the association between DAO activity and possible associated factors. The study is based on the population-based West Sweden Asthma Study and includes 1051 subjects. Subjects underwent structured interviews including questions on demography, asthma, allergy symptoms, and lifestyle factors. Subjects were assessed for specific-IgE-antibodies and measurement of DAO activity in serum. Previously suggested cut-off levels for low values (<3 U/mL), normal values (>10 U/mL), and median levels of DAO were used. In the group of 1051 subjects, only a few presented reactions upon histamine intake, whereas 44% presented DAO levels below the suggested normal cut-off levels. BMI and age were shown to have an impact on DAO activity among women with increasing activity of DAO with increasing BMI and age. Among men, only increasing age was seen to have an impact on DAO levels. There was no difference in DAO levels with different sensitization status to common foods or airborne allergens. No association between DAO levels and reported symptoms to histamine-rich foods could be found. In conclusion, the determination of the DAO enzyme needs to be re-evaluated and may not be used as a valuable tool for histamine intolerance using current cut-off values. Further studies are needed to improve the use of DAO as a biomarker for histamine intolerance.

Therapeutic outcomes with surgical and medical management for primary aldosteronism: protocol for a systematic review and meta-analysis.

INTRODUCTION: Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether these two different treatment strategies are comparable in mitigating the detrimental effect of PA on outcomes is still debated. OBJECTIVES: The primary aim of this systematic review is to identify, appraise and synthesise existing literature comparing clinical outcomes after treatment in patients with PA. METHODS AND ANALYSIS: A systematic and comprehensive search will be performed using PubMed, Web of Science and EMBASE, for studies published until December 2022. Observational and interventional studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa Scale, while interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesised. We will perform meta-analysis to pool estimates from studies considered to be homogeneous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. ETHICS AND DISSEMINATION: As this study is based solely on the published literature, no ethics approval is required. This review will aim to provide some estimates on outcomes, including survival, rates of clinical and biochemical control, cardiovascular and cerebrovascular events, as well as data on quality of life and renal function, in patients with PA treated surgically or with MR antagonists. The study findings will be presented at scientific meetings and will be published in an international peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42022362506.

Siblings and risk of allergic rhinitis: A systematic review and meta-analysis.

Following the "hygiene hypothesis" and the increase in the prevalence of atopic diseases such as allergic rhinitis, a plethora of studies have investigated the role of sibship composition as a protective factor, but findings are conflicting. The aim of this study was to synthesize the global literature linking birth order and sibship size (number of siblings) to the risk of allergic rhinitis. Fifteen databases were systematically searched, with no restrictions on publication date or language. Observational studies with defined sibship composition (birth order or sibship size) as exposure and allergic rhinitis or allergic rhinoconjunctivitis (self-reported or clinically diagnosed) as outcome were eligible. Study selection, data extraction, and quality assessment were performed independently in pairs. Relevant data were summarized in tables. Comparable numerical data were analyzed using meta-analysis with robust variance estimation (RVE). Seventy-six reports with >2 million subjects were identified. Being second- or later-born child was associated with protection against both current (pooled risk ratio [RR] 0.79, 95% CI 0.73-0.86) and ever (RR 0.77, 95% CI 0.68-0.88) allergic rhinitis. Having siblings, regardless of birth order, was associated with a decreased risk of current allergic rhinitis (RR 0.89, 95% CI 0.83-0.95) and allergic rhinoconjunctivitis (RR 0.92, 95% CI 0.86-0.98). These effects were unchanged across age, time period, and geographical regions. Our findings thus indicate that primarily, a higher birth order, and to a lesser extent the number of siblings, is associated with a lower risk of developing allergic rhinitis.

Prevalence estimates of eight big food allergies in Europe: Updated systematic review and meta-analysis.

In 2014, the European Academy of Allergy and Clinical Immunology published prevalence estimates for food allergy (FA) and food sensitization (FS) to the so-called eight big food allergens (i.e. cow's milk, egg, wheat, soy, peanut, tree nuts, fish and shellfish) in Europe for studies published between 2000 and 2012. The current work provides 10-year updated prevalence estimates for these food allergens. A protocol was registered on PROSPERO before starting the research (reference number CRD42021266657). Six databases were searched for studies published 2012-2021, added to studies published up to 2012, resulting in a total of 93 studies. Most studies were graded as at moderate risk of bias. The overall pooled estimates for all age groups of self-reported lifetime prevalence were as follows: cow's milk (5.7%, 95% confidence interval 4.4-6.9), egg (2.4%, 1.8-3.0), wheat (1.6%, 0.9-2.3), soy (0.5%, 0.3-0.7), peanut (1.5%, 1.0-2.1), tree nuts (0.9%, 0.6-1.2), fish (1.4%, 0.8-2.0) and shellfish (0.4%, 0.3-0.6). The point prevalence of food challenge-verified allergy were as follows: cow's milk (0.3%, 0.1-0.5), egg (0.8%, 0.5-1.2), wheat (0.1%, 0.01-0.2), soy (0.3%, 0.1-0.4), peanut (0.1%, 0.0-0.2), tree nuts (0.04%, 0.02-0.1), fish (0.02%, 0.0-0.1) and shellfish (0.1%, 0.0-0.2). With some exceptions, the prevalence of allergy to common foods did not substantially change during the last decade; variations by European regions were observed.

Intake of vitamin B12 in relation to vitamin B12 status in groups susceptible to deficiency: a systematic review.

Objective: To systematically review the evidence for whether habitual or different levels of experimental intake of vitamin B12 from diet and supplements is sufficient to ensure adequate B12 status in groups most susceptible to vitamin B12 deficiency. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to 21 May 2021, for intervention studies, prospective cohort studies and case-control studies assessing B12 intake from diet and/or supplements in relation to B12 status (s/p-B12, holotranscobalamin, methylmalonic acid, homocysteine or breastmilk B12). Cross-sectional studies were eligible for studies conducted during pregnancy and lactation. Included populations were children (0-18 years), young adults (18-35 years), pregnant or lactating women, older adults (≥65 years) and vegans or vegetarians. Study selection, data extraction and risk of bias assessment were conducted by two assessors independently. The evidence was synthesized qualitatively and classified according to the World Cancer Research Fund. Results: The searches yielded 4855 articles of which 89 were assessed in full text and 18 included. Three studies were conducted during pregnancy and three during lactation or infancy - all observational. Eight studies were conducted among older adults; most were interventions among B12-deficient participants. Four studies were eligible for vegetarian and vegans, all interventions. The strength of evidence that habitual B12 intake or an intake in line with the current Nordic recommended intake (RI) is sufficient to ensure adequate status was considered Limited - no conclusion for all included populations. Conclusion: Evidence is insufficient to assess if or which level of B12 intake is sufficient to maintain adequate status for all included populations. Population-based cohort studies and low-to-moderate dose interventions that address this question are highly warranted.

Legume consumption in adults and risk of cardiovascular disease and type 2 diabetes: a systematic review and meta-analysis.

Objectives: This study aimed to systematically review the evidence for associations between consumption of legumes and cardiovascular disease (CVD), type 2 diabetes (T2D) and their risk factors among healthy adults. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 16 May 2022 for ≥4 weeks long randomized (RCT) and non-randomized controlled trials and prospective cohort studies with follow-up ≥12 months, assessing legume intake (beans/lentils/peas/soybeans, excluding peanuts and legume-products/protein/powder/flour) as the intervention or exposure. Outcomes were CVD, coronary heart disease (CHD), stroke, T2D and in intervention trials only: changes in blood lipids, glycemic markers, and blood pressure. Risk of bias (RoB) was evaluated with Cochrane's RoB2, ROBINS-I, and US Department of Agriculture (USDA)'s RoB-NObS. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk or weighed mean differences with 95% confidence intervals, heterogeneity quantified as I2. The evidence was appraised according to World Cancer Research Fund's criteria. Results: Of the 181 full-text articles assessed for eligibility, 47 were included: 31 cohort studies (2,081,432 participants with generally low legume consumption), 14 crossover RCTs (448 participants), one parallel RCT and one non-randomized trial. Meta-analyses of cohort studies were suggestive of null associations for CVD, CHD, stroke and T2D. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference -0.22 mmol/L), low density lipoprotein (LDL)-cholesterol (-0.19 mmol/L), fasting glucose (-0.19 mmol/L), and HOMA-IR (-0.30). Heterogeneity was high (I2 = 52% for LDL-cholesterol, >75% for others). The overall evidence for associations between consumption of legumes and risk of CVD and T2D was considered limited - no conclusion. Conclusion: Legume consumption was not found to influence risk of CVD and T2D in healthy adult populations with generally low legume consumption. However, protective effects on risk factors, seen in RCTs, lend some support for recommending legume consumption as part of diverse and healthy dietary patterns for prevention of CVD and T2D.

Birth order, sibship size, and risk of atopic dermatitis, food allergy, and atopy: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis and food allergy are two frequently concomitant manifestations of the presence of atopy. A substantial number of studies have been published on the association of birth order and sibship size (number of siblings) with atopic dermatitis, food allergy, and atopy. The present work is the first systematic synthesis of the existing literature on this topic. METHODS: Fifteen databases were searched. Screening, data extraction, and quality assessment were performed by independent pairs. Comparable numerical data were statistically synthesized using random-effects robust variance estimation. RESULTS: In total, 114 studies were included out of 8819 papers obtained from database searches. Birth order ≥2 versus 1 was associated with lower risk of ever atopic dermatitis (pooled risk ratio [RR] 0.91, 95% CI 0.84-0.98), current food allergy (RR 0.77, 95% CI 0.66-0.90), and positive skin prick test (SPT) to common aeroallergens (RR 0.86, 95% CI 0.77-0.97). Sibship size ≥2 versus 1 was associated with decreased risk of current atopic dermatitis (RR 0.90, 95% CI 0.83-0.98), ever atopic dermatitis (RR 0.92, 95% CI 0.86-0.97), and positive SPT to common aeroallergens (RR 0.88, 95% CI 0.83-0.92). No putative associations were seen regarding atopy assessed through allergen-specific immunoglobulin E with common allergens. CONCLUSION: The presence of siblings and being second-born or later may decrease the lifetime risk of atopic dermatitis and food allergy, albeit marginally. Similar association was seen with SPT sensitization. However, significant protection was not found for IgE sensitization.

Antimicrobial stewardship in the era of the COVID-19 pandemic: A systematic review protocol on the opportunities and challenges for Sub-Saharan Africa.

BACKGROUND: Antimicrobial resistance (AMR) remains one of the leading threats to global public health and this may increase following COVID-19 pandemic. This is particularly the case in Africa where regulations on antimicrobial usage are weak. This protocol outlines the steps to undertake a systematic review to synthesize evidence on drivers of AMR and evaluate existing approaches to strengthening antimicrobial stewardship (AMS) programs in Sub-Saharan Africa (SSA). On the basis of the evidence generated from the evidence synthesis, the overarching goal of this work is to provide recommendations to support best practices in AMS implementation in SSA. METHODS: A systematic search will be conducted using the following databases: Global Health Library, PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, Google Scholar, Global Health, Embase, African Journals Online Library, Web of Science, antimicrobial databases (WHO COVID-19, TrACSS, NDARO, and JPIAMR), and the Cochrane databases for systematic reviews. Studies will be included if they assess AMR and AMS in SSA from January 2000 to January 31, 2023. RESULTS: The primary outcomes will include the drivers of AMR and approaches to AMS implementation in SSA. The Preferred Reporting Items for Systematic Reviews and Meta-analyses will guide the reporting of this systematic review. CONCLUSIONS: The findings are expected to provide evidence on best practices and resource sharing for policy consideration to healthcare providers and other stakeholders both at the local and international levels. Additionally, the study seeks to establish drivers specific to AMR during the COVID-19 era in the SSA, for example, with the observed increasing trend of antimicrobial misuse during the first or second year of the pandemic may provide valuable insights for policy recommendation in preparedness and response measures to future pandemics. PROSPERO REGISTRATION NUMBER: CRD42022368853.

Dietary fiber and growth, iron status and bowel function in children 0-5 years old: a systematic review.

Background: While dietary fiber intake is low in many children, the current trend to plant-based diets is associated with higher fiber intake in children raised on these diets. As older reports indicate that diets providing high fiber intake in children 0-5 years may affect growth, iron status and bowel function, we summarized the available evidence in this systematic review. Objective: To identify, critically appraise, and synthesize evidence on the effect of high fiber intake on growth, iron and bowel function in children 0-5 years, with relevance to the Nordic and Baltic countries. Methods: Following a pre-registered protocol, we searched MEDLINE, EMBASE, Cochrane Central of Controlled Trials, and Scopus for clinical trials and prospective cohort studies published until November 2021. Two reviewers independently screened retrieved literature, extracted relevant data, and performed risk of bias assessment. Outcomes were growth, iron metabolism and bowel function in children 0-5 years. We narratively described findings from studies that met inclusion criteria. Results: From 5,644 identified records, five articles met the inclusion criteria. Two RCTs had an overall moderate risk of bias, while the three observational studies had serious risk. Overall, we found no robust association between high intake of dietary fiber and growth. In the RCTs, higher intake of fiber had a positive effect on bowel movements and constipation. No studies on fiber intake and iron status were identified.The certainty of the overall evidence was inconclusive for growth and bowel function, while no assessment was made for iron status. Conclusion: We found no clear association between high intake of dietary fiber and growth or bowel function in young children living in affluent countries, albeit with only a limited number of studies. There is a lack of studies investigating health effects of high fiber intake in small children.

Animal versus plant-based protein and risk of cardiovascular disease and type 2 diabetes: a systematic review of randomized controlled trials and prospective cohort studies.

Objectives: To systematically review the evidence on the effect of replacing the intake of animal protein with plant protein on cardiovascular disease (CVD) and type 2 diabetes (T2D) and their intermediate risk factors. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 12th May 2022 for randomized controlled trials (RCTs) or prospective cohort studies that investigated replacement of animal protein with plant protein from foods. Outcomes were CVDs, T2D, and in RCTs also the effects on blood lipids, glycemic markers, and blood pressure. Risk of bias was evaluated with the Cochrane's RoB2, ROBINS-I, and USDA's RoB-NObS tools. Random-effects meta-analyses assessed the effects of plant vs. animal proteins on blood lipids in RCTs. The evidence was appraised according to the World Cancer Research Fund's criteria. Results: After screening 15,090 titles/abstracts, full text of 124 papers was scrutinized in detail, from which 13 RCTs and seven cohort studies were included. Eight of the RCTs had either some concern or high risk of bias, while the corresponding evaluation of cohort studies resulted in moderate risk of bias for all seven. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference -0.11 mmol/L; 95% CI -0.22, -0.01) and low-density lipoprotein cholesterol (-0.14 mmol/L; 95% CI -0.25, -0.02) by replacing animal protein with plant protein. The substitution of animal protein with plant protein (percentage of energy intake) in cohort studies was associated with lower CVD mortality (n = 4) and lower T2D incidence (n = 2). The evidence was considered limited-suggestive for both outcomes. Conclusion: Evidence that the substitution of animal protein with plant protein reduces risk of both CVD mortality and T2D incidence is limited-suggestive. Replacing animal protein with plant protein for aspects of sustainability may also be a public health strategy to lower the risk of CVD mortality and T2D.