World Health Organization Reference Research Articles

SARS-CoV-2 Vaccine Effects on Semen Parameters: A Systematic Review and Meta-Analysis.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitomizes the best preventative SARS-CoV-2 infection strategy to counteract the severe consequences of infection. However, concerns have been raised that the vaccines could have an adverse effect on sperm function and overall reproductive health. This combined systematic review and meta-analysis aimed to investigate the effects of different available SARS-CoV-2 vaccines on semen parameters. A systematic PubMed, Scopus, Google Scholar, ScienceDirect, LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), and Scilit database literature search until mid-June 2022 was conducted. Prospective and retrospective studies were eligible. No limitation was placed on language. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were thereafter obtained. Upon search completion, 122 studies were identified and retrieved and 110 were excluded, while the remaining 12 independent studies evaluating the effects of coronavirus disease 2019 (COVID-19) vaccines on semen parameters were included in this review. The total number of men included was 1551, aged 22.4-48 years. Following meta-analysis, the SMD summary measure with 95% CI for each semen parameter included a concentration of 0.22 (0-0.22); Total sperm count of 0.11 (0.18-0.24); Total motility of 0.02 (0.05-0.09); Volume of 0.02 (-0.1-0.14); Vitality of 0.55 (-0.19-0.29), progressive motility of -0.43 (-0.54 to -0.32); Total motile sperm count of -0.38 (-0.44 to -0.31); And normal morphology of 0.42 (-0.54 to -0.3). In brief, the total sperm count was slightly increased post-vaccination, while progressive motility, total motile sperm count, and normal morphology were marginally reduced post-vaccination, according to the meta-analysis. No effects were observed regarding sperm viability and semen volume since the results of all the studies crossed the line of no effect. All seminal parameters analyzed showed a negligible or small change in relation to the vaccination effect. Furthermore, the parameters remained within the normal World Health Organization reference ranges, making the clinical significance unclear. Therefore, based on these results, it appears that vaccination does not have negative effects on semen quality. The individual study findings suggested that COVID-19 vaccines are not associated with decreased semen parameters.

Prevalence of weight status and associated factors of underweight among the medical students in Iran

Background: Increasing weight abnormalities among university students is a challenging problem around the world. Published studies most researched overweight/obesity and its contributing variables in this population. However, underweight can threat health and wellbeing of the students during academic period. The Objective of the present study was to investigate the prevalence of weight status and to explore associated factors of underweight among the students from Yasuj University of Medical Sciences. Methods: In a cross-sectional study, a random sample including 455 students were recruited from Yasuj University of Medical Sciences, Iran, during 2018-2019. Academic, socio-demographic and anthropometric characteristics of the students were gathered through a structured questionnaire. Body mass index was determined and classified according to the World Health Organization reference. Descriptive statistics were used to summarize data in numbers and percentages. The relationships of students’ characteristics with their weight status were checked using Chi-square test. Factors associated with underweight occurrence in students were detected by analyzing multiple binary logistic regression model and adjusted odds ratio. Result: Of the total participated students 87.5% were 19-24 years old and 66.2% were female. The mean ± standard deviation of students’ weight and BMI were 61.42±11.51and 22.14±3.36, respectively. The prevalence of underweight, normal weight and overweight/obesity among students were 15%, 66.15 and 18.9%, respectively. Among the considered variables, age (OR: 0.78 95% CI: 0.63,0.97), gender (OR:2.o8 95% CI: 1.o8, 3.99), number of educational term (OR:1.25, 95% CI: 1.06, 1.47) and father’s occupation (Or:2.13 95% CI:1.14, 3.99) were significantly associated with the underweight occurrence in students. Conclusion. The prevalence of underweight and overweight/obesity among studied university students were high. The younger students, female students, students at higher number of educational term and students with fathers not an employee were at higher risk of being underweight. Suitable programs to promote healthy diets and practices among university students must be provided.

Estimating annual effective dose and excess of the lung risk factor of radon gas in University of Al-Hamdaniya buildings

Radioactive radon gas is a source of environmental pollution, especially in places where radon levels are high. Radon gas concentrations must be kept at their lowest levels and below globally acceptable limits for a safe environment, which can be accomplished by taking frequent measurements to identify and fix high concentration areas. In this study, radon gas concentration was measured in the air of several buildings of the University of Al-Hamdaniya using the CR-39 solid state nuclear track detector. The measured radon concentrations ranged from 19.24 to 64.60 Bq.m−3, with an average of 41.54 Bq.m−3. The effective annual dose ranged from 0.48 to 1.62 mSv/y. The lifetime cancer risk was 1.86 × 10−3 to 6.26 × 10−3. The mean radon concentration obtained was less than the World Health Organization reference level of 100 Bq.m−3.

Nutritional status and growth centiles using anthropometric measures of school-aged children and adolescents from Multan district

BackgroundNutritional status among children and adolescents is assessed using growth rates. The aim of this study was to assess age- and gender-specific height, weight, and body mass index (BMI) centiles among children and adolescents relative to World Health Organization (WHO) references. MethodsA sample of 1040 school-aged children and adolescents aged 3–18 years from Multan District in Pakistan were selected for the study between January and March 2020. Multistage stratified random sampling was used for sample selection. Centile curves of height, weight, and BMI for age and gender were obtained using the lambda-mu-sigma (LMS) method, and results were compared with WHO 2007 references. ResultsFor boys and girls, the average height was 137.37 ± 8.24 and 135.62 ± 9.64 cm, average weight was 36.32 ± 6.84 and 35.21 ± 7.27 kg, and average BMI was 18.44 ± 2.67 and 18.36 ± 2.91, respectively. The height centiles of boys were higher than the WHO reference, and during the prepubertal period (age 8 years or older) the centiles were lower than the WHO reference. The height centiles of girls were higher than the WHO reference, and during the pubertal period (age 10 years or older) the centiles were lower than the WHO reference. The gender-wise BMI centiles were higher compared to the WHO reference. ConclusionThe prevalence of thinness, overweight, and obesity in boys and girls was significantly higher than the WHO reference. The results of this study on centiles are up-to-date and will be used as a standard for comparison.

BMI status relative to international and national growth references among Pakistani school-age girls

BackgroundA sizable proportion of school-going children from developing countries has abnormal growth parameters, often not standardized with international reference values. We aimed to assess the prevalence of underweight, overweight, and obesity in the schoolgirls of Punjab according to international and local references.MethodsIn this population-based cross-sectional study, 10,050 school-going girls aged 8–16 years from 12 districts of northern, central, and southern Punjab were recruited. Estimates of normal weight, underweight, overweight and obesity were calculated in the girls according to three international BMI references including centers for disease control (CDC) 2000, the international obesity task force (IOTF) 2012 and world health organisation (WHO) 2007 in addition to a local reference for the population under study. We used Cohen’s kappa statistics to analyse the agreement of our data with reference values.ResultsThere was marked overestimation of underweight (23.9%, 14.5%, 15.2% and 4.37%), slight underestimation of overweight (5.3%, 7.3%, 7.9% and 8.97%) and moderate underestimation of obesity (1.9%, 1.5%, 2.2% and 5.67%) according to CDC, IOTF, WHO and local reference, respectively. When the weight status of the study cohort was compared with the local data, we found comparable results in all four weight categories.ConclusionWe recommend population-wide further studies to estimate the prevalence of weight status in school-age girls for devising appropriate references and for planning strategies for public health policy and management.

An improved HIV antigen/antibody prototype assay for earlier detection of acute HIV infection.

Early detection of acute HIV infection by HIV antigen/antibody assays depends on antigen sensitivity. Maintaining consistently high sensitivity across diverse HIV strains is critical to ensure equal detection. The performance of an improved HIV antigen/antibody prototype, HIV Combo Next, was evaluated for detection of genetically-diverse HIV strains and seroconversion samples. Antigen sensitivity of the prototype was evaluated and compared to five FDA-approved HIV antigen/antibody assays using World Health Organization (WHO) HIV p24 antigen standard and reference panels, 17 virus isolates and 9 seroconversion panels. Antibody sensitivity and assay specificity of the prototype were also assessed with 1062 disease-staged and genotyped samples, and samples from 3000 blood donors and 955 individuals with low-risk for HIV infection. Compared with other assays evaluated, the prototype demonstrated the best analytical sensitivity for WHO antigen standard, reference panels including 12 HIV-1 variants (0.04 - 0.25 IU/ml) and one HIV-2 variant, and 17 HIV virus isolates including HIV-1 group M, N, P and O and HIV-2 (0.3 -16 pg/ml). The enhanced sensitivity was also observed for seroconversion samples, detecting more PCR-positive samples with detection up to 7 days earlier than the other assays. Improvement in antigen sensitivity did not compromise antibody sensitivity or assay specificity, detecting all HIV disease-staged and genotyped samples, with assay specificity of 99.97% for blood donors and 99.68% for the low-risk population. These data indicate that the new prototype HIV Combo Next assay will be of diagnostic value, providing improved early detection for acute HIV infection from divergent HIV strains.

Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis?

Research questionDoes Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? DesignA prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1–2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. ResultsThe interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 × 106/ml, with only a single participant (1.3%) with a sperm count of 12.5 × 106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. ConclusionsThe semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

Assessment of analytical bias in ferritin assays and impact on functional reference limits

Serum ferritin is currently the recommended laboratory test to investigate iron deficiency. There have been efforts to standardise serum ferritin assays with implementation of traceability to the World Health Organization reference standard. We evaluate the analytical bias among five widely used commercial ferritin assays in Australia. The relationship between serum ferritin and erythrocyte parameters was recently explored to derive functional reference limits. Residual patient serum specimens were analysed by five participating laboratories that utilised a different ferritin assay, Abbott, Beckman Coulter, Roche, Siemens, and Ortho. Using data mining approach, functional reference limits for Siemens, Abbott, and Ortho serum ferritin methods were derived and compared. At clinically relevant ferritin decision points, compared to the Beckman method, the Roche assay showed higher results ranging from 6 μg/L (31%) at the lowest decision point to 575 μg/L (57%) at the highest decision point. In contrast, the Ortho method underestimated ferritin results at lower decision points of 20 and 30 μg/L, with estimated ferritin results of 16 μg/L (-19%) and 27 μg/L (-12%), respectively. The Abbott and Siemens assays showed a positive bias which was introduced at differing decision points. The comparison of the Siemens and Ortho methods presents similar inflection points between the two assays in the establishment of functional reference limits for serum ferritin. There remain significant biases among some of the commonly used commercial ferritin assays in Australia. More studies are needed to assess if functional reference limits are a way to overcome method commutability issues.

Low-dose Methotrexate Therapy Does Not Affect Semen Parameters and Sperm DNA.

Methotrexate is widely used in inflammatory diseases during the patients' reproductive years. The effect on male fertility and sperm DNA integrity is largely unknown. We evaluated sperm DNA integrity and basic semen parameters according to the World Health Organization (WHO) in male patients with inflammatory diseases treated with methotrexate. Semen samples from 14 patients on low-dose maintenance methotrexate were compared with samples from 40 healthy volunteers. Further, 5 patients delivered samples on and off methotrexate therapy for paired comparison. Sperm DNA fragmentation index (DFI), concentration, motility, and morphology were evaluated. Blood sex hormones and methotrexate levels were measured in blood and semen. DNA fragmentation index in methotrexate-treated patients was comparable with that in healthy volunteers (DFI, 11.5 vs 15.0; P = .06), and DFI did not change significantly on and off methotrexate in the paired samples (DFI, 12.0 vs 14.0; P = 0.35). Sperm concentration, motility, and morphology did not differ between men treated with methotrexate and healthy volunteers. Sperm progressive motility increased off therapy compared with on therapy (65.0% vs 45.0%, P = .04), but all fluctuations in progressive motility were within the WHO reference interval. All methotrexate polyglutamates1-5 were detected in blood, but only methotrexate polyglutamate1 in semen. Serum testosterone was unaffected by methotrexate therapy. Patients treated with low-dose methotrexate have a sperm quality comparable with that of healthy volunteers, and methotrexate treatment does not increase sperm DNA fragmentation. This study does not support cryopreservation of semen before treatment initiation nor a 3-month methotrexate-free interval prior to conception.

The association between overweight and obesity on bone mineral density in 12 to 15 years old adolescents in China.

Overweight/obesity can influence bone mineral accretion, but the conclusions are not consistent. We aimed to examine the association between bone mineral density (BMD) levels and body mass index (BMI) in 12 to 15 years old adolescents.We performed a cross-sectional study including 8365 adolescents. BMD was evaluated using a quantitative ultrasound device. Z scores for BMI were evaluated using World Health Organization references. Logistic regression models were performed to evaluate the association between BMD levels and BMI.Totally 1866 (22.3%) adolescents had low /reduced BMD, and boys had a higher rate than girls (72.6% vs 27.4%, P < .001). The rates of thinness, normal weight, overweight, and obesity were 2.8%, 57.1%, 22.3%, and 17.8%, respectively. The multivariable-adjusted (age, sex, systolic blood pressure, and height Z score) ORs (95% CIs) of low/reduced BMD associated with BMI groups (thinness, normal [reference], overweight, and obesity) were 0.59 (0.39–0.89), 1.00, 1.61 (1.41–1.84), and 1.98 (1.69–2.30), respectively (Ptrend < .001). This positive association existed in boys and girls though the differences were not significant between normal weight and thin girls. The multivariable-adjusted ORs for each 1-unit increase in BMI Z score were 1.36 (1.24–1.49) for girls, and 1.23 (1.16–1.30) for boys, and 1.26 (1.20–1.32) for all participants.We observed a positive association between BMI and low/reduced BMD in 12 to 15 years old adolescents. More attention should be paid on overweight and obese adolescents to reduce the risk of low BMD. Further studies are needed to explore the mechanisms of this association.

O-040 The evolution of WHO Manual. Where are we now?

Abstract text Male factor infertility is associated with impaired overall health, decreased life expectancy, lower quality of life and may affect reproductive outcomes even under assisted reproductive technology (ART) settings. Male factors, alone or combined with female factors, contribute to at least 50% of reported infertility cases. Despite this, the male partner is often overlooked in the evaluation and treatment of infertility. A routine semen analysis is frequently the only test carried out to assess a man’s fertility potential. The state-of-art on how the human semen should be assessed is provided by the World Health Organization (WHO), which periodically releases manuals that include specific protocols and reference standards. These manuals include detailed laboratory methods for semen examination, protocols for sperm preparation and cryopreservation, quality assurance and quality control, results’ interpretation, and reference ranges. Unlike the previous four versions, the latest 2010 WHO reference values relied on clinical chemistry principles to generate 95% intervals for sperm volume, count, motility, vitality, and morphology from recent fathers. The fifth centile was deemed suitable for representing semen characteristics at lower limits. The reference values ultimately obtained were markedly lower than those previously reported, raising concerns about its clinical utility and generalizability. Criticisms included the limited geographical area of patients analyzed, the methods used for semen evaluation, and the potential impact of the new reference range on patient referral, diagnosis, and treatment guidance. An updated new WHO manual (6th edition) is about to be released with much expectation. Although semen analysis remains one of the cornerstones of the infertility evaluation, a male infertility workup primarily based on routine semen analysis does not provide men with an optimal fertility pathway for many reasons. First, reference intervals do not reliably distinguish fertile from subfertile subjects. Second, an individual patient’s results have limited prognostic value for both natural and assisted conception unless at extreme lower limits. Third, there is a wide variation in how laboratories perform a semen analysis. Lastly, routine semen analysis does not detect sperm DNA defects that might adversely impact embryo development, implantation, and offspring’s health. Guidelines issued by professional societies recommend that a full andrological assessment be performed in all men with couple infertility. Well-trained reproductive urologists or clinical andrologists should perform the male evaluation, including a detailed history, physical examination, semen analysis, endocrine assessment, and other tests as needed. Therefore, the importance of WHO manuals remains critical. However, the goals of a comprehensive male infertility workup go beyond the laboratory assessment of human semen. It comprises i. Diagnosis, i.e., detection of any underlying relevant medical or lifestyle conditions potentially impairing the (reproductive) health of the male or his offspring; ii. Counselling, particularly regarding the impact of infertility, genetic factors, age, and lifestyle on pregnancy prospects, reproductive and overall health, and offspring’s well-being; and iii. Management Guidance, i.e., identifying optimal treatment options to improve the likelihood of achieving natural pregnancy or ART success. The prevention and management of male infertility are integral components of comprehensive sexual and reproductive health services needed to attain a sustainable development goal.

Water quality assessment and geochemical processes in the unconfined coastal Boa Viagem Aquifer, Recife, NE Brazil

A hydrochemical study was conducted on the Quaternary Aquifer, in Recife, Brazil. Groundwater samples were collected in March–April 2015, at the beginning of the rainy season. Conventional graphics, ionic ratios, saturation indices, GIS mapping, and geostatistical and multivariate statistical analyses were used to water quality assessment and to characterize the main hydrochemical processes controlling groundwater’s chemistry. Q-mode hierarchical cluster analysis separated the samples into three clusters and five sub-clusters according to their hydrochemical similarities and facies. Principal Component Analysis (PCA) was employed to the studied groundwater samples where a three-factor model explains 80% of the total variation within the dataset. The PCA results revealed the influence of seawater intrusion, water-rock interaction, and nitrate contamination. The physico-chemical parameters of ~30% groundwaters exceed the World Health Organization (WHO) guidelines for drinking water quality. Nitrate was found at a concentration &gt;10 mg NO3−/L in ~21% of the wells and exceeded WHO reference values in one. The integrated approach indicates the occurrence of the main major hydrogeochemical processes occurring in the shallow marine to alluvial aquifer as follow: 1) progressive freshening of remaining paleo-seawater accompanying cation exchange on fine sediments, 2) water-rock interaction (i.e., dissolution of silicates), and 3) point and diffuse wastewater contamination, and sulfate dissolution. This study successfully highlights the use of classical geochemical methods, GIS techniques, and multivariate statistical analyses (hierarchical cluster and principal component analyses) as complementary tools to understand hydrogeochemical processes and their influence on groundwater quality status to management actions, which could be used in similar alluvial coastal aquifers.

Descriptive Study about Bodyweight Status of Extremadura Adolescents. Are We Applying the Best Indicator as the Reference Parameter?

Simple SummaryThere are no agreed criteria that establish childhood obesity thresholds, based on BMI, which may be used to diagnose overweight/obesity in adolescents. This tool has been determined as the most practical and least costly method in classifying bodyweight status in adolescents. However, it is an indicator of bodyweight, and not fat mass. This study assessed and compared bodyweight status of Extremadura adolescents by sex and age using international (World Health Organization), national (Faustino Obergozo Foundation), and regional references (Extremadura). A single-measure descriptive study (bodyweight and height) was conducted in 4130 adolescents aged between 12–17 years. BMI was calculated to classify participants in the bodyweight categories. The WHO criteria classified 542 individuals in a different category compared to FO, and 1028 individuals with respect to EX. Moreover, FO classified 684 adolescents in a different category than EX. Despite the concordance in diagnostic overweight/obesity observed when comparing the three classifications, differences in percentage of participants for each category were found in all pairwise comparisons (WHO–FO, WHO–EX, and FO–EX). Thus, WHO, FO, and EX criteria differ when estimating overweight/obesity prevalence in adolescents, being able to fall into a wrong diagnosis of overweight or obese.Background: There is no agreed criteria that establishes childhood obesity thresholds based on BMI, which may be used to assess adolescent overweight/obesity. This tool has been determined at the most practical and least costly in classifying bodyweight status in adolescents. However, it is an indicator of bodyweight and not adiposity. Aims: To assess bodyweight status of Extremadura adolescents by sex and age using international, national, and regional reference criteria and comparing the different diagnoses criteria. Methods: A descriptive cross-sectional study was conducted with 4130 adolescents (12–17 years). Bodyweight and height were assessed. Results: Pairwise comparisons indicates that the World Health Organization (WHO) classified 542 individuals in a different category compared to Faustino Obergozo (FO), and 1028 individuals with respect to the Extremadura adolescents’ percentiles (EX). Moreover, FO classified 684 adolescents in a different category than EX. Despite the concordance in diagnostic criteria (by Cohen’s kappa test) reported between the WHO, FO, and EX for all bodyweight categories in both sexes and all age ranges, significant differences were found (assessed by Cochran Q test and McNemar test as post-hoc) between the WHO and FO for all bodyweight proportion except in the thinness category in girls (15–17 years) and boys (12–14 years). Meaningful differences were also obtained comparing WHO and EX for each bodyweight category in all ages and sexes. Comparisons between FO and EX revealed significant differences for all bodyweight categories in all participants except for overweight in girls (12–14 years) and boys (15–17 years) and normal weight and obesity in girls (15–17 years). Conclusions: the WHO, FO, and EX criteria present different outcomes estimating overweight and/or obesity prevalence in adolescents aged between 12 and 17 years. The change from Extremadura criteria to the WHO reference will result in more adolescents being diagnosed as overweight or obese.

The adherence to school meals is associated with a lower occurrence of obesity among Brazilian adolescents

This study aimed to verify the association between adherence to meals from the Brazilian National School Feeding Program (PNAE) and obesity indicators among adolescents. Data from 12,373 students attending public schools from the 2015 National Survey of School Health were used. Adherence to school meals was assessed using a self-administered questionnaire and classified as null (zero/rarely), low (1-2×/week), moderate (3-4×/week), and high (5×/week). Weight and height were measured and classified based on the World Health Organization's reference for Z-scores of body mass index (BMI) for age, overweight (≥ + 1 Z-score) and obesity (≥ + 2 Z-score). Linear and Poisson regression models adjusted for potential confounding factors (gender, race/ethnicity, age, region, goods score, maternal education, living with parents, eating outside of school profile and physical activity) were performed to assess the association between adherence to school meals and the indicators (Z-score, overweight and obesity). The prevalence of high adherence was 21.6% and obesity, 8%. An inverse and dose-response association were observed between adherence to the PNAE meals and obesity indicators. Adolescents with high adherence to school meals (5×/week) had a 0.10 lower BMI Z-score (coefficient = −0.10, CI -0.17;-0.03), 11% less prevalence of overweight (PR = 0.89, CI 0.80;0.99) and 24% less prevalence of obesity (PR = 0.76, CI 0.62;0.93) than those with a lower adherence (<5×/week). Our results showed that the adherence to PNAE meals may contribute to obesity prevention in Brazil.

A first WHO reference reagent for the detection of anti-human platelet antigen-15b.

Background and ObjectivesAlloantibodies to human platelet antigen‐15b (anti‐HPA‐15b) have been detected in mothers with foetal–neonatal alloimmune thrombocytopenia and in multiply transfused patients. Assays used to detect this antibody, which aids in disease diagnosis, can be unreliable and vary in sensitivity. The objective was to generate a stable, lyophilized anti‐HPA‐15b preparation and evaluate its suitability as a World Health Organization (WHO) reference reagent for use in the quality control of platelet alloantibody detection assays. Results from an international collaborative study to evaluate the preparation were used to assign a minimum potency at which laboratories can be expected to detect the antibody.Materials and MethodsRecalcified plasma containing anti‐HPA‐15b was aliquotted, lyophilized and coded 18/220. Twenty‐five laboratories in 16 countries tested doubling dilutions of the reconstituted material in glycoprotein‐specific assays such as the monoclonal antibody–specific immobilization of platelet antigen assay and reported the last positive (or endpoint) dilution.ResultsTwenty‐four laboratories (96%) detected antibodies with HPA‐15b specificity in preparation 18/220. Reported endpoint dilutions were normally distributed with a modal dilution of 1 in 16 and ranged from 1 in 2 to 1 in 128. Only two laboratories (8%) failed to detect anti‐HPA‐15b at 1 in 8 dilution.ConclusionsWhen diluted 1 in 8, most laboratories detected anti‐HPA‐15b in preparation 18/220 using HPA‐15bb platelets but not with HPA‐15aa platelets. The participants agreed this to be an appropriate dilution for assignment as the minimum potency. In October 2020, the WHO Expert Committee on Biological Standardization approved 18/220 as an International Reference Reagent.

Trend and Causes of Overweight and Obesity among Pre-School Children in Kuwait.

Identifying life risk factors of obesity early will help inform policymakers to design evidence-based interventions. The following study aims to assess the trend of overweight and obesity over four years among pre-school Kuwait children, and to examine their association with breakfast skipping (BF), sugary and sweetened beverage (SSB) consumption, and screen time. Children aged 2–5 years (n = 5304) were selected from 2016 to 2019 national surveys. Overweight and obesity were defined according to the World Health Organization references. The children’s mothers were asked about the BF of their children the day of the survey, their frequency of SSB consumption, and their weekly screen time use. Logistic regression was used to identify the risk factors associated with overweight/obesity. No significant decline (p values ≥ 0.12) was found for both overweight and obesity. Contrastingly, BF skipping, SSB consumption, and screen time declined (p < 0.0001). The BF skippers were found to have a 31% lower risk of being overweight. Daily TV watching, for 2–3 h, increases the odds of obesity by 5.6-fold. Our findings are encouraging regarding the decline in risky behaviours over time. However, more effort should be made both at the micro- and macro-level for a sustainable reduction in overweight and obesity.

Semen parameter thresholds and time-to-conception in subfertile couples: how high is high enough?

AbstractSTUDY QUESTIONWhat thresholds for total sperm count, sperm concentration, progressive motility, and total progressive motile sperm count (TPMC) are associated with earlier time-to-conception in couples undergoing fertility evaluation?SUMMARY ANSWERValues well above the World Health Organization (WHO) references for total sperm count, concentration, and progressive motility, and values up to 100 million for TPMC were consistently associated with earlier time-to-conception and higher conception rates.WHAT IS KNOWN ALREADYAlthough individual semen parameters are generally not able to distinguish between fertile and infertile men, they can provide clinically useful information on time-to-pregnancy for counseling patients seeking fertility treatment. Compared to the conventional semen parameters, TPMC might be a better index for evaluating the severity of male infertility.STUDY DESIGN, SIZE, DURATIONWe used data from a longitudinal cohort study on subfertile men from 2002 to 2017 and included 6061 men with initial semen analysis (SA) in the study.PARTICIPANTS/MATERIALS, SETTING, METHODSMen from subfertile couples who underwent a SA within the study period were included, and 5-year follow-up data were collected to capture conception data. Couples were further categorized into two subgroups: natural conception (n = 5126), after separating those who achieved conception using ART or IUI; natural conception without major female factor (n = 3753), after separating those with severe female factor infertility diagnoses. TPMC was calculated by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm (%). Cox proportional hazard models were used to report hazard ratios (HRs) with 95% CIs before and after adjusting for male age, the number of previous children before the first SA, and income. Using the regression tree method, we calculated thresholds for total sperm count, sperm concentration, progressive motility, and TPMC to best differentiate those who were more likely to conceive within 5 years after first SA from those less likely to conceive. We also plotted continuous values of semen parameters in predicting 5-year conception rates and time-to-conception.MAIN RESULTS AND THE ROLE OF CHANCEOverall, the median time to conception was 22 months (95% CI: 21–23). A total of 3957 (65%) couples were known to have achieved conception within 5 years of the first SA. These patients were younger and had higher values of sperm concentration, progressive motility, and TPMC. In the overall cohort, a TPMC of 50 million best differentiated men who were more likely to father a child within 5 years. Partners of men with TPMC ≥50 million had a 45% greater chance of conception within 5 years in the adjusted model (HR: 1.45; 95% CI: 1.34–1.58) and achieved pregnancy earlier compared to those men with TPMC &amp;lt; 50 million (median 19 months (95% CI: 18–20) versus 36 months (95% CI: 32–41)). Similar results were observed in the natural conception cohort. For the natural conception cohort without major female factor, the TPMC cut-off was 20 million. In the visual assessment of the graphs for the continuous semen parameter values, 5-year conception rates and time-to-conception consistently plateaued at higher values of sperm concentration, total sperm count, progressive motility, and TPMC compared to the WHO reference levels and our calculated thresholds. For TPMC, values up to 100–150 million were still associated with a better conception rate and time-to-conception in the visual assessment of the curves.LIMITATIONS, REASONS FOR CAUTIONThere was limited information on female partners and potential for inaccuracies in capturing less severe female infertility diagnoses. Also we lacked details on assisted pregnancies achieved outside of our healthcare network (with possible miscoding as ‘natural conception’ in our cohort). We only used the initial SA and sperm morphology, another potentially important parameter, was not included in the analyses. We had no information on continuity of pregnancy attempts/intention, which could affect the time-to-conception data. Finally, most couples had been attempting conception for &amp;gt;12 months prior to initiating fertility treatment, so it is likely that we are underestimating time to conception. Importantly, our data might lack the generalizability to other populations.WIDER IMPLICATIONS OF THE FINDINGSOur results suggest that a TPMC threshold of 50 million sperm provided the best predictive power to estimate earlier time-to-conception in couples evaluated for male factor infertility. Higher values of sperm count, concentration and progressive motility beyond the WHO references were still associated with better conception rates and time-to-conception. This provides an opportunity to optimize semen parameters in those with semen values that are low but not abnormal according to the WHO reference values. These data can be used to better inform patients regarding their chances of conception per year when SA results are used for patient counseling.STUDY FUNDING/COMPETING INTEREST(S)None.TRIAL REGISTRATION NUMBERN/A.

Non-drug therapies for the secondary prevention of lower limb muscle cramps.

Lower limb muscle cramps are common and painful. They can limit exercise participation, and reduce quality of sleep, and quality of life. Many interventions are available for lower limb cramps; some are controversial or could cause harm, and often, people experience no benefit from the interventions used. This is an update of a Cochrane Review first published in 2012. We updated the review to incorporate new evidence. To assess the effects of non-drug, non-invasive therapies for lower limb muscle cramps. In August 2018 and May 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of included studies. We imposed no restrictions by language or publication date. We included all randomised controlled trials (RCTs) of non-drug, non-invasive interventions tested over at least four weeks, for lower limb muscle cramps in any group of people, except pregnant women. The primary outcome was cramp frequency. Secondary outcomes were cramp pain severity, cramp duration, health-related quality of life, quality of sleep, participation in activities of daily living, proportion of participants reporting lower limb muscle cramps, and adverse events. Two review authors independently selected trials, assessed risk of bias, and cross-checked data extraction and analyses according to standard Cochrane procedures. We included three trials, with 201 participants, all 50 years of age and older; none had neurological disease. All trials evaluated a form of stretching for lower limb muscle cramps. A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps (measured on a 10 cm visual analogue scale (VAS) where 0 = no pain and 10 cm = worst pain imaginable) in people aged 55 years and older, compared to no intervention (mean difference (MD) -1.30, 95% confidence interval (CI) -1.74 to -0.86; 1 RCT, 80 participants; low-certainty evidence). The certainty of evidence was very low for cramp frequency (change in number of cramps per night from week zero to week six) comparing the stretching group and the no intervention group (MD -1.2, 95% CI -1.8 to -0.6; 80 participants; very low-certainty evidence). Calf stretching alone for 12 weeks may make little to no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older (stretching group median number of cramps in the last four weeks (Md) 4, interquartile range (IQR) 8; N = 48; sham stretching group Md 3, IQR 7.63; N = 46) (U = 973.5, z = -0.995, P = 0.32, r = 0.10; 1 RCT, 94 participants; low-certainty evidence). This trial did not report cramp severity. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome (N = 24). It was not possible to fully analyse the frequency data and the scale used to measure cramp severity is not validated. No study reported health-related quality of life, quality of sleep, or participation in activities of daily living. No participant in these three studies reported adverse events. The evidence for adverse events was of moderate certainty as the studies were too small to detect uncommon events. In two of the three studies, outcomes were at risk of recall bias, and tools used to measure outcomes were not validated. Due to limitations in study designs that led to risks of bias, and imprecise findings with wide CIs, we cannot be certain that findings of future studies will be similar to those presented in this review. A combination of daily calf and hamstring stretching for six weeks may reduce the severity of night-time lower limb muscle cramps in people aged 55 years and older, but the effect on cramp frequency is uncertain. Calf stretching alone compared to sham stretchingfor 12 weeks may make little or no difference to the frequency of night-time lower limb muscle cramps in people aged 60 years and older. The evidence is very uncertain about the effects of a combination of daily calf, quadriceps, and hamstring stretching on the frequency and severity of leg cramps in 50- to 60-year-old women with metabolic syndrome. Overall, use of unvalidated outcome measures and inconsistent diagnosticcriteriamake it difficult to compare the studies and apply findings to clinical practice. Given the prevalence and impact of lower limb muscle cramps, there is a pressing need to carefully evaluate many of the commonly recommended and emerging non-drug therapies in well-designed RCTs across all types of lower limb muscle cramps. A specific cramp outcome tool should be developed and validated for use in future research.

Preliminary hazard assessment of air pollution levels in Nizwa, Rusayl and Sur in Oman

The World Health Organization (WHO) recognises air pollution as a serious public health concern in many developing countries due to the influx of energy-intensive industries with limited planning and exposure mitigation strategies. Due to industrial expansion and release of associated air pollutants in Oman, the US Environmental Protection Agency human health risk assessment (HHRA) model was used to determine the non-carcinogenic hazard associated with exposure to industrial emissions. Across the three industrial cities (Nizwa, Sur and Rusayl), the study found ambient average concentrations (μg/m3) of 1 h carbon monoxide (CO) (606–1974), nitrogen dioxide (NO2) (7.7–43.9) and sulfur dioxide (SO2) (4.8–9.0) and 24 h PM2.5 (7.3–7.8) and PM10 (38.7–51.5) to be significantly lower than both the Ministry of Environment and Climatic Affairs (MECA) and WHO limits. The HHRA analysis showed that exposure to the air pollutants produced low non-carcinogenic adverse health effects, as the hazard quotient (HQ) was found to be &lt;1 among the population. However, there was an increase in HQ for WHO reference exposure level (REL) values compared with that of MECA; this is due to the relaxed/high REL limits of the latter. Future epidemiological studies involving long-term air pollution exposure assessment and health data may improve the reliability of the current HHRA estimates.

Anaemia Among Children Who Attended the Children's Teaching Hospital in Karbala, Iraq.

IntroductionThe World Health Organization (WHO) reported a moderate incidence of anaemia among pregnant and nonpregnant women and among children younger than 59 months in 2011.PurposeThe aim of this study was to investigate anaemia among children younger than 14 years submitted to haematological exams at the Children’s Teaching Hospital in Karbala, Iraq.Patients and MethodsThis was a cross-sectional study carried out in the Children’s Teaching Hospital Laboratory Department in Karbala, Iraq, from 1 July 2019 until 1 September 2019.ResultsThe prevalence of anaemia among children aged 0–14 years in Karbala was 9.9%. There was no significant relationship between the type of anaemia diagnosed and age or sex. However, there was a significantly positive relationship between the type of anaemia diagnosed and each ferritin level, mean corpuscular volume, and mean corpuscular haemoglobin (p<0.0001). The study participant skull diameter and length in relation to sex were compared to the WHO reference values for child growth standards, and the study values were less than the normal range for children below 5 years of age.ConclusionA high prevalence of anaemia among children was reported with its apparent consequence on their health. This study highlights the prevalence of anaemia among children up to 14 years of age in Karbala, and future research is encouraged.