The impact of primary headaches on disability outcomes: a literature review and meta-analysis to inform future iterations of the Global Burden of Disease study.

BACKGROUND: The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0-1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients' disability which might inform future GBD definitions of DW for headache disorders. METHODS: We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females' percentage in the sample, and age). We developed a 0-1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium. RESULTS: A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake. CONCLUSIONS: Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.

Prevalence of unmet health care need in older adults in 83 countries: measuring progressing towards universal health coverage in the context of global population ageing.

Current measures for monitoring progress towards universal health coverage (UHC) do not adequately account for populations that do not have the same level of access to quality care services and/or financial protection to cover health expenses for when care is accessed. This gap in accounting for unmet health care needs may contribute to underutilization of needed services or widening inequalities. Asking people whether or not their needs for health care have been met, as part of a household survey, is a pragmatic way of capturing this information. This analysis examined responses to self-reported questions about unmet need asked as part of 17 health, social and economic surveys conducted between 2001 and 2019, representing 83 low-, middle- and high-income countries. Noting the large variation in questions and response categories, the results point to low levels (less than 2%) of unmet need reported in adults aged 60+ years in countries like Andorra, Qatar, Republic of Korea, Slovenia, Thailand and Viet Nam to rates of over 50% in Georgia, Haiti, Morocco, Rwanda, and Zimbabwe. While unique, these estimates are likely underestimates, and do not begin to address issues of poor quality of care as a barrier or contributing to unmet need in those who were able to access care. Monitoring progress towards UHC will need to incorporate estimates of unmet need if we are to reach universality and reduce health inequalities in older populations.

Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis From the Global Burden of Disease Study 2019.

Objectives: We explored temporal variations in disease burden of ambient particulate matter 2.5 µm or less in diameter (PM2.5) and ozone in Italy using estimates from the Global Burden of Disease Study 2019. Methods: We compared temporal changes and percent variations (95% Uncertainty Intervals [95% UI]) in rates of disability adjusted life years (DALYs), years of life lost, years lived with disability and mortality from 1990 to 2019, and variations in pollutant-attributable burden with those in the overall burden of each PM2.5- and ozone-related disease. Results: In 2019, 467,000 DALYs (95% UI: 371,000, 570,000) were attributable to PM2.5 and 39,600 (95% UI: 18,300, 61,500) to ozone. The crude DALY rate attributable to PM2.5 decreased by 47.9% (95% UI: 10.3, 65.4) from 1990 to 2019. For ozone, it declined by 37.0% (95% UI: 28.9, 44.5) during 1990-2010, but it increased by 44.8% (95% UI: 35.5, 56.3) during 2010-2019. Age-standardized rates declined more than crude ones. Conclusion: In Italy, the burden of ambient PM2.5 (but not of ozone) significantly decreased, even in concurrence with population ageing. Results suggest a positive impact of air quality regulations, fostering further regulatory efforts.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

Investigating the Relationship between Parental Education, Asthma and Rhinitis in Children Using Path Analysis.

Parental socioeconomic position (SEP) is a known determinant of a child's health. We aimed to investigate whether a low parental education, as proxy of SEP, has a direct effect on physician-diagnosed asthma, current asthma and current allergic rhinitis in children, or whether associations are mediated by exposure to other personal or environmental risk factors. This study was a secondary data analysis of two cross-sectional studies conducted in Italy in 2006. Data from 2687 adolescents (10-14 years) were analyzed by a path analysis model using generalized structural equation modelling. Significant direct effects were found between parental education and family characteristics (number of children (coefficient = 0.6229, p < 0.001) and crowding index (1.1263, p < 0.001)) as well as with exposure to passive smoke: during pregnancy (maternal: 0.4697, p < 0.001; paternal: 0.4854, p < 0.001), during the first two years of children's life (0.5897, p < 0.001) and currently (0.6998, p < 0.001). An indirect effect of parental education was found on physician-diagnosed asthma in children mediated by maternal smoking during pregnancy (0.2350, p < 0.05) and on current allergic rhinitis mediated by early environmental tobacco smoke (0.2002; p < 0.05). These results suggest the importance of promotion of ad-hoc health policies for promoting smoking cessation, especially during pregnancy.

Methodological considerations in injury burden of disease studies across Europe: a systematic literature review.

BACKGROUND: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. METHODS: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. RESULTS: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. CONCLUSIONS: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.

Social Network and Environment as Determinants of Disability and Quality of Life in Aging: Results From an Italian Study.

Background: The increase in life expectancy is leading to a worldwide increase in chronic diseases and disability, with significant concern about their management and long-term care. Investigating the aging process using a bio-psychosocial perspective is essential to understanding how to reduce disability and improve the quality of life of aging people. This study aims to explore the role of social networks and built environment as predictors of disability and quality of life in the Italian population aged over 50 years. Materials and Methods: The research protocol is composed of several tools: World Health Organization Disability Assessment Scale 2.0 (WHODAS 2.0), World Health Organization Quality of Life Assessment in Aging (WHOQOL-AGE), Social Network Index (SNI), the Courage Built Environment Self-Reported Questionnaire (CBE-SR), and collection of sociodemographic information and information on health system coverage. Results: A total of 431 people were administered the protocol, and among them, 209 were males and 222 were females, with a mean age of 70 years. The majority of the sample reported earning a middle or high school diploma, and 60.6% of the sample declared to have a good health status. The results showed that people with a good social support network have higher levels of functioning and quality of life. However, the built environment did not significantly predict either disability or quality of life. Conclusions: These results could provide elements for dialogue with institutions and policymakers. This is fundamental to develop active policies aimed at the implementation of services and systems to promote healthy aging process.

Rules and ward climate in acute psychiatric setting: Comparison of staff and patient perceptions.

The ward climate or atmosphere refers to its material, emotional and social conditions. A good ward climate in psychiatric settings can influence the mood, behaviour and self-concept of patients and staff members and improve patient outcomes. Many studies have examined the relationship between ward climate and aggression, but only a few have investigated the effect of a ward's environment, rules and activities. This multicentric observational study aimed to assess the relationship between the rules/activities and the climate of four acute psychiatric units of Northern Italy. The Essen Climate Evaluation Scheme (EssenCES) questionnaire, which was administered to patients and staff, was used to evaluate the different dimensions of ward atmosphere. There was a good response rate (79%) in patients and staff members who completed the questionnaire (114 patients and 109 staff). Safety perception appeared to be quite different in patients and staff. The patients who were authorized to have more visiting hours and more time to use their mobile phone had higher scores on Experienced Safety subscale. A negative correlation between the Therapeutic Hold and Experienced Safety subscales was found in the staff members, and this was due to their negative perception. The ward climate seemed to be affected by the unit's rules, especially with respect to visits and the smartphones use. Nurses need to be aware of the importance of ward climate and how their own perception may differ from and that of patients: this gap could lead to decisions detached from the patients' needs.

Time of onset and/or diagnosis of ADHD in European children: a systematic review.

BACKGROUND: Attention-Deficit/ Hyperactivity Disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Symptoms related to this disorder cause a significant impairment in school tasks and in the activities of children's daily lives; an early diagnosis and appropriate treatment could almost certainly help improve their outcomes. The current study, part of the Models Of Child Health Appraised (MOCHA) project, aims to explore the age at which children experience the onset or diagnosis of ADHD in European countries. METHODS: A systematic review was done examining the studies reporting the age of onset/diagnosis (AO/AD) of ADHD in European countries (28 European Member States plus 2 European Economic Area countries), published between January 1, 2010 and December 31, 2019. Of the 2276 identified studies, 44 met all the predefined criteria and were included in the review. RESULTS: The lowest mean AO in the children diagnosed with ADHD alone was 2.25 years and the highest was 7.5 years. It was 15.3 years in the children with ADHD and disruptive behaviour disorder. The mean AD ranges between 6.2 and 18.1 years. CONCLUSIONS: Our findings indicate that there is a wide variability in both the AO and AD of ADHD, and a too large distance between AO and AD. Since studies in the literature suggest that an early identification of ADHD symptoms may facilitate early referral and treatment, it would be important to understand the underlying reasons behind the wide variability found. TRIAL REGISTRATION: PROSPERO registration: CRD42017070631 .

Quality of child healthcare in European countries: common measures across international databases and national agencies.

BACKGROUND: The evaluation of child healthcare is not yet widely explored, especially from a cross-country comparison perspective. The routine adoption of measures by national assessment agencies is under-investigated. Though the guiding principles developed at international level call for a child-centric multi-dimensional evaluation of child care, its feasibility is hampered by the availability of robust and harmonized data. METHODS: To explore the data availability, international databases (IDBs) were scrutinized and measures dealing with child health-related issues were collated. In parallel, an ad hoc questionnaire was administrated to 30 Country Agents (CAs) to gather measures routinely adopted at local level. To facilitate the comparison of measures, a three-level conceptual map was developed. RESULTS: The IDBs yielded at 207 measures that pertained mainly to non-health determinants of health, whereas the 352 measures obtained from CAs focused on process and outcome. A set of 33 common measures that related to immunization, morbidity and mortality were identified. CONCLUSIONS: A limited set of measures used both in IDBs and at national level identify common areas of concerns that certainly capture crucial issues with child prevention and health outcomes. However, they are far from satisfying a child-centric multi-dimensional approach to the evaluation of child well-being and well-becoming. There is room for improvement at both international and national levels. IDBs should include and harmonize measures that concern the provision of child-centric services and encompass physical, social and mental development. At the national level, efforts towards the inclusion of measures that concern non-health determinants of health should be pursued.

Effect of South Africa's interim mandatory salt reduction programme on urinary sodium excretion and blood pressure.

South Africa implemented legislation in June 2016 mandating maximum sodium (Na) levels in processed foods. A pre-post impact evaluation assessed whether the interim legislative approach reduced salt intake and blood pressure. Baseline Na intake was assessed in a nested cohort of the WHO Study on global AGEing and adult health (WHO-SAGE) Wave 2 (Aug-Dec 2015). 24-hour urine samples were collected in a random subsample (n = 1,299; of which n = 750 were considered valid (volume ≥ 300 mL and creatinine ≥ 4 mmol/day (women) or ≥ 6 mmol/day (men))). Follow-up urine samples were collected in Wave 3 (Jun 2018-Jun 2019), with replacements included for those lost to follow-up (n = 1,189; n = 548 valid). In those aged 18 - 49y, median salt intake was 7.8 (4.7, 12.0) g/day in W2 (n = 274), remaining similar in the W3 sample (7.7 (4.9, 11.3) g salt/day (n = 92); P = 0.569). In older adults (50 + y), median salt intake was 5.8 (4.0, 8.5) g/day (n = 467) in W2, and 6.0 (4.0, 8.6) g/day (n = 455) in W3 (P = 0.721). Controlling for differences in background characteristics, overall salt intake dropped by 1.15 g/day (P = 0.028). 24hr urinary Na concentrations from a countrywide South African sample suggest that salt intakes have dropped during the interim phase of mandatory sodium legislation. Further measurement of population level salt intake following stricter Na targets, enforced from June 2019, is necessary.

Quality of life improvement in children with attention-deficit hyperactivity disorder reduces family's strain: A structural equation model approach.

OBJECTIVES: The objective of the study is to analyse how the quality of life of children diagnosed with attention-deficit/hyperactivity disorder (ADHD) impacts the relationship between disease severity and family burden. METHOD: The data collected by a longitudinal, observational study involving 1478 children with ADHD residing in 10 European countries (aged 6 to 18 years) were analysed to evaluate the relationships between ADHD severity, the children's quality of life and family burden. RESULTS: The disorder's severity directly and indirectly affected the children's health-related quality of life (HRQoL) and family burden. The degree of family burden was modulated by the children's HRQoL. CONCLUSIONS: One of the primary causes of the stress experienced by parents of children with ADHD is their perception of the child's reduced HRQoL and not the symptom severity itself. Efforts to minimize symptom severity cannot alone reduce family burden.

Identifying co-occurrence and clustering of chronic diseases using latent class analysis: cross-sectional findings from SAGE South Africa Wave 2.

OBJECTIVES: To classify South African adults with chronic health conditions for multimorbidity (MM) risk, and to determine sociodemographic, anthropometric and behavioural factors associated with identified patterns of MM, using data from the WHO's Study on global AGEing and adult health South Africa Wave 2. DESIGN: Nationally representative (for ≥50-year-old adults) cross-sectional study. SETTING: Adults in South Africa between 2014 and 2015. PARTICIPANTS: 1967 individuals (men: 623 and women: 1344) aged ≥45 years for whom data on all seven health conditions and socioeconomic, demographic, behavioural, and anthropological information were available. MEASURES: MM latent classes. RESULTS: The prevalence of MM (coexistence of two or more non-communicable diseases (NCDs)) was 21%. The latent class analysis identified three groups namely: minimal MM risk (83%), concordant (hypertension and diabetes) MM (11%) and discordant (angina, asthma, chronic lung disease, arthritis and depression) MM (6%). Using the minimal MM risk group as the reference, female (relative risk ratio (RRR)=4.57; 95% CI (1.64 to 12.75); p =0.004) and older (RRR=1.08; 95% CI (1.04 to 1.12); p<0.001) participants were more likely to belong to the concordant MM group, while tobacco users (RRR=8.41; 95% CI (1.93 to 36.69); p=0.005) and older (RRR=1.09; 95% CI (1.03 to 1.15); p=0.002) participants had a high likelihood of belonging to the discordant MM group. CONCLUSION: NCDs with similar pathophysiological risk profiles tend to cluster together in older people. Risk factors for MM in South African adults include sex, age and tobacco use.

Determinants of change in blood pressure in Ghana: Longitudinal data from WHO-SAGE Waves 1-3.

The prevalence of hypertension is increasing in low- and middle-income countries, however statistics are generally derived from cross sectional surveys that utilize different methodologies and population samples. We investigated blood pressure (BP) changes over 11-12 years in a large cohort of adults aged 50 years and older (n = 820) included in the World Health Organization's Study on global AGEing and adult health (WHO-SAGE Ghana) Wave 1 (2007/8) with follow up in Wave 3 (2019). Participants' BP were measured in triplicate and a survey completed at both time points. Survey instruments collected information on sociodemographic characteristics, lifestyle, health behaviors and chronic conditions. While no significant difference was found in systolic BP between Waves 1 and 3, diastolic BP decreased by 9.7mmHg (mean = 88.6, 15.4 to 78.9, 13.6 respectively) and pulse pressure increased by 9.5mmHg (44.8, 13.7 to 54.3, 14.1). Awareness of hypertension increased by 37%, from (20% to 57%), but no differences were found for the proportion of hypertensives receiving treatment nor those that had controlled BP. Mixed effects modelling showed a decrease in diastolic BP was associated with increasing age, living in rural areas and having health insurance. Factors associated with an increased awareness of hypertension were residing in urban areas, having health insurance and increasing body mass index. While diagnosis of hypertension has improved over time in Ghana, there is an ongoing need to improve its treatment in older adults.

Variability in the assessment of children's primary healthcare in 30 European countries.

BACKGROUND: The high variability in the types and number of measures adopted to evaluate childcare across European countries makes it necessary to investigate country practices to identify trends in setting national priorities in the assessment of child well-being. OBJECTIVE: This paper intends to investigate country practices under the lens of variability to explore possible trends in setting national priority in the evaluation of childcare. In particular, it analyses variability considering to what extent this depends on the tendency of adopting a broad vision (i.e. selecting measures for a larger variety of aspects) or whether this is influenced by the choice of adopting an in-depth approach (i.e. using more measures to analyse a specific aspect). METHODS: An ad hoc questionnaire was administered to a national expert in each country and yielded 352 measures. To analyse variability, the breadth in the number of aspects considered was explored using a convergence index, while the depth in the distribution of measures in each aspect was investigated by computing a coefficient of variation. Countries were grouped by adopting a hierarchical clustering approach. RESULTS: There is a high variability across countries in the selection of measures that cover different aspects of childcare. Preferences in the distribution of measures are significant even at the domain level and in countries that use a limited number of measures and become more evident at the category and sub-category levels. The statistical analysis clusters countries in four main groups and two outliers. The in-depth distribution of measures focused on a specific aspect shows a homogeneous pattern, with the identification of two main groups of countries. CONCLUSIONS: A limited set of measures are shared across countries hampering a robust comparison of paediatric models. The selection of measures shows that the evaluation is closely related to national priorities as resulting from the number and types of measures adopted. Moreover, a range of a reasonable number of measures can be hypothesized to address the quality of childcare under a multi-dimensional perspective.

Salt-reduction strategies may compromise salt iodization programs: Learnings from South Africa and Ghana.

OBJECTIVES: Universal salt iodization has been adopted by many countries to address iodine deficiency. More recently, salt-reduction strategies have been widely implemented to meet global salt intake targets of <5 g/d. Compatibility of the two policies has yet to be demonstrated. This study compares urinary iodine excretion (UIE) according to 24-h urinary sodium excretion, between South Africa (SA) and Ghana; both countries have implemented universal salt iodization, but in Ghana no salt-reduction legislation has been implemented. METHODS: Participants from the World Health Organization's Study on Global Ageing and Adult Health Wave 3, with survey and valid 24-h urinary data (Ghana, n = 495; SA, n = 707), comprised the sample. Median 24-h UIE was compared across salt intake categories of <5, 5-9 and >9 g/d. RESULTS: In Ghana, median sodium excretion indicated a salt intake of 10.7 g/d (interquartile range [IQR] = 7.6), and median UIE was 182.4 µg/L (IQR = 162.5). In SA, both values were lower: median salt = 5.6 g/d (IQR = 5.0), median UIE = 100.2 µg/L (IQR = 129.6). UIE differed significantly across salt intake categories (P < 0.001) in both countries, with positive correlations observed in both-Ghana: r = 0.1501, P < 0.0011; South Africa: r = 0.4050, P < 0.0001. Participants with salt intakes <9 g/d in SA did not meet the World Health Organization's recommended iodine intake of 150 µg/d, but this was not the case in Ghana. CONCLUSIONS: Monitoring and surveillance of iodine status is recommended in countries that have introduced salt-reduction strategies, in order to prevent reemergence of iodine deficiency.

[The result of application's monitoring of NEWS score in a surgery unit of a North Italy hospital]. / Risultati del monitoraggio dell'applicazione dello score National Early Warning Score in area chirurgica di un ospedale del Nord Italia.

INTRODUCTION: In a hospital in Northern Italy was decided to experiment a new standardized methodology for detection and evaluation of vital parameters and effective communication between healthcare professionals, with the applications of NEWS score. Then it was necessary to evaluate the application and usefulness of the score in the specific contest. The aim of this project was adopting a validated and standardized methodology for detecting vital parameters to identificate early the signs and symptoms of a possible clinical deterioration and to create an effective communication between professionals. In the end it was necessary to monitor the correct application of the NEWS score to evaluate the usefulness of extending the score in surgical units. METHODS: The indicators were identified and monitored, consulting a sample of medical Gynecologic records of the 2019. The sample size useful for having a confidence level of 95% was identified, which, according to the Sample Size Calculator, known the population of 865 patients, corresponds to 160 sample units. An ad hoc data set was then developed for data collection. RESULTS: The correctness of the execution of clinical monitoring according to the parameters provided by the score is 75%, while the completeness of score's recording is 99% of the sample analyzed. The days of hospitalization in which there is a score≥5 are 10, equal to 1.5%. An in-depth study of cases with a score ≥5 showed that in 9 out of 10 cases the doctor was alerted. DISCUSSION: The NEWS score is useful in the early identification of risk situations, in rapid and objective communication and in the timely activation of interventions to prevent complications. Furthermore, the application of the score does not involve a waste of time than that used for the collection of vital parameters.

Salt and potassium intake among adult Ghanaians: WHO-SAGE Ghana Wave 3.

Though Ghana has high hypertension prevalence, the country lacks current national salt consumption data required to build and enhance advocacy for salt reduction. We explored the characteristics of a randomly selected sub sample that had valid urine collection, along with matched survey, anthropometric and BP data (n = 839, mean age = 60y), from the World Health Organization's Study on global AGEing and adult health (WHO-SAGE), Ghana Wave 3, n = 3053). We also investigated the relationship between salt intake and blood pressure (BP) among the cohort. BP was measured in triplicate and 24 h urine was collected for the determination of urinary sodium (Na), potassium (K), creatinine (Cr) and iodine levels. Hypertension prevalence was 44.3%. Median salt intake was 8.3 g/day, higher in women compared to men (8.6, interquartile range (IQR) 7.5 g/day vs 7.5, IQR 7.4 g/day, p <  0.01), younger participants (18-49 y) compared to older ones (50+ y) (9.7, IQR 7.9 g/day vs 8.1, IQR 7.1 g/day, p <  0.01) and those with higher Body Mass Index (BMI) (> 30 kg/m2) compared to a healthy BMI (18.5-24.9 kg/m2) (10.04, IQR 5.1 g/day vs 6.2, IQR 5.6 g/day, p <  0.01). More than three quarters (77%, n = 647) of participants had salt intakes above the WHO maximum recommendation of 5 g/d, and nearly two thirds (65%, n = 548) had daily K intakes below the recommended level of 90 mmol. Dietary sodium to potassium (Na: K) ratios above 2 mmol/mmol were positively associated with increasing BP with age. Population-based interventions to reduce salt intake and increase K consumption are needed.

Predicting steady-state endoxifen plasma concentrations in breast cancer patients by CYP2D6 genotyping or phenotyping. Which approach is more reliable?

In previous studies, steady-state Z-endoxifen plasma concentrations (ENDOss) correlated with relapse-free survival in women on tamoxifen (TAM) treatment for breast cancer. ENDOss also correlated significantly with CYP2D6 genotype (activity score) and CYP2D6 phenotype (dextromethorphan test). Our aim was to ascertain which method for assessing CYP2D6 activity is more reliable in predicting ENDOss. The study concerned 203 Caucasian women on tamoxifen-adjuvant therapy (20 mg q.d.). Before starting treatment, CYP2D6 was genotyped (and activity scores computed), and the urinary log(dextromethorphan/dextrorphan) ratio [log(DM/DX)] was calculated after 15 mg of oral dextromethorphan. Plasma concentrations of TAM, N-desmethyl-tamoxifen (ND-TAM), Z-4OH-tamoxifen (4OH-TAM) and ENDO were assayed 1, 4, and 8 months after first administering TAM. Multivariable regression analysis was used to identify the clinical and laboratory variables predicting log-transformed ENDOss (log-ENDOss). Genotype-derived CYP2D6 phenotypes (PM, IM, NM, EM) and log(DM/DX) correlated independently with log-ENDOss. Genotype-phenotype concordance was almost complete only for poor metabolizers, whereas it emerged that 34% of intermediate, normal, and ultrarapid metabolizers were classified differently based on log(DM/DX). Multivariable regression analysis selected log(DM/DX) as the best predictor, with patients' age, weak inhibitor use, and CYP2D6 phenotype decreasingly important: log-ENDOss = 0.162 - log(DM/DX) × 0.170 + age × 0.0063 - weak inhibitor use × 0.250 + IM × 0.105 + (NM + UM) × 0.210; (R2  = 0.51). In conclusion, log(DM/DX) seems superior to genotype-derived CYP2D6 phenotype in predicting ENDOss.