Occult hepatitis B infection in children born to HBeAg-positive women confers a low long-term risk for HBsAg-positive infection.

PURPOSE: Mother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI. METHODS: One-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018. RESULTS: Six children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1 year. One of them was transiently HBsAg-positive at the age of 7 years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections. CONCLUSION: The results indicate that children born to mothers with high HBV DNA levels have approximately 10% risk to develop OBI despite antiviral treatment, vaccination and HBIG, but that such OBI confers a minimal long-term risk for overt infection, at least in immunocompetent children.

Hepatitis B virus particles in serum contain minus strand DNA and degraded pregenomic RNA of variable and inverse lengths.

This study utilized digital PCR to quantify HBV RNA and HBV DNA within three regions of the HBV genome. Analysis of 75 serum samples from patients with chronic infection showed that HBV RNA levels were higher in core than in S and X regions (median 7.20 vs. 6.80 and 6.58 log copies/mL; p < .0001), whereas HBV DNA levels showed an inverse gradient (7.71 vs. 7.73 and 7.77 log copies/mL, p < .001). On average 80% of the nucleic acid was DNA by quantification in core. The core DNA/RNA ratio was associated with viral load and genotype. In individual patients, the relations between RNA levels in core, S and X were stable over time (n = 29; p = .006). The results suggest that pregenomic RNA is completely reverse transcribed to minus DNA in ≈75% of the virus particles, whereas the remaining 25% contain both RNA and DNA of lengths that reflect variable progress of the polymerase.

Toxicity Screening of Fungal Extracts and Metabolites, Xenobiotic Chemicals, and Indoor Dusts with In Vitro and Ex Vivo Bioassay Methods.

It is controversial how useful bioassays are for identifying the in vivo toxicity of hazardous environmental exposures. In this study, fruiting bodies of forest mushrooms (n = 46), indoor mold colonies (n = 412), fungal secondary metabolites (n = 18), xenobiotic chemicals such as biocides and detergents (n = 6), and methanol extracts of indoor dusts from urban buildings (n = 26) were screened with two different bioactivity assays: boar sperm motility inhibition (BSMI) and inhibition of cell proliferation (ICP) tests. For the forest mushrooms, the toxicity testing result was positive for 100% of poisonous-classified species, 69% of non-edible-classified species, and 18% of edible-classified species. Colonies of 21 isolates of Ascomycota mold fungal species previously isolated from water-damaged buildings proved to be toxic in the tests. Out of the fungal metabolites and xenobiotic chemicals, 94% and 100% were toxic, respectively. Out of the indoor dusts from moldy-classified houses (n = 12) and from dry, mold-free houses (n = 14), 50% and 57% were toxic, respectively. The bioassay tests, however, could not differentiate the samples from indoor dusts of moldy-classified buildings from those from the mold-free buildings. Xenobiotic chemicals and indoor dusts were more toxic in the BSMI assay than in the ICP assay, whereas the opposite results were obtained with the Ascomycota mold colonies and fungal secondary metabolites. The tests recognized unknown methanol-soluble thermoresistant substances in indoor settled dusts. Toxic indoor dusts may indicate a harmful exposure, regardless of whether the toxicity is due to xenobiotic chemicals or microbial metabolites.

Chronic widespread pain and cause of death: a 25-year follow-up study.

Introduction: Chronic widespread pain (CWP) has been suggested as a risk factor for mortality in cardiovascular diseases and malignancies. Different definition of CWP makes it difficult to compare previous studies. Objectives: The aim was to study whether mortality and certain causes of death were increased among people with CWP and whether the definition of CWP influenced outcome. Methods: This 25-year follow-up study included 2425 people from the general population, at baseline divided into 3 pain groups: CWP, chronic regional pain, and no chronic pain (NCP). Chronic widespread pain was defined according to the ACR1990 (CWPACR1990) and the more stringent WP2019 (CWPWP2019) criteria. Causes of death were derived from official national register. Mortality, adjusted for age, sex, socioeconomic status, and smoking habits were analyzed with Cox regression. Results: Overall mortality was not higher in people with CWPACR1990 (hazard ratio [HR] 1.08, P = 0.484) compared with NCP but significantly higher when using CWPWP2019 (HR 1.32, P = 0.033). People with CWPWP2019 had a higher mortality in diseases of the circulatory system (HR 1.32, P = 0.033) but not for neoplastic diseases. CWPACR1990 showed an increased mortality in malignancies of digestive organs. An increased mortality in influenza, pneumonia, acute kidney failure, and chronic kidney disease was observed for the CWPWP2019 definition. Conclusion: The more stringent WP2019 definition of CWP showed an excess risk for death, especially within diseases of the circulatory system. The results suggest that WP2019 defines a more vulnerable group in the population. Chronic widespread pain should be acknowledged in the clinic as a risk factor for increased mortality.

Development of radiographic knee osteoarthritis and the associations to radiographic changes and baseline variables in individuals with knee pain: a 2-year longitudinal study.

OBJECTIVES: The aim was to study the development of radiographic knee osteoarthritis (RKOA) in individuals with knee pain over 2 years, and the associations between radiographic changes and baseline variables. DESIGN: Longitudinal cohort study. PARTICIPANTS AND SETTING: This study is part of the Halland Osteoarthritis cohort. The included 178 individuals, aged 30-67, had knee pain, without cruciate ligament injury or radiographic findings and 67% were women. The presence of RKOA was defined as Ahlbäck score of ≥1 in ≥1 knee. (Ahlbäck grade 1: joint space narrowing in the tibiofemoral joint <3 mm). Diagnosis of clinical KOA was based on the clinical guideline from the National Institute for Health and Care Excellence (NICE). Knee injury and Osteoarthritis Outcome Score (KOOS), pain intensity, physical function, body mass index (BMI) and visceral fat area (VFA) were measured. Associations to RKOA were analysed with logistic regression (OR). RESULTS: In all, 13.8% (n=24) developed RKOA in 2 years whereof all had clinical KOA at baseline, as defined by NICE. Deterioration to RKOA was significantly associated with higher BMI, OR 1.119 (95% CI 1.024 to 1.223; p=0.013), and VFA, 1.008 (95% CI 1.000 to 1.016; p=0.049), worse knee pain intensity, 1.238 (95% CI 1.028 to 1.490; p=0.024), worse scores for KOOS Pain, 0.964 (95% CI 0.937 to 0.992; p=0.013) and KOOS Symptoms, 0.967 (95% CI 0.939 to 0.996; p=0.027), KOOS Activities of daily living 0.965 (95% CI 0.935 to 0.996; p=0.026) and KOOS Quality of Life 0.973 (95% CI 0.947 to 0.999; p=0.044), at baseline. CONCLUSIONS: One out of seven individuals with clinical KOA developed RKOA in only 2 years. Baseline variables associated with RKOA after 2 years may possibly be detected early by using the NICE guideline, assessment of obesity and self-reported data of symptoms to support first-line treatment: education, exercise and weight control. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04928170).

Co-occurrence of bacteria and viruses and serotype distribution of Streptococcus pneumoniae in the nasopharynx of Tanzanian children below 2 years of age following introduction of the PCV13.

Introduction: Pneumococcal conjugate vaccines have reduced severe disease attributed to vaccine-type pneumococci in children. However, the effect is dependent on serotype distribution in the population and disease development may be influenced by co-occurrence of viral and bacterial pathogens in the nasopharynx. Methods: Following introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Tanzania we performed repeated cross-sectional surveys, including 775 children below 2 years of age attending primary healthcare centers. All children were sampled from nasopharynx and pneumococci were detected by single-target PCR. Pneumococcal serotypes/groups and presence of viruses and other bacteria were determined by two multiplex PCR assays. Results: The prevalence of PCV13 vaccine-type pneumococci decreased by 50%, but residual vaccine-types were still detected in 21% of the children 2 years after PCV13 introduction. An increase in the non-vaccine-type 15 BC was observed. Pneumococci were often co-occurring with Haemophilus influenzae, and detection of rhino/enterovirus was associated with higher pneumococcal load. Discussion: We conclude that presence of residual vaccine-type and emerging non-vaccine-type pneumococci in Tanzanian children demand continued pneumococcal surveillance. High co-occurrence of viral and bacterial pathogens may contribute to the disease burden and indicate the need of multiple public health interventions to improve child health in Tanzania.

Enrichment reveals extensive integration of hepatitis B virus DNA in hepatitis delta-infected patients.

INTRODUCTION: Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited. METHODS: We investigated 50 pieces of liver explant tissue from five patients with hepatitis D-induced cirrhosis, using a deep sequencing strategy targeting HBV RNA. RESULTS: We found that integrations were abundant and highly expressed, however with large variation in number of integration derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of both HBsAg. Still, most of the HBV reads represented a few predominant integrations. CONCLUSIONS: The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small part of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV co-infected patients with liver cirrhosis.

Close relatives' perspective of critical illness due to COVID-19: Keeping in touch at a distance.

AIM: To elucidate the meaning of being a close relative of a critically ill person cared for in intensive care during the initial phase of the COVID-19 pandemic. DESIGN: A narrative inquiry design following the COREQ guidelines. METHODS: Individual interviews with fifteen close relatives of patients critically ill with COVID-19 were analysed using phenomenological hermeneutics. RESULTS: The surreal existence of not being allowed to be near was emotionally difficult. While distancing due to restrictions was challenging, physicians' phone calls served as a connection to their relatives and brought a sense of security. Keeping notes helped them remember what happened and brought order to a chaotic situation. CONCLUSION: Close relatives feel secure when they receive regular information about their critically ill relative, not just when their condition worsens. They wish to be physically near to their critically ill person; when this is impossible, digital technology can provide support, but further accessibility developments are needed.

Iodine intake in the Swiss population 100 years after the introduction of iodised salt: a cross-sectional national study in children and pregnant women.

PURPOSE: The Swiss voluntary salt iodisation programme has successfully prevented iodine deficiency for 100 years, but dietary habits are changing and today only one-third of processed foods contain iodised salt. We aimed to monitor the current iodine status in children and pregnant women. METHODS: We conducted a nationwide cross-sectional study in children (6-12 years) and pregnant women and measured the urinary iodine concentration (UIC) in spot urine samples. We estimated the iodine intake using UIC and urinary creatinine concentration (UCC) and determined the prevalence of intakes below the average requirement (AR) using the SPADE method. We measured dried blood spot (DBS) thyroglobulin (Tg), TSH and total T4 in pregnant women. RESULTS: The median UIC was 127 µg/L (bootstrapped 95% CI 119, 140, n = 362) in children and 97 µg/L (bootstrapped 95% CI 90, 106, n = 473) in pregnant women. The estimated prevalence of inadequate iodine intake (< 65 µg/day) was 5.4% (bootstrapped 95% CI 0.0, 14.6) in children. Half (47%) of the women consumed iodine-containing multivitamin and mineral supplements (≥ 150 µg/day). Compared to non-users, users had higher median UIC (129 vs. 81 µg/L, P < 0.001), lower prevalence of inadequacy (< 160 µg/day; 0.2 vs. 31%) and lower DBS-Tg (23 vs. 29 µg/L, P < 0.001). All women were euthyroid. CONCLUSIONS: The Swiss diet and current salt fortification provides adequate iodine intake in children, but not in all pregnant women. Iodine supplements cover the dietary gap in pregnancy but are not universally consumed. Therefore, improved use of iodised salt in processed foods is desired to ensure adequate iodine intake in all population groups. This trial was registered at clinicaltrials.gov as NCT04524013.

Detection of drugs and hepatitis C virus in used syringes from a needle exchange in Gothenburg, Sweden.

People who inject drugs (PWID) are exposed to serious health risks such as lethal overdoses, addiction and infections. The patterns of drug use and the prevalence of hepatitis C virus (HCV) infection vary greatly between and even within countries. Data on drugs used for injection are important to inform PWID of risks and adapt healthcare. This study aimed to determine which substances are injected in Gothenburg, Sweden, and estimate the risk of HCV transmission. A total of 150 syringes handed in at the needle and syringe exchange program (NEP) in Gothenburg over a week in November 2021 were analysed for drug content using liquid chromatography coupled with high-resolution mass spectrometry. Using a dose-adjusted comparison, the main drug(s) injected was distinguished from the impurities in the syringes containing several drugs. HCV RNA was quantified by real-time PCR in an additional set of 150 syringes. Drugs were detected in >99% of analysed syringes, and the most common drugs were amphetamine (81%), followed by buprenorphine (8.0%), heroin (6.7%) and alprazolam (4.6%). Less common findings were testosterone (2.7%), methylphenidate (2.0%), MDMA (0.7%), trenbolone (0.7%) and zopiclone (0.7%). Eleven syringes (7.3%) contained more than one drug. HCV RNA was detected in 13% of the syringes, and one in 10 contained enough to potentially transmit an infection. This study underlines the importance of access to NEPs for PWID to reduce the risks associated with drug injection.

Complex norovirus transmission dynamics at hospital wards revealed by deep sequencing.

Detailed knowledge regarding norovirus transmission within hospitals is limited. We investigated a norovirus hospital outbreak affecting 65 patients at five different wards. PCR showed that 61 (94%) of the patients were infected with genotype II.4 strains. Successful Ion Torrent deep sequencing of GII.4 positive samples from 59 patients followed by phylogenetic analysis revealed that all sequences but two clustered into four distinct clades. Two of the clades belonged to GII.4 Sydney 2012, while the other two belonged to GII.4 New Orleans 2009. One of the clades was predominant at two wards, while two clades were predominant at one ward each. The fourth clade was found in sporadic cases at several wards. Thus, at four out of five wards, variants from one clade were predominant. At one ward, a single clade accounted for all cases, while at three wards the predominant clade accounted for 60%-71% of cases. Analysis of quasispecies variation identified positions that could further discriminate between variants from separate wards. The results illustrate a complex transmission of healthcare-associated norovirus infections and show that sequencing can be used to discriminate between related and unrelated cases.

National monitoring of iodine, sodium, and vitamin D status in toddlers and women of childbearing age - results and lessons learned from a pilot study in Norway.

Background: Norway is lacking a population-based national monitoring program for iodine, sodium, and vitamin D status. Objective: The aim of this study was to pilot-test a study design for collecting biological samples from a country-representative sample of 2-year-old children and their mothers and to report results for iodine, salt, and vitamin D at baseline, before initiation of salt iodization in Norway. Design: In a cross-sectional study, we recruited 2-year-old children and their mothers during the routine 2-year check-up through 38 randomly selected health clinics in 2021. Spot urine samples were analyzed for iodine, creatinine, and sodium, and dried blood spots from the mothers were analyzed for thyroglobulin (Tg) and 25-hydroxyvitamin D (25(OH)D). Results: We aimed at including 400 mother-child pairs but recruited only 55 pairs. Major challenges were closed health clinics due to the COVID-19 pandemic, lack of motivation of the health personnel to prioritize recruiting, missing information about non-participation, and high workload for participants. The median urinary iodine concentration (UIC) was 123 (95% CI: 76, 228) µg/L in the toddlers and 83 (95% CI: 72, 99) µg/L in the mothers. The median urinary sodium concentration (UNaC) was 62 (95% CI: 37, 91) mmol/L in the toddlers and 93 (95% CI: 77, 107) mmol/L in the mothers. Of the mothers, 18% had levels of 25(OH)D <50 nmol/L (suboptimal status). Discussion and conclusion: Lessons learned from the pilot study will be used to design a national monitoring program for toddlers and women of childbearing age in Norway. The results indicate that 2-year-old children and women of childbearing age in Norway may have inadequate iodine intakes at the group level, while for vitamin D, most of the mothers had adequate status.

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia.

Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination. Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides. Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors. Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.

Incidence of cardiovascular and bleeding events and reasons for discontinuation in patients with chronic lymphocytic leukemia treated with ibrutinib-A retrospective analysis on consecutive patients from a well-defined region.

OBJECTIVE: Ibrutinib treatment is associated with cardiovascular side effects, in particular atrial fibrillation (AF) and hypertension, as well as increased risk of bleeding. Here, we aimed at describing the incidence of these events during long-term follow-up in patients with chronic lymphocytic leukemia treated outside clinical trials as well as identifying clinical factors predictive of developing AF. Additionally, other reasons for treatment withdrawal were analyzed. METHODS: The study was retrospective, data were collected from medical records. RESULTS: A total of 134 patients were identified. Median follow-up was 32 months (range 3-103) and median duration of ibrutinib treatment was 26 months (range 1-103). Of 110 patients with no prior history of AF, 24.5% were diagnosed during treatment. Newly diagnosed or worsening of pre-existing hypertension occurred in 15.7%. Sixty-six % of the patients experienced bleeding events, of which 7.5% grade 3-4. Treatment discontinuation and dose reduction occurred in 68% and 47% of the patients, respectively, mostly due to toxicity. CONCLUSIONS: The incidence of AF was high and at a median follow-up of 2.5 years, two-thirds of the patients discontinued treatment mostly due to bleeding and infections. Treatment-related toxicity of any grade should be regarded as a concern of prolonged ibrutinib therapy.

Thyroid function and urinary concentrations of iodine, selenium, and arsenic in vegans, lacto-ovo vegetarians and pescatarians.

PURPOSE: Populations following a plant-based diet may be at particular risk of thyroid dysfunction due to low iodine and selenium intakes. The main purpose was to assess thyroid function and urinary concentration of iodine, selenium, and arsenic, in subjects following a vegan, lacto-ovo vegetarian, or pescatarian diet. METHODS: In Norway, a country without mandatory dietary iodine fortification, 205 adults, following vegan (n = 115), lacto-ovo vegetarian (n = 55) and pescatarian diet (n = 35) were included. Thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and serum anti-TPO (S-anti-TPO) were measured in a venous blood sample and concentrations of iodine (UIC), creatinine (UCC), selenium, and arsenic were measured from single spot urine samples. RESULTS: Subclinical hypothyroidism (TSH > 4.0 mU/L) was observed in 3% of subjects. The overall median (p25, p75) Tg was 17 (9, 30) µg/L and vegans had higher Tg compared to pescatarians. Vegans not consuming iodine-containing supplements (n = 43) had higher Tg, than supplement users (n = 72), 27 (11, 44) vs. 16 (8, 25) µg/L and higher fT4, 16 (15, 17) vs. 15 (14, 17) pmol/L, respectively. The overall median UIC was 57 (28, 130) µg/L, all dietary groups had median UIC below WHO thresholds. Median urinary selenium and arsenic concentration was 13 (6, 22) and 3 (2, 8) µg/L, respectively. CONCLUSION: The prevalence of subclinical hypothyroidism was low and fT4 and fT3 were within the normal range for all dietary groups. Vegans had significantly increased Tg compared to pescatarians.

Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain.

OBJECTIVE: The aim was to study associations between chronic widespread pain, widespread pain sensitivity, leptin, and metabolic factors in individuals with knee pain. A secondary aim was to study these associations in a subgroup of individuals with normal BMI. METHOD: This cross-sectional study included 265 individuals. The participants were categorised into three different pain groups: Chronic widespread pain (CWP), chronic regional pain (ChRP), or no chronic pain (NCP). The pressure pain thresholds (PPTs) were assessed using computerised pressure algometry. Low PPTs were defined as having PPTs in the lowest third of all tender points. Leptin and metabolic factors such as BMI, visceral fat area (VFA), lipids, and glucose were also assessed. RESULT: Sixteen per cent reported CWP, 15% had low PPTs, and 4% fulfilled both criteria. Those who fulfilled the criteria for CWP were more often women, more obese, and had increased leptin levels. In logistic regression, adjusted for age and gender, leptin was associated with fulfilling criteria for CWP, OR 1.015 (95% CI 1.004-1.027, p = 0.008). In logistic regression, adjusted for age and gender, leptin was associated with low PPTs, OR 1.016 (95% CI 1.004-1.029, p = 0.012). Leptin was also associated with fulfilling both criteria, adjusted for age, sex, and visceral fat area (VFA), OR 1.030 (95% CI 1.001-1.060), p = 0.040. CONCLUSION: Leptin was associated with fulfilling the combined criteria for chronic widespread pain and low PPTs, even after adjusting for the visceral fat area (VFA). Longitudinal studies are needed to study the causal relationships between leptin and the development of widespread pain. TRIAL REGISTRATION: clinicalTrials.gov Identifier: NCT04928170.

Health literacy in individuals with knee pain-a mixed methods study.

BACKGROUND: Low health literacy is associated with worse pain and poorer self-management. This study (1) examined the level of health literacy and associations with lifestyle habits, health status, chronic pain, and radiographic knee osteoarthritis; and (2) explored experiences illuminating health literacy among individuals with knee pain. METHODS: A convergent parallel mixed-methods design was used, including 221 individuals. Health literacy was assessed by HLS-EU-Q16 and eHEALS. The questionnaire included questions on lifestyle habits, health status, and pain distribution. Radiographic knee osteoarthritis was assessed with x-rays. Associations were analysed using logistic regression analyses. Individual semi-structured interviews were conducted (n = 19) and analysed with qualitative content analysis. RESULTS: The result showed that 71% reported sufficient health literacy. Higher education, healthy lifestyle habits, better general health, and absence of widespread pain were associated with sufficient health literacy. Experiences regarding health literacy influencing the decision-making process toward a decision on action comprised: (1) searching for information actively or passively; (2) processing of the information included being informed, critical, and interpretive; and (3) taking a stand on the information based on trustfulness and motivation. CONCLUSION: Seven out of 10 reported sufficient health literacy. Despite this, unhealthy lifestyles were common, suggesting that having sufficient HL is not enough for a behavioural change and the decision-making process, including different phases such as searching, processing, and taking a stand on health information is important to consider. More research on health literacy is needed to gain knowledge of how best to develop health promotion in individuals with knee pain.

Long-term fracture risk in rheumatoid arthritis: impact of early sustained DAS28-remission and restored function, progressive erosive disease, body mass index, autoantibody positivity and glucocorticoids. A cohort study over 10 years.

BACKGROUND: Risk of fragility fractures in patients with rheumatoid arthritis (RA) is increased. Disease-related inflammation in RA is associated with low Bone Mineral Density (BMD). However, effects of specific disease factors on fracture occurrence and whether or not such disease effects are independent of BMD are unknown. METHODS: Analysis of fracture outcome in the prospective cohort of 2557 patients with early RA (67% women, mean age 58.1 ± 15.6 years) during an observation period of 10.6 ± 4.7 years. In 602 patients BMD was measured at baseline. The first major fragility fractures were considered. Kaplan-Meier and Cox regression analysis, adjusted for traditional factors, prior fracture, disease activity and period of inclusion, were used to estimate the risk of the outcome. RESULTS: During follow-up fracture occurred in 352 patients (13.8%), a rate of 13/1000 p-y. A proportional risk reduction for the outcome was associated with Body Mass Index (BMI) at baseline, BMI ≥ 30 kg/m2, and over the first two years sustained Disease Activity Score (DAS28)-remission, DAS28-low disease activity and Health Assessment Questionnaire (HAQ) ≤ 0.5. The proportional risk elevation for fractures was associated with BMI ≤ 20 kg/m2, DAS28 at baseline, 6-month and at 1-year, cumulative DAS28 over the two years, RF, erosion score progression at 2-year, HAQ score and HAQ ≥ 1 at 6-month and 1-year and showed a trend for ACPA positivity. The estimated fracture risk was increased in users of glucocorticoids (GC), associated with a higher GC-dosage at follow-ups and a higher cumulative dosage over two years, independently of disease activity. With adjustment for BMD, there was no difference in fracture outcome by exposure to GC. The effects of a higher BMI, DAS28-remission and low HAQ ≤ 0.5 attained at 6-month of treatment initiation and sustained up to 2 years, RF, ACPA, and erosion score progression at 2-year were independent of low BMD. CONCLUSIONS: This analysis supports importance of RA-specific risk factors in early RA for future major fragility fractures. Treat-to-target strategy and restored functional capacity in early RA-disease are important to prevent fractures. Autoantibody positivity, progressively erosive disease, and low weight could have additional value for personalized fracture preventive strategies in early RA.

Estimating habitual iodine intake and prevalence of inadequacy from spot urine in cross-sectional studies: a modeling analysis to determine the required sample size.

BACKGROUND: The habitual/usual iodine intake and the prevalence of iodine inadequacy may be estimated from spot urinary iodine concentrations in cross-sectional studies by collecting a repeat spot urine in a subgroup of the study population and accounting for within-person variability in iodine intake. However, guidance on the required overall sample size (N) and the replicate rate (n) is lacking. OBJECTIVES: To determine the sample size (N) and replicate rate (n) needed to estimate the prevalence of iodine inadequacy in cross-sectional studies. METHODS: We used data from local observational studies conducted in women 17-49 y old in Switzerland (N = 308), South Africa (N = 154), and Tanzania (N = 190). All participants collected 2 spot urine samples. We calculated the iodine intake using urinary iodine concentrations and accounted for urine volume using urinary creatinine concentration. For each study population, we estimated the habitual iodine intake distribution and determined the prevalence of iodine intake below the average requirement using the Statistical Program to Assess habitual Dietary Exposure (SPADE). We used the obtained model parameters in power analyzes and estimated the prevalence of iodine inadequacy for different sample sizes (N = 400, 600, and 900) and replicate rates (n = 50, 100, 200, 400, 600, and 900). RESULTS: The estimated prevalence (95% CI) of inadequate iodine intake was 21% (15, 28%), 5.1% (1.3, 8.7%), and 8.2% (3.4, 13%) for Swiss, South African, and Tanzanian women, respectively. An N of 400 women, with a repeated measure (n) in 100 women, achieved a satisfactory precision of the prevalence estimate in all study populations. Increasing the replicate rate (n) improved the precision more effectively than increasing the N of the study. CONCLUSIONS: The sample size for cross-sectional studies aiming to assess the prevalence of inadequate iodine intake depend on the expected prevalence, the overall variance in intake, and the study design. However, an N of 400 participants with a repeated measure of 25% may be used as guidance when planning observational studies applying simple random sampling. This trial was registered at clinicaltrials.gov as NCT03731312.