Factors affecting self-perceived mental health in the general older population during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Mental health problems among older people are large public health concerns but often go unrecognized and undertreated. During COVID - 19 several restrictions regarding social contacts were launched, primarily for the old. The objective of this study is to investigate which factors that had the main negative affect on mental health in the older population during the pandemic. METHOD: A cross-sectional cohort study set in Swedish primary care during the pandemic years 2021-2022. The population constitutes of 70-80-years-old, N = 260. Instruments used are Geriatric depression scale 20 (GDS20); Hospital anxiety and depression scale (HADS), and Perceived stress scale 10 (PSS10). Sociodemography and risk factors are explored. Outcome measures are factors independently associated with decreased mental health. Analyses were performed for the group as a whole and with logistic regression models comparing individuals who stated they were mentally affected by the pandemic to individuals who stated they were not. RESULTS: Participants who stated they were mentally affected by the COVID - 19 pandemic reported significantly higher levels of anxiety (p < 0.001), depression (p < 0.001), and stress (p = 0.026) compared to those who stated they were not mentally affected. Explanatory regression models of up to 50% showed that following factors were prominent among individuals who reported a decline in their mental health due to the COVID - 19 pandemic (n = 24); impaired social life (OR 20.29, p < 0.001, CI 4.53-90.81), change in physical activity (OR 5.28, p = 0.01, CI 1.49-18.72), perceived family situation (OR 31.90, p = 0,007, CI 2,53-402.42), mild/moderate and high anxiety (OR 4.94, p = 0.034, CI 1.13-21.60, OR 7.96, p = 0.035, CI 1.16-54.53 respectively), and female gender (OR 6.52, p = 0.029, CI 1.22-34.92). CONCLUSION: Anxiety, family situation, social life and change in physical activity were the main factors influencing the 70-80-years-old's self-perceived mental health during the COVID - 19 pandemic. Long-term effects of social restrictions on mental health in the older population need to be further investigated.

COVID-19 Recovery: Consistent Absence of Cerebrospinal Fluid Biomarker Abnormalities in Patients With Neurocognitive Post-COVID Complications.

BACKGROUND: To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS: Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed. RESULTS: SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, ß2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies. CONCLUSIONS: We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.

Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis.

Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A. A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI). Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis). In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.

Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study.

In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14 days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.

Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage.

BACKGROUND: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. METHODS: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. RESULTS: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). CONCLUSIONS: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.

Exploring the association of parity and its interaction with history of preterm delivery on gestational duration.

PURPOSE: Preterm delivery is a major cause of child mortality. While the relationship between parity and preterm delivery is known, its association with gestational duration and variability remains underexplored. Differences in variance may suggest interaction with other well-established risk factors. METHODS: With 1.1 million spontaneous deliveries (1990-2012) from the Swedish Medical Birth Register, we assessed while accounting for potential confounders the effects of parity on the mean and variance of gestational duration, and its possible interactions with history of preterm delivery. Pedigrees allowed to account for nonobserved, shared confounders using linear mixed models. RESULTS: Parity has a modest association with mean gestational duration, but a large effect on its variance. For example, the first pregnancy had the shortest mean gestational duration, 0.29 days shorter (95% CI: -0.33, -0.25) than the second, and the largest variance (σ2 = 135 days2). Accounting for shared unobserved confounders highlighted a group effect bias, likely linked to the mothers' total number of offspring. Parity interacts with other risk factors, including previous preterm delivery where the magnitude of its effect increases with parity (up to 4.6 days effect difference). CONCLUSIONS: Nonshared factors across a mother's pregnancies highlight parity's importance to gain insight into the mechanisms governing the timing of delivery.

Significance and Interrelationship of the Symptoms Listed in the DSM Criteria for Premenstrual Dysphoric Disorder.

Objective: While premenstrual dysphoric disorder (PMDD) as defined in DSM has become an established diagnosis, and a formal indication for drug treatment, the relative impact of the disparate symptoms named in the criteria, and to what extent they indeed constitute parts of one syndrome, remains insufficiently clarified. We have therefore explored the frequency, impact, and inter-relationship of different PMDD symptoms. Method: Using a web survey, 10,457 Swedish women of fertile age were asked to retrospectively assess if they experience reduced functioning due to symptoms clearly associated with the premenstrual phase. Those responding affirmatively reported presence, severity, and impact of each symptom named in the PMDD criteria. Result: Nine percent reported impairing premenstrual symptoms. Whereas irritability was reported to cause impairment in 77% of those passing the gate questions, somatic symptoms were common but seldom causing impairment. A vast majority reported presence of at least 5 different symptoms, as required to meet the PMDD criteria, but few reported each of 5 different symptoms to be severe or impairing. An analysis of the association between symptoms revealed clear-cut clustering of somatic and mood symptoms, respectively. Conclusion: While retrospective account suggested irritability to be the clinically most important premenstrual symptom, some of the complaints named in the PMDD criteria were not or only weakly associated with mood symptoms and also reported to be of limited clinical significance. It is concluded that regarding all symptoms listed in the DSM criteria as clinically relevant manifestations of one and the same syndrome may be questioned.

The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis.

Introduction: Myeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in CALR and MPL are also frequent. Mutations seen in additional genes are also often the same regardless of subtype of MPN. The aim of this study was to analyze a population based MPN cohort for genetic variants with prognostic value that can guide clinical decisions. Methods: MPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy. Results: Mutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN. Discussion: In conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered.

Hypertension management in primary health care: a survey in eight regions of Sweden.

PURPOSE: To explore hypertension management in primary healthcare (PHC). DESIGN: Structured interviews of randomly selected PHC centres (PHCCs) from December 2019 to January 2021. SETTING: Seventy-six PHCCs in eight regions of Sweden. MAIN OUTCOME MEASURES: Staffing and organization of hypertension care. Methods of measuring blood pressure (BP), laboratory tests, registration of co-morbidities and lifestyle advice at diagnosis and follow-up. RESULTS: The management of hypertension varied among PHCCs. At diagnosis, most PHCCs (75%) used the sitting position at measurements, and only 13% routinely measured standing BP. One in three (33%) PHCCs never used home BP measurements and 25% only used manual measurements. The frequencies of laboratory analyses at diagnosis were similar in the PHCCs. At follow-up, fewer analyses were performed and the tests of lipids and microalbuminuria decreased from 95% to 45% (p < 0.001) and 61% to 43% (p = 0.001), respectively. Only one out of 76 PHCCs did not measure kidney function at routine follow-ups. Lifestyle, physical activity, food habits, smoking and alcohol use were assessed in ≥96% of patients at diagnosis. At follow-up, however, there were fewer assessments. Half of the PHCCs reported dedicated teams for hypertension, 82% of which were managed by nurses. There was a great inequality in the number of patients per tenured GP in the PHCCs (median 2500; range 1300-11300) patients. CONCLUSIONS: The management of hypertension varies in many respects between PHCCs in Sweden. This might lead to inequity in the care of patients with hypertension.

Hypertension is mainly handled in primary healthcare (PHC), and this study shows important dissimilarities in organization and clinical management.Several variants in techniques and measurements of blood pressure were found between PHC centres.Lifestyle, clinical and laboratory assessments decreased at follow-ups compared to at diagnosis, specifically for lipids, microalbuminuria and electrocardiograms.Nearly half of the PHC centres reported that they had dedicated hypertension teams.

Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity: Development and Validation of the Revised DIGIROP Clinical Decision Support Tool.

Importance: The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants. Objective: To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models. Design, Setting, and Participants: This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023. Main Outcomes and Measures: Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed. Results: Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, -0.9 weeks; 95% CI, -1.5 to -0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6% (95% CI, 45.6-47.5) for the prescreen model and 76.9% (95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38% (95% CI, 32-46) for DIGIROP prescreen, 53% (95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46% (95% CI, 39-53) for WINROP. Conclusion and Relevance: Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.

Rotavirus infections and their genotype distribution in Rwanda before and after the introduction of rotavirus vaccination.

Rotavirus vaccination has reduced mortality and hospital admissions due to rotavirus diarrhoea, but its effect on rotavirus infections and the impact of rotavirus genotypes are still unclear. Real-time PCR was used to detect rotavirus and other pathogens in faeces samples from children below five years of age with acute diarrhoea, collected before (n = 827) and after (n = 807, 92% vaccinated) the introduction of vaccination in Rwanda in 2012. Rotavirus was genotyped by targeting VP7 to identify G1, G2, G3, G4, G9 and G12 and VP4 to identify P[4], P[6] and P[8]. In vaccinated children, rotavirus infections were rarer (34% vs. 47%) below 12 months of age, severe dehydration was less frequent, and rotavirus was more often found as a co-infecting agent. (79% vs 67%, p = 0.004). Norovirus genogroup II, astrovirus, and sapovirus were significantly more often detected in vaccinated children. The predominant rotavirus genotypes were G2P[4] and G12P[6] in 2009-2010 (50% and 12%), G9P[8] and G1P[8] in 2011-2012 (51% and 22%), and G12P[8] in 2014-2015 (63%). Rotavirus vaccination in Rwanda has reduced the severity of rotavirus gastroenteritis and rotavirus infection frequency during the first year of life. Rotavirus infections were frequent in vaccinated children with diarrhoea, often as co-pathogen. Rotavirus genotype changes might be unrelated to vaccination because shifts were observed also before its introduction.

Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection.

Background: Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. Methods: We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or ≥3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). Results: In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4+ T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or ≥3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4+ T-cell strata after 1 or ≥3 (median, 6.6) years of ART. Conclusions: In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4+ T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.

[Survival and prematurity-related neonatal diagnoses among children born before 24 gestational weeks in Sweden 2007-2018]. / Allt fler barn födda före vecka 24 överlever, men sjukligheten är hög.

Children born before 24 gestational weeks had high neonatal morbidity and a majority had one or more neurodevelopmental disorders in addition to somatic diagnoses in childhood. Active Swedish perinatal care of infants with gestational age <24 weeks has resulted in a survival rate of more than 50 percent. Resuscitation of these immature infants is controversial, and some countries offer comfort care only. In a retrospective review of medical files and registries of 399 Swedish infants born before 24 gestational weeks, a majority had severe prematurity-related neonatal diagnoses. In childhood (2-13 years), 75 percent had at least one neurodevelopmental disorder and 88 percent had one or more prematurity-related somatic diagnosis (permanent or transient) that was likely to affect their quality of life. Long-term consequences for surviving infants should be considered in general recommendations as well as in parental information.

Normal neonatal TREC and KREC levels in early onset juvenile idiopathic arthritis.

OBJECTIVE: Dysregulated central tolerance predisposes to autoimmune diseases. Reduced thymic output as well as compromised central B cell tolerance checkpoints have been proposed in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate neonatal levels of T-cell receptor excision circles (TRECs) and kappa-deleting element excision circles (KRECs), as markers of T- and B-cell output at birth, in patients with early onset JIA. METHODS: TRECs and KRECs were quantitated by multiplex qPCR from dried blood spots (DBS), collected 2-5 days after birth, in 156 children with early onset JIA and in 312 matched controls. RESULTS: When analysed from neonatal dried blood spots, the median TREC level was 78 (IQR 55-113) in JIA cases and 88 (IQR 57-117) copies/well in controls. The median KREC level was 51 (IQR 35-69) and 53 (IQR 35-74) copies/well, in JIA cases and controls, respectively. Stratification by sex and age at disease onset did not reveal any difference in the levels of TRECs and KRECs. CONCLUSION: T- and B-cell output at birth, as measured by TREC and KREC levels in neonatal dried blood spots, does not differ in children with early onset JIA compared to controls.

Does problem-based learning improve patient empowerment and cardiac risk factors in patients with coronary heart disease in a Swedish primary care setting? A long-term prospective, randomised, parallel single randomised trial (COR-PRIM).

OBJECTIVES: To investigate long-term effects of a 1-year problem-based learning (PBL) on self-management and cardiac risk factors in patients with coronary heart disease (CHD). DESIGN: A prospective, randomised, parallel single centre trial. SETTINGS: Primary care settings in Sweden. PARTICIPANTS: 157 patients with stable CHD completed the study. Subjects with reading and writing impairments, mental illness or expected survival less than 1 year were excluded. INTERVENTION: Participants were randomised and assigned to receive either PBL (intervention) or home-sent patient information (control group). In this study, participants were followed up at baseline, 1, 3 and 5 years. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was patient empowerment (Swedish Coronary Empowerment Scale, SWE-CES) and secondary outcomes General Self-Efficacy Scale (GSES), self-rated health status (EQ-VAS), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), weight and smoking. Outcomes were adjusted for sociodemographic factors. RESULTS: The PBL intervention group resulted in a significant improved change in SWE-CES over the 5-year period (mean (M), 39.39; 95% CI 37.88 to 40.89) compared with the baseline (M 36.54; 95% CI 35.40 to 37.66). PBL intervention group increased HDL-C level (M 1.39; 95% CI 1.28 to 1.50) compared with baseline (M 1.24; 95% CI 1.15 to 1.33) and for EQ-VAS (M 77.33; 95% CI 73.21 to 81.45) compared with baseline (M 68.13; 95% CI 63.66 to 72.59) while these outcomes remained unchanged in the control group. There were no significant differences in BMI, weight or scores on GSES, neither between nor within groups over time. The overall proportion of smokers was significantly higher in the control group than in the experimental group. CONCLUSION: One-year PBL intervention had positive effect on patient empowerment, health status and HDL-C at a 5-year follow-up compared with the control group. PBL education aiming to improve patient empowerment in cardiac rehabilitation should account for sociodemographic factors. TRIAL REGISTRATION NUMBER: NCT01462799.

Maternal human papillomavirus infection during pregnancy and preterm delivery: A mother-child cohort study in Norway and Sweden.

INTRODUCTION: Human papillomavirus (HPV) infection is common in women of reproductive age. Infection and inflammation are leading causes for preterm delivery (PTD), but the role of HPV infection in PTD and prelabor rupture of membranes (PROM) is unclear. We aimed to explore whether HPV infection during pregnancy in general, and high-risk-HPV (HR-HPV) infection specifically, increased the risk of PTD, preterm prelabor rupture of membranes (PPROM), PROM at term, and/or chorioamnionitis. MATERIAL AND METHODS: In pregnant women, who were participating in a prospective multicenter cohort study from a general population in Norway and Sweden (PreventADALL, ClinicalTrials.gov NCT02449850), HPV DNA was analyzed in available urine samples at mid-gestation (16-22 weeks) and at delivery, and in the placenta after delivery with Seegene Anyplex II HPV28 PCR assay. The risk of PTD, PPROM, PROM, and chorioamnionitis was analyzed using unadjusted and adjusted logistic regression analyses for any 28 HPV genotypes, including 12 HR-HPV genotypes, compared with HPV-negative women. Further, subgroups of HPV (low-risk/possibly HR-HPV, HR-HPV-non-16 and HR-HPV-16), persistence of HR-HPV from mid-gestation to delivery, HR-HPV-viral load, and presence of multiple HPV infections were analyzed for the obstetric outcomes. Samples for HPV analyses were available from 950 women with singleton pregnancies (mean age 32 years) at mid-gestation and in 753 also at delivery. RESULTS: At mid-gestation, 40% of women were positive for any HPV and 24% for HR-HPV. Of the 950 included women, 23 had PTD (2.4%), nine had PPROM (0.9%), and six had chorioamnionitis (0.6%). Of the term pregnancies, 25% involved PROM. The frequency of PTD was higher in HR-HPV-positive women (8/231, 3.5%) than in HPV-negative women (13/573, 2.3%) at mid-gestation, but the association was not statistically significant (odds ratio 1.55; 95% confidence interval 0.63-3.78). Neither any HPV nor subgroups of HPV at mid-gestation or delivery, nor persistence of HR-HPV was significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis. No HPV DNA was detected in placentas of women with PTD, PPROM or chorioamnionitis. CONCLUSIONS: HPV infection during pregnancy was not significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis among women from a general population with a low incidence of adverse obstetric outcomes.

Induction and subsequent decline of S1-specific T cell reactivity after COVID-19 vaccination.

We analyzed magnitude and duration of SARS-CoV-2-specific T cell responses in healthy, infection-naïve subjects receiving COVID-19 vaccines. Overlapping peptides spanning the N-terminal spike 1 (S1) domain of the spike protein triggered secretion of the T cell-derived cytokine interleukin-2 ex vivo in 94/94 whole blood samples from vaccinated subjects at levels exceeding those recorded in all 45 pre-vaccination samples. S1-specific T cell reactivity was stronger in vaccinated subjects compared with subjects recovering from natural COVID-19 and decayed with an estimated half-life of 134 days in the first six months after the 2nd vaccination. We conclude that COVID-19 vaccination induces robust T cell immunity that subsequently declines. EudraCT 2021-000349-42. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-000349-42.

Pre- and peripubertal sex steroids are inversely associated with birth weight in preterm boys.

OBJECTIVE: The relationship between sex hormone concentrations during childhood and birth weight (BW) is poorly understood. We aimed to investigate this relationship and the associations with anthropometric data at 5, 6, 7, 8, and 10 years of age in preterm boys. DESIGN: A prospective longitudinal single-centre study, including 58 boys with a BW of 1325-3320 g and gestational age (GA) of 32 + 2 to 36 + 6 weeks. PATIENTS AND MEASUREMENTS: Data on GA, BW and anthropometric data between 5 and 10 years of age were recorded. Testicular development was assessed at 8 and 10 years of age. Serum concentrations of sex steroids were analysed with gas chromatography-tandem mass spectrometry at 5-10 years and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with immunoassays at 10 years of age. RESULTS: At 8 years of age, testosterone and estrone correlated negatively with BW, (ρ = -0.35, p = .021) and (ρ = -0.34, p = .024), respectively. At 10 years of age, testosterone, dihydrotestosterone, estrone and estradiol correlated negatively with BW (ρ = -0.39, p = .010), (ρ = -0.38, p = .013), (ρ = -0.44, p = .003) and (ρ = -0.36, p = .019), respectively. Weight gain from birth correlated with testosterone at 5 years (ρ = 0.40, p = .002), 7 years (ρ = 0.30, p = .040), 8 years (ρ = 0.44, p = .003) and 10 years (ρ = 0.40, p = .008) of age. At 10 years of age, testosterone correlated with LH (ρ = 0.42, p = .006) and FSH (ρ = 0.33, p = .033) but not with testicular volume. CONCLUSIONS: Lower BW was associated with increased sex steroid concentrations from 8 years of age, independently of clinical signs of puberty.

Impact of pre-antiretroviral treatment HIV-RNA on time to successful virological suppression and subsequent virological failure - two nationwide, population-based cohort studies.

BACKGROUND: The impact of pre-antiretroviral treatment (ART) HIV-RNA on time to successful virological suppression and subsequent failure in HIV patients remains poorly investigated. METHODS: We used the Swedish InfCareHIV database and the Danish HIV Cohort Study to evaluate impact of pre-ART HIV-RNA on primary virological suppression (HIV-RNA < 50 copies/ml) and risk of secondary virological failure (two consecutive HIV-RNA > 200 copies/ml or one >1000 copies/ml). The study included 3366 Swedish and 2050 Danish ART naïve individuals who initiated ART in the period 2000-2018. We used Kaplan-Meier estimates and Cox regression analyses to estimate absolute risks and hazard ratios. RESULTS: In both cohorts, more than 95% of patients with a pre-ART HIV-RNA <100 000 copies/ml obtained virological suppression within the first year after ART initiation contrasting 74% (Sweden) and 86% (Denmark) in those with HIV-RNA >1 000 000 copies/ml. Almost all patients obtained virological suppression after four years irrespective of pre-ART HIV-RNA. In contrast, we observed no substantial impact of pre-ART HIV-RNA on risk of virological failure once virological suppression was obtained. CONCLUSION: High pre-ART HIV-RNA is strongly associated with increased time to successful virological suppression, but pre-ART HIV-RNA has no impact on risk of subsequent virological failure.