Changes in hepatitis C virus prevalence and incidence among people who inject drugs in the direct acting antiviral era.

BACKGROUND: The World Health Organization (WHO) has set a goal to eliminate hepatitis C virus (HCV) infection by 2030, including a 90% reduction of HCV incidence. With the introduction of a needle syringe program (NSP) in Stockholm, Sweden, and unrestricted availability of direct acting antiviral (DAA) treatment, we investigate the change of prevalence and incidence of HCV infection among people who inject drugs (PWID) over time. METHODS: All persons attending the Stockholm NSP 2013-2021 (n=4,138) were included. The prevalence of viremic HCV infection was investigated yearly. For incidence analysis, PWID at risk with at least one follow-up test were included. Participants were divided into naive defined as anti-HCV negative (n=791), and exposed, defined as anti-HCV positive with a negative HCV RNA (n=1,030). Risk factors for HCV infection were analyzed using parametric exponential proportional hazards regression models. RESULTS: The prevalence of viremic HCV infection decreased from 62% to 30% year 2013-2021 while the prevalence of cured after treatment increased from 0 to 22%, corresponding to 42% cured after treatment out of eligible in 2021. The overall incidence rate in naive was 16.9 (95% CI 15.0-19.0) and in exposed 12.8 (95% CI 11.6-14.2) per 100 person years (PY) and was not significantly reduced years 2013-2015 to 2020-2021 in either group. Risk factors for incident HCV infection in multivariable analysis were sharing needles/syringes, younger age, custody/prison past year, and homelessness, whereas opioid agonist treatment was protective. CONCLUSION: The prevalence of HCV was halved in PWID as unrestricted DAA treatment became available and NSP was established in Stockholm. However, overall incidence was not reduced. To meet the WHO incidence goal, targeting PWID with high injection risk behaviors for testing and treatment is essential, along with engagement in harm reduction services.

Validation of the Comprehensive Feeding Practices Questionnaire among parents of 5- to 7-year-old children in Sweden.

Introduction: Parents' behaviours towards food and mealtimes, also known as parental feeding practices, are important in the development of children's eating habits. The Comprehensive Feeding Practices Questionnaire (CFPQ) was designed to measure parental feeding practices. The aim of this study was to evaluate the validity of the CFPQ in Sweden and to assess how it performs across different groups of people. Methods: Data were from the baseline of a trial promoting children's healthy dietary and physical activity behaviours, the Healthy School Start Plus intervention, conducted in 17 schools in the Stockholm region in Sweden. The CFPQ was completed by 263 parents (59% mothers) of 173 children, aged 5 to 7 years. Exploratory factor analysis and the omega reliability test were performed to identify the underlying factors in the data. Invariance testing was used to investigate the equivalence of these factors across parental sex, parental education and children's weight status. Results: Five factors were identified: monitoring of children's food intake, pressure to eat, restriction of food, use of food for emotional regulation, and healthy eating guidance. All five factors were invariant across parental sex and education, though some questions were excluded to achieve invariance. The monitoring, pressure to eat and emotional regulation factors were invariant across children's weight status. Discussion: These results suggest that the CFPQ is valid for use in Sweden, amongst parents of children aged 5 to 7 years. The measurement invariance allows for comparisons of all five underlying factors across mothers and fathers and parental education levels, though across children's weight status for only three factors. Due to the importance of parental feeding practices throughout childhood, this questionnaire should also be validated in other age groups in Sweden.

Socioeconomic Disparities and Mediators for Recurrent Atherosclerotic Cardiovascular Disease Events After a First Myocardial Infarction.

BACKGROUND: Low socioeconomic status is associated with worse secondary prevention use and prognosis after myocardial infarction (MI). Actions for health equity improvements warrant identification of risk mediators. Therefore, we assessed mediators of the association between socioeconomic status and first recurrent atherosclerotic cardiovascular disease event (rASCVD) after MI. METHODS: In this cohort study on 1-year survivors of first-ever MI with Swedish universal health coverage ages 18 to 76 years, individual-level data from SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and linked national registries was collected from 2006 through 2020. Exposure was socioeconomic status by disposable income quintile (principal proxy), educational level, and marital status. The primary outcome was rASCVD and secondary outcomes were cardiovascular and all-cause mortality. We initially assessed the incremental attenuation of hazard ratios with 95% CIs in sequential multivariable models adding groups of potential mediators (ie, previous risk factors, acute presentation and infarct severity, initial therapies, and secondary prevention). Thereafter, the proportion of excess rASCVD associated with a low income mediated through nonparticipation in cardiac rehabilitation, suboptimal statin management, a cardiometabolic risk profile, persistent smoking, and blood pressure above target after MI were calculated using causal mediation analysis. RESULTS: Among 68 775 participants (73.8% men), 7064 rASCVD occurred during a mean 5.7-year follow-up. Income, adjusted for age, sex, and calendar year, was associated with rASCVD (hazard ratio, 1.63 [95% CI, 1.51-1.76] in the lowest versus highest income quintile). Risk attenuated most by adjustment for previous risk factors and by adding secondary prevention variables for a final model (hazard ratio, 1.38 [95% CI, 1.26-1.51]) in the lowest versus highest income quintile. The proportions of the excess 15-year rASCVD risk in the lowest income quintile mediated through nonparticipation in cardiac rehabilitation, cardiometabolic risk profile, persistent smoking, and poor blood pressure control were 3.3% (95% CI 2.1-4.8), 3.9% (95% CI, 2.9-5.5), 15.2% (95% 9.1-25.7), and 1.0% (95% CI 0.6-1.5), respectively. Risk mediation through optimal statin management was negligible. CONCLUSIONS: Nonparticipation in cardiac rehabilitation, a cardiometabolic risk profile, and persistent smoking mediate income-dependent prognosis after MI. In the absence of randomized trials, this causal inference approach may guide decisions to improve health equity.

Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19.

Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease.

Sweden's first Take-Home Naloxone program: participant characteristics, dose endpoints and predictors for overdose reversals.

BACKGROUND: Opioid overdoses are a growing concern, particularly among people who inject drugs. Sweden, with a comparatively high proportion of drug-related mortality, introduced its first Take-Home Naloxone (THN) program in 2018, at the Stockholm needle and syringe program (NSP). In this study we compare THN participant characteristics regarding refills and overdose reversals as well as investigate predictors associated with number of reversals. We also investigate interventions performed in overdose situations and endpoints for naloxone doses. METHODS: This was a prospective open inclusion cohort study conducted between January 24th 2018 and March 31st 2022 at the Stockholm NSP. Participants received THN, free of charge, after a training session and provided data regarding drug use and overdose experiences. During refill visits, participants reported if the naloxone was used for overdose reversal and, if so, responded to a ten-item questionnaire which included stating whether the naloxone recipient was the participant themselves or somebody else. Questionnaire data was combined with NSP database demographic data. Zero-inflated Poisson regression was applied to analyse predictors for number of reported overdose reversals. RESULTS: Among study participants (n = 1,295), 66.5% stated opioids as their primary drug, and 61.4% and 81.0% had previous experience of a personal or witnessed overdose, respectively. Overall, 44.0% of participants reported a total of 1,625 overdose reversals and the victim was known to have survived in 95.6% of cases. Stimulant use (aIRR 1.26; 95% CI 1.01, 1.58), benzodiazepine use (aIRR 1.75; 95% CI 1.1, 2.78) and homelessness (aIRR 1.35; 95% CI 1.06, 1.73) were predictors associated with an increased number of reported overdose reversals. Mortality was higher among those who reported at least one overdose reversal (HR 3.4; 95% CI 2.2, 5.2). CONCLUSIONS: An NSP's existent framework can be utilised to effectively implement a THN program, provide basic training and reach numerous high-risk individuals. During the four-year study, THN participants reversed a sizeable number of potentially fatal overdoses, of which many were reported by participants whose primary drug was not opioids. Naloxone refill rate was high, indicating that participants were motivated to maintain a supply of naloxone in case of future overdose events.

"I knew who I was this morning, but I've changed a few times since then": A study combining register and self-reported QoL data in assessing how response shift may occur in an injury population.

AIMS: The phenomenon of response shift may occur when people are exposed to a traumatic event and reevaluate the meaning of important aspects of their lives; a phenomenon that a traditional pre- and post-assessment cannot catch. Hence, the aim of the study was to increase the knowledge of how response shift may occur in people who have suffered an injury. METHODS: The current study is a register-based cohort study including 2512 participants. Data were retrieved from the Swedish LifeGene project and an online questionnaire, including the EQ5D. In order to analyze how response shift may occur, a "Then-test" and Structural Equation Model (SEM) were used. RESULTS: The results showed a clear indication of response shift through recalibration. The SEM analysis confirmed that participants significantly shifted their response between the post- and retrospective measurements. Significant differences were found for the VAS and for two of the five EQ5D dimensions: anxiety/depression and pain. CONCLUSION: This study provides additional knowledge to how response shift can occur in an injury population. This information can guide the next generation of QoL measures and be used as guidance for designing interventions for those suffering injuries. Furthermore, it may have an impact on how to interpret evaluations of interventions.

Temporal stability and responsiveness of a conditioned pain modulation test.

OBJECTIVES: Conditioned pain modulation is a commonly used quantitative sensory test, measuring endogenous pain control. The temporal stability of the test is questioned, and there is a lack of agreement on the effect of different pain conditions on the conditioned pain modulation response. Thus, an investigation of the temporal stability of a conditioned pain modulation test among patients suffering from persistent or recurrent neck pain is warranted. Further, an investigation into the difference between patients experiencing a clinically important improvement in pain and those not experiencing such an improvement will aid the understanding between changes in pain and the stability of the conditioned pain modulation test. METHODS: This study is based on a randomized controlled trial investigating the effect of home stretching exercises and spinal manipulative therapy vs. home stretching exercises alone. As no difference was found between the interventions, all participants were studied as a prospective cohort in this study, investigating the temporal stability of a conditioned pain modulation test. The cohort was also divided into responders with a minimally clinically important improvement in pain and those not experiencing such an improvement. RESULTS: Stable measurements of conditioned pain modulation were observed for all independent variables, with a mean change in individual CPM responses of 0.22 from baseline to one week with a standard deviation of 1.34, and -0.15 from the first to the second week with a standard deviation of 1.23. An Intraclass Correlation Coefficient (ICC3 - single, fixed rater) for CPM across the three time points yielded a coefficient of 0.54 (p<0.001). CONCLUSIONS: Patients with persistent or recurrent neck pain had stable CPM responses over a 2 week course of treatment irrespective of clinical response.

Are psychosocial work factors and work-home interference associated with time to first full return-to-work after sick leave due to common mental disorders?

OBJECTIVE: To (1) examine the time to first full return-to-work (RTW), and (2) investigate whether psychosocial work factors and work-home interference are associated with time to first full RTW after sick leave due to common mental disorders (CMDs). METHODS: The cohort study comprised 162 employees on sick leave due to CMDs participating in a two-armed cluster-randomised controlled trial in Sweden. Baseline data consisted of a web-based questionnaire and follow-up data of repeated text messages every fourth week for 12 months. The time to first full RTW was estimated using the Kaplan-Meier Estimator. Parametric Weibull survival models with interval-censored outcomes were used to determine associations between psychosocial work factors and work-home interference with time to first full RTW. In a post hoc analysis, time-interval differences in associations for 0- ≤ 6- versus > 6-12 months were tested. RESULTS: During the 12-month follow-up, n = 131 (80.9%) reported a first full RTW. The median time to this RTW was 16 weeks (95% CI 12; 20). High psychological job demands, high emotional job demands, high work-to-home interference (WHI), and low social job support were independently associated with a longer time to first full RTW. Time-interval differences were found for job control and emotional job demands. CONCLUSIONS: Psychosocial work demands and WHI are associated with a longer time to RTW after sick leave due to CMDs. Work organisations and rehabilitation practices should include accommodations for high psychological and emotional job demands during RTW, as well as pay attention to the risk of spill-over of high job demands into employees' private lives.

Prospective surveillance for cholangiocarcinoma in unselected individuals with primary sclerosing cholangitis.

BACKGROUND & AIMS: The evidence for hepatobiliary tumour surveillance in patients with primary sclerosing cholangitis (PSC) is scarce. In this study, we aimed to prospectively evaluate cholangiocarcinoma (CCA) surveillance with yearly MRI with cholangiopancreatography (MRI/MRCP) in a nationwide cohort. METHODS: In total, 512 patients with PSC from 11 Swedish hospitals were recruited. The study protocol included yearly clinical follow-ups, liver function tests and contrast-enhanced MRI/MRCP and carbohydrate antigen (CA) 19-9. Patients with severe/progressive bile duct changes on MRI/MRCP were further investigated with endoscopic retrograde cholangiopancreatography. Patients were followed for 5 years or until a diagnosis of CCA, liver transplantation (LT) and/or death. Risk factors associated with CCA were analysed with Cox regression. RESULTS: Eleven patients (2%) were diagnosed with CCA, and two (0.5%) with high-grade bile duct dysplasia. Severe/progressive bile duct changes on MRI/MRCP were detected in 122 patients (24%), of whom 10% had an underlying malignancy. The primary indication for LT (n = 54) was biliary dysplasia in nine patients (17%) and end-stage liver disease in 45 patients (83%), of whom three patients (7%) had unexpected malignancy in the explants. The median survival for patients with CCA was 13 months (3-22 months). Time to diagnosis of high-grade dysplasia and/or hepatobiliary malignancy was significantly associated with severe/progressive bile duct changes on MRI/MRCP (hazard ratio 10.50; 95% CI 2.49-44.31) and increased levels of CA19-9 (hazard ratio 1.00; 95% CI 1.00-1.01). CONCLUSION: In an unselected cohort of patients with PSC, yearly CA19-9 and MRI/MRCP surveillance followed by ERCP was ineffective in detecting cancer early enough to support long-term survival. Given the low occurrence of CCA, studies on individualised strategies for follow-up and improved diagnostic methods for PSC-related CCA are warranted. IMPACT AND IMPLICATIONS: A prospective nationwide 5-year study was conducted to evaluate yearly cholangiocarcinoma surveillance using MRI and CA19-9 in patients with primary sclerosing cholangitis. Only 2% of the patients were diagnosed with cholangiocarcinoma during follow-up and their prognosis remained poor despite surveillance. This surveillance strategy failed to detect cancer early enough to support long-term survival. Therefore, individualised strategies and improved diagnostic methods will be required to improve the early detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Are changes in pain associated with changes in heart rate variability in patients treated for recurrent or persistent neck pain?

BACKGROUND: Persistent or recurrent neck pain is associated with perturbations in the autonomic nervous system balance, and nociceptive stimulation has been seen to influence this balance. However, very few prospective studies have addressed the extent to which changes in pain associate with changes in autonomic cardiac regulation. Therefore, we investigated if changes in pain vary with changes in heart rate variability in a cohort of patients treated for persistent or recurrent neck pain. METHOD: This analysis is based on data from a randomized controlled trial in which participants were given home stretching exercises with or without spinal manipulative therapy for two weeks. As the effectiveness of the intervention (home stretching exercises and spinal manipulative therapy) was found to be equal to the control (home stretching exercises alone), all 127 participants were studied as one cohort in this analysis. During the intervention, pain levels were recorded using daily text messages, and heart rate variability was measured in the clinics three times over two weeks. Two approaches were used to classify patients based on changes in pain intensity: 1) Clinically important changes in pain were categorized as either "improved" or "not improved" and, 2) Pain development was measured using pain trajectories, constructed in a data driven approach. The association of pain categories and trajectories with changes in heart rate variability indices over time were then analysed using linear mixed models. RESULTS: Heart rate variability did not differ significantly between improved and not-improved patients, nor were there any associations with the different pain trajectories. CONCLUSIONS: In conclusion, changes in pain after home stretching exercises with or without spinal manipulative therapy over two weeks were not significantly associated with changes in heart rate variability for patients with persistent or recurrent neck pain. Future studies should rely on more frequent measurements of HRV during longer treatment periods. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov, registration number: NCT03576846.

Evaluation of Whole Brain Radiotherapy among Lung Cancer Patients with Brain Metastases in Relation to Health Care Level and Survival.

Whole-brain radiotherapy (WBRT) as a treatment for brain metastases has been questioned over the last years. This study aimed to evaluate health care levels and survival after WBRT in a cohort of lung cancer patients with brain metastases receiving WBRT in Stockholm, Sweden, from 2008 to 2019 (n = 384). If the patients were able to come home again was estimated using logistic regression and odds ratios (OR) and survival by using Cox regression. The median age in the cohort was 65.6 years, the median survival following WBRT was 2.4 months (interquartile range (IQR) 1.2-6.2 months), and 84 (22%) patients were not able to come home after treatment. Significantly more males could come home again after WBRT compared to women (OR = 0.37, 95%CI 0.20-0.68). Patients with performance status scores WHO 3-4 had a median survival of 1.0 months, hazard ratio (HR) = 4.69 (95%CI 3.31-6.64) versus WHO score 0-1. Patients admitted to a palliative ward before WBRT had a median survival of 0.85 months, HR = 2.26 (95%CI 1.53-3.34) versus being at home. In conclusion, patients treated with WBRT had a short median survival and 20% could not be discharged from the hospital following treatment. Significantly more women did not come home again.

Eccentric and Isometric Shoulder Rotation Strength and Range of Motion: Normative Values for Adolescent Competitive Tennis Players.

The aim of this cross-sectional study was to investigate isometric internal rotation (IR), external rotation (ER), abduction (ABD), and eccentric external rotation (eccER) shoulder strength and rotational range of motion (ROM) in adolescent male and female competitive tennis players. Additional aims of the study were to provide a tennis-specific normative database based on a large sample of players to deepen the knowledge regarding shoulder strength and ROM for adolescent competitive tennis players, and to discuss differences based on sex, age, and level of play. Shoulder strength and ROM was assessed in 301 adolescent competitive tennis players, 176 boys and 125 girls with a mean age of 14.6 and 14.4 years, respectively. Outcome variables of interest were isometric IR and ER strength, ABD strength, eccER shoulder strength, intermuscular strength ratios ER/IR and eccER/IR, IR ROM, ER ROM, and total range of motion (TROM). A General Linear Model two-way ANOVA was used to analyze differences in sex, age, and level of play. The findings of this study demonstrated age, side, and sex differences in the shoulder isometric strength, the eccER strength and ROM in adolescent competitive tennis players. Furthermore, when strength was expressed as ratios ER/IR and eccER/IR both sexes showed a lower ratio for eccER/IR in national players (0.95 ± 0.22 and 0.95 ± 0.23) compared to regional players (1.01 ± 0.32 and 1.07 ± 0.29) for male and female players, respectively. In conclusion, this paper presents a tennis-specific normative database for shoulder rotation strength and ROM in adolescent male and female competitive players. The key points in this evaluation are strength values normalized to body mass, intermuscular ratios, and TROM.

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes.

Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.

Recurrent surgery in uterine prolapse: A nationwide register study.

INTRODUCTION: One in three women with pelvic organ prolapse (POP) undergoing surgery have a relapse. Currently, no optimal surgical treatment has been identified for correcting a uterine prolapse. This population-based register study aims to compare the relapse rate in patients with uterine prolapse undergoing hysterectomy with suspension or uterine-sparing surgical procedures. MATERIAL AND METHODS: All women with uterine prolapse undergoing prolapse surgery in Sweden from January 1, 2015 to December 31, 2018, were identified from the Gynecological Operation Register (GynOp). The primary outcome was the number of recurrent POP surgeries up to December 31, 2020. RESULTS: Sacrospinous hysteropexy (SSHP) without graft and sacrohysteropexy (SHP) were associated with a significantly higher rate of recurrent POP surgery (SSHP without graft: adjusted odds ratio [aOR] 2.6, 95% CI 2.0-3.5; SHP aOR 2.6, 95% CI 1.8-3.7) and patients describing a sense of globe (SSHP without graft, aOR 2.0, 95% CI 1.6-2.6; SHP, aOR 1.8, 95% CI 1.1-3.1) compared with cervical amputation with uterosacral ligament fixation (Manchester procedure). There was no difference in the reoperation rate or sense of a globe between SSHP with graft and Manchester procedure. Patients undergoing SSHP without graft had a higher frequency of 1-year postoperative complications compared with Manchester procedure (aOR 2.0, 95% CI 1.6-2.6) and SHP (aOR 2.4, 95% CI 1.4-3.9). Moreover, the frequency of 1-year postoperative complications was higher in SSHP with graft (aOR 1.6, 95% CI 1.1-2.2) than in Manchester procedure. CONCLUSIONS: The Manchester procedure was associated with a low rate of recurrent POP surgery, symptomatic recurrence and low surgical morbidity compared with other surgical methods in women with uterine prolapse.

Vaginal vault prolapse and recurrent surgery: A nationwide observational cohort study.

INTRODUCTION: In surgical repair of pelvic organ prolapse the recurrence rate is about 30% and the importance of apical support was recently highlighted. In surgical randomized controlled studies, the external validity can be compromised because the surgical outcomes often depend on surgical volume. Therefore, we sought to study outcomes of surgical treatment in patients with vaginal vault prolapse in a nationwide setting with a variety of surgical volumes. MATERIAL AND METHODS: This is a nationwide cohort study. All patients with a vaginal vault prolapse undergoing surgery, between January 1, 2015 and December 31, 2018, were identified from the Swedish National Quality Register of Gynecological Surgery, GynOp. The primary outcome was the frequency of recurrent pelvic organ prolapse surgery within 2 years postoperatively. Secondary outcomes included patient-reported vaginal bulging, operative time, estimated blood loss and 1-year postoperative complications. RESULTS: In 1812 patients with vaginal vault prolapse, 538 (30%) had a sacrospinous ligament fixation (SSLF) with graft, 441 (24%) underwent SSLF without graft, and 200 (11%) underwent minimally invasive sacrocolpopexy (SCP) or sacrocervicopexy (SCerP). A significantly higher proportion of patients undergoing recurrent pelvic organ prolapse surgery was seen in SSLF without graft than in SSLF with graft (adjusted odds ratio [aOR] 2.2, 95% CI 1.4-3.6). Patient-reported sensation of vaginal bulging 1 year after surgery was higher in the SSLF group without graft than in the SSLF group with graft (aOR 1.9, 95% CI 1.3-2.8) and in the SCP/SCerP group (aOR 2.0, 95% CI 1.1-3.4). Finally, we found a significantly higher rate of complications 1 year after surgery in SSLF without graft (aOR 2.3, 95% CI 1.2-4.2) and in SSLF with graft (aOR 2.2, 95% CI 1.2-4.2) compared with SCP/SCerP. CONCLUSIONS: In patients with vaginal vault prolapse, SSLF without graft was associated with a higher frequency of recurrent pelvic organ prolapse surgery compared with SSLF with graft, and a higher subjective relapse rate compared with SCP/SCerP and SSLF with graft. Additionally, the complication rate 1 year after primary surgery was higher in SSLF both with and without graft than in SCP/SCerP.

Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care-A Post Hoc Analysis of the Randomized, Controlled Trial 'Palliative-D'.

In the randomized, placebo-controlled, double-blind trial 'Palliative-D', vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; -1.50 ESAS points (95%CI -2.57 to -0.43; p = 0.007) but not in women; -0.75 (95%CI -1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (-0.33 (95%CI -0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.

Infective Endocarditis Among High-risk Individuals Before and After the Cessation of Antibiotic Prophylaxis in Dentistry: A National Cohort Study.

BACKGROUND: A few years after the publication of the British guidelines, national recommendations were published by the Swedish Medical Products Agency in October 2012, promoting the cessation of antibiotic prophylaxis in dentistry for the prevention of infective endocarditis (IE). The aim of this study was to evaluate whether the incidence of oral streptococcal IE increased among high-risk individuals after October 2012. METHODS: This nationwide cohort study included all adult individuals (>17 years) living in Sweden from January 2008 to January 2018, with a diagnose code or surgical procedure code indicating high risk of IE. Cox proportional hazard models were performed to calculate adjusted ratios of oral streptococcal IE before and after October 2012 between high-risk individuals and references. RESULTS: This study found no increased incidence of oral streptococcal IE among high-risk individuals during the 5 years after the cessation, compared with before. Hazard rate ratios were 15.4 (95% confidence interval [CI]: 8.3-28.5) before and 20.7 (95% CI: 10.0-42.7) after October 2012 for prevalent high-risk individuals. Corresponding ratios for incident high-risk individuals were 66.8 (95% CI: 28.7-155.6) and 44.6 (95% CI: 22.9-86.9). Point estimates for interaction with time period were 1.4 (95% CI: .6-3.5) and 0.8 (95% CI: .5-1.3) for prevalent and incident high-risk individuals, respectively. CONCLUSION: The results suggest that the current Swedish recommendation not to administer antibiotic prophylaxis for the prevention of IE in dentistry has not led to an increased incidence of oral streptococcal IE among high-risk individuals.

Cardiovascular Family History Increases the Risk of Disease Recurrence After a First Myocardial Infarction.

Background Family history of atherosclerotic cardiovascular disease (ASCVD) is easily accessible and captures genetic cardiovascular risk, but its prognostic value in secondary prevention is unknown. Methods and Results We followed 25 615 patients registered in SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) from their 1-year revisit after a first-time myocardial infarction during 2005 to 2013, until December 31, 2018. Data on relatives, diagnoses and socioeconomics were extracted from national registers. The association between family history and recurrent ASCVD was studied with Cox proportional-hazard regression, adjusting for risk factors and socioeconomics. A family history of ASCVD was defined as hospitalization due to myocardial infarction, angina with coronary revascularization, stroke, or cardiovascular death in ≥1 parent or full sibling, with early-onset defined as disease-onset before 55 years in men and 65 in women. The additional discriminatory value of family history to Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was assessed with Harrell's C-index difference and reclassification was studied with continuous net reclassification improvement. Family history of early-onset ASCVD in ≥1 first-degree relative was present in 2.3% and was associated with recurrent ASCVD (hazard ratio [HR] 1.31; 95% CI, 1.17-1.47), fully adjusted for risk factors (HR, 1.22; 95% CI, 1.05-1.42). Early-onset family history improved the discriminatory ability of the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, with Harrell's C improving 0.003 points (95% CI, 0.001-0.005) from initial 0.587 (95% CI, 0.576-0.595) and improved reclassification (continuous net reclassification improvement 2.1%, P<0.001). Conclusions Family history of early-onset ASCVD is associated with recurrent ASCVD after myocardial infarction, independently of traditional risk factors and improves secondary risk prediction. This may identify patients to target for intensified secondary prevention.

Studies on CYP3A activity during the menstrual cycle as measured by urinary 6ß-hydroxycortisol/cortisol.

The 6ß-OH-cortisol/cortisol ratio (6ß-OHC/C) in urine is an endogenous marker of drug-metabolizing enzyme cytochrome P450 3A (CYP3A). The primary aim of this single center, prospective, non-interventional cohort study, was to investigate the variability of 6ß-OHC/C during the menstrual cycle. In addition, possible associations between the CYP3A activity and sex hormones, gut microbiota metabolite trimethylamine-N-Oxide (TMAO) and microRNA-27b, respectively, were investigated. Serum and urinary samples from healthy, regularly menstruating women followed for two menstrual cycles were analyzed. Twenty-six complete menstrual cycles including follicular, ovulatory, and luteal phase were defined based on hormone analyses in serum. 6ß-OHC/C were analyzed in urine and sex hormones, TMAO and miRNA-27b were analyzed in serum at the same time points. 6ß-OHC/C did not vary between the follicular, ovulatory, or luteal phases. There was a difference in the relative miRNA-27b expression between the follicular and ovulatory phase (p = .03). A significant association was found between 6ß-OHC/C and progesterone during the follicular (p = .005) and ovulatory (p = .01) phases (n = 26 for each phase). In addition, a significant association was found between the ratio and TMAO during the ovulatory (p = .02) and luteal (p = .002) phases. 6ß-OHC/C and gut microbiota TMAO were significantly associated (p = .003) when evaluating all values, for all phases (n = 78). Interestingly, the finding of an association between 6ß-OHC/C in urine and levels of TMAO in serum suggest that gut microbiota may affect CYP3A activity.

Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination.

Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.