Biomarkers and Proteomics in Sarcomeric Hypertrophic Cardiomyopathy in the Young-FGF-21 Highly Associated with Overt Disease.

Background: Any difference in biomarkers between genotype-positive individuals with overt hypertrophic cardiomyopathy (HCM), and genotype-positive but phenotype-negative individuals (G+P-) in HCM-associated pathways might shed light on pathophysiological mechanisms. We studied this in young HCM patients. Methods: 29 HCM patients, 17 G+P--individuals, and age- and sex-matched controls were prospectively included. We analyzed 184 cardiovascular disease-associated proteins by two proximity extension assays, categorized into biological pathways, and analyzed with multivariate logistic regression analysis. Significant proteins were dichotomized into groups above/below median concentration in control group. Results: Dichotomized values of significant proteins showed high odds ratio (OR) in overt HCMphenotype for Fibroblast growth factor-21 (FGF-21) 10 (p = 0.001), P-selectin glycoprotein ligand-1 (PSGL-1) OR 8.6 (p = 0.005), and Galectin-9 (Gal-9) OR 5.91 (p = 0.004). For G+P-, however, angiopoietin-1 receptor (TIE2) was notably raised, OR 65.5 (p = 0.004), whereas metalloproteinase inhibitor 4 (TIMP4) involved in proteolysis, in contrast, had reduced OR 0.06 (p = 0.013). Conclusions: This study is one of the first in young HCM patients and G+P- individuals. We found significantly increased OR for HCM in FGF-21 involved in RAS-MAPK pathway, associated with cardiomyocyte hypertrophy. Upregulation of FGF-21 indicates involvement of the RAS-MAPK pathway in HCM regardless of genetic background, which is a novel finding.

Characterization of the Increase in Narcolepsy following the 2009 H1N1 Pandemic in Sweden.

(1) Background: In the context of the H1N1 pandemic and the Pandemrix vaccination campaign, an increased number of narcolepsy cases were noted in several countries. In Sweden, this phenomenon was attributed to the effect of the Pandemrix vaccination in the first place. Studies from China indicated that narcolepsy could occur as a consequence of the H1N1 infection itself. We performed an analysis of the increase, with a specific interest in age and sex distribution. We also aimed to validate the origin of the excess cases, post hoc. (2) Methods: Data for narcolepsy patients (ICD code G 47.4, both type 1 and type 2) distributed by sex and age at 5-year intervals, annually between 2005 and 2017, were retrieved from the National Patient Register. Information on the total population was collected from the Swedish Population Register. (3) Results: The number of narcolepsy cases increased markedly from 2009 to 2014 compared to the period before 2009. A particular increase in 2011 among children and teenagers was observed. The sex ratio did not change significantly during the study period. (4) Conclusions: Our results support an association between the increased prevalence of narcolepsy cases and Pandemrix vaccination, but the effect of the virus itself cannot be ruled out as a contributing factor.

Effects of education, income and employment on ICU and post-ICU survival - A nationwide Swedish cohort study of individual-level data with 1-year follow up.

PURPOSE: The aim of this study was to examine relationships between education, income, and employment (socioeconomic status, SES) and intensive care unit (ICU) survival and survival 1 year after discharge from ICU (Post-ICU survival). METHODS: Individual data from ICU patients were linked to register data of education level, disposable income, employment status, civil status, foreign background, comorbidities, and vital status. Associations between SES, ICU survival and 1-year post-ICU survival was analysed using Cox's regression. RESULTS: We included 58,279 adults (59% men, median length of stay in ICU 4.0 days, median SAPS3 score 61). Survival rates at discharge from ICU and one year after discharge were 88% and 63%, respectively. Risk of ICU death (Hazard ratios, HR) was significantly higher in unemployed and retired compared to patients who worked prior to admission (1.20; 95% CI: 1.10-1.30 and 1.15; (1.07-1.24), respectively. There was no consistent association between education, income and ICU death. Risk of post-ICU death decreased with greater income and was roughly 16% lower in the highest compared to lowest income quintile (HR 0.84; 0.79-0.88). Higher education levels appeared to be associated with reduced risk of death during the first year after ICU discharge. CONCLUSIONS: Significant relationships between low SES in the critically ill and increased risk of death indicate that it is important to identify and support patients with low SES to improve survival after intensive care. Studies of survival after critical illness need to account for participants SES.

Long-term mortality after self-inflicted burns.

BACKGROUND: Those with self-inflicted burns are a small but consistent group among burn patients, with large injuries and conflicting findings regarding their in-hospital mortality. Overall, burn survivors have a shorter life expectancy, as compared with national controls, but long-term mortality after self-inflicted burns is understudied. The aim of this retrospective study was to investigate possible differences in long-term mortality among survivors after self-inflicted and accidental burns. METHODS: All adult patients with burns admitted at the Linköping Burn Centre and discharged alive between 2000 and 2017 were included, and end of follow up was April 26, 2021. Those with unknown survival status at that time were excluded. A Cox proportional hazards regression model, adjusted for age and sex, was used to analyse long term mortality. RESULTS: Among the 930 patients included in this study, 37 had self-inflicted burns. Overall, median follow up period was 8.8 years and crude mortality was 24.7%. After adjustment for age and sex, self-inflicted burns were independently associated with long-term mortality, Hazard Ratio= 2.08 (95% CI 1.13-3.83). Post hoc analysis showed that the effect was most pronounced during the first years after discharge although it was noticeable over the whole study period. CONCLUSION: Long-term risk of mortality after discharge from a burn centre was higher in patients with self-inflicted burns than in patients with accidental burns. The effect was noticeable over the whole study period although it was most pronounced during the first years after discharge.

Insufficient use of menopausal hormone therapy in Swedish women with early or premature menopause caused by bilateral oophorectomy: a register-based study.

OBJECTIVE: To investigate the use of menopausal hormone therapy (MHT) in premenopausal women after bilateral oophorectomy. DESIGN: Retrospective register-based cohort study. SETTING: Sweden. POPULATION: Swedish women aged 35-44 years without malignancy who underwent bilateral oophorectomy in 2005-2020 were identified using The Swedish National Quality Register of Gynaecological Surgery (GynOp). METHODS: Data from GynOp were cross-linked with data on dispensed drugs extracted from the Swedish Prescribed Drug Register. MAIN OUTCOME MEASURES: Proportion of women dispensed MHT at least once within 1 year after surgery. Repeated treatment episodes were defined, and the proportion of 'person time' covered by dispensations was analysed. RESULTS: In total, 1231 of all women (n = 1706) were dispensed MHT at some point after surgery, with 1177 women dispensed MHT within 1 year. This proportion increased from 64% in 2005 to 84% in 2019 (p < 0.001). In the total population, 4537 'treatment years' transpired, corresponding to 43% of the mean time covered. In women dispensed MHT within 1 year, the proportion of time covered was 63%. CONCLUSIONS: Only 69% of all women without malignancy of any kind who underwent bilateral oophorectomy were dispensed MHT within 1 year after surgery, and the duration of treatment was limited. It is important to study further the reasons behind the low dispensation rate in this group to increase adherence to current treatment guidelines, improve quality of life, and avoid increased morbidity and mortality.

Fluoroquinolone-resistant Escherichia coli among the rectal flora is the predominant risk factor for severe infection after transrectal ultrasound-guided prostate biopsy: a prospective observational study.

BACKGROUND: Infection of the prostate gland following biopsy, usually with Escherichia coli, is a common complication, despite the use of antimicrobial prophylaxis. A fluoroquinolone (FQ) is commonly prescribed as prophylaxis. Worryingly, the rate of fluoroquinolone-resistant (FQ-R) E. coli species has been shown to be increasing. OBJECTIVE: This study aimed to identify risk factors associated with infection after transrectal ultrasound-guided prostate biopsy (TRUS-Bx). METHODS: This was a prospective study on patients undergoing TRUS-Bx in southeast Sweden. Prebiopsy rectal and urine cultures were obtained, and antimicrobial susceptibility and risk-group stratification were determined. Multivariate analyses were performed to identify independent risk factors for post-biopsy urinary tract infection (UTI) and FQ-R E. coli in the rectal flora. RESULTS: In all, 283 patients were included, of whom 18 (6.4%) developed post-TRUS-Bx UTIs. Of these, 10 (3.5%) had an UTI without systemic inflammatory response syndrome (SIRS) and 8 (2.8%) had a UTI with SIRS. Being in the medium- or high-risk groups of infectious complications was not an independent risk factor for UTI with SIRS after TRUS-Bx, but low-level FQ-resistance (minimum inhibitory concentration (MIC): 0.125-0.25 mg/L) or FQ-resistance (MIC > 0.5 mg/L) among E. coli in the faecal flora was. Risk for SIRS increased in parallel with increasing degrees of FQ-resistance. Significant risk factor for harbouring FQ-R E.coli was travelling outside Europe within the previous 12 months. CONCLUSION: The predominant risk factor for UTI with SIRS after TRUS-Bx was FQ-R E. coli among the faecal flora. The difficulty in identifying this type of risk factor demonstrates a need for studies on the development of a general approach either with rectal swab culture for targeted prophylaxis, or prior rectal preparation with a bactericidal agent such as povidone-iodine before TRUS-Bx to reduce the risk of FQ-R E. coli-related infection.

Trends in the incidence, prevalence and sales volume of menopausal hormone therapy in Sweden from 2000 to 2021.

OBJECTIVES: To describe the trends in the prevalence of use menopausal hormone therapy (MHT) in Sweden over the period 2000-2021 and to analyse the impact of different lengths of run-in on the calculated incident use. STUDY DESIGN: Individual-level data on MHT dispensations for 2.5 million women aged 45-69 years for the period 2006-2021 were analysed. Aggregated sales volumes in defined daily dose (DDD) were available for the whole study period (2000-2021). MAIN OUTCOME MEASURES: One-year prevalence and one-year incidence (18-month run-in) per 1000 women and DDD per 1000 women per day of MHT were the main outcome measures. The predictive values for incidence representing first-ever use of MHT were calculated for different run-in periods, which is a defined period without dispensations. RESULTS: Both the DDD, from 2000, and the prevalence, from 2006, decreased by over 80 % in women aged 50-54 years, until 2010, when the use of MHT stabilised. The predictive value for incident users to be first-ever users was 88 % in women aged 50-54 years, with a run-in of 18 months, in 2021. The incidence was stable between 2007 and 2016. From 2017 the incidence increased, being most pronounced for women close to menopause. CONCLUSIONS: MHT use decreased significantly after the turn of the century, but has increased since 2017. A run-in period of 18 months was found suitable and reliable for defining incident users of MHT in the age intervals closest to menopause. Incidence seems to be a more sensitive measure than prevalence or DDD for the early detection of changes in trends in prescriptions of MHT.

Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is associated with aberrant emotional information processing while little is known about non-emotional cognitive processing biases. The dorsal anterior cingulate cortex (dACC) has been implicated in SAD neuropathology and is activated both by emotional and non-affective cognitive challenges like the Multisource Interference Task (MSIT). METHODS: Here, we used fMRI to compare dACC activity and test performance during MSIT in 69 SAD patients and 38 healthy controls. In addition to patient-control comparisons, we examined whether neural activity in the dACC correlated with social anxiety, trait anxiety or depression levels. RESULTS: The MSIT activated the dACC as expected but with no differences in task performance or neural reactivity between SAD patients and controls. There were no significant correlations between dACC activity and social or trait anxiety symptom severity. In patients, there was a significant negative correlation between dACC activity and depressive symptoms. CONCLUSIONS: In absence of affective challenge, we found no disorder-related cognitive profile in SAD patients since neither MSIT task performance nor dACC neural activity deviated in patients relative to controls.

Inventory study of an early pandemic COVID-19 cohort in South-Eastern Sweden, focusing on neurological manifestations.

BACKGROUND: Neurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection. The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of Östergötland in southeastern Sweden. METHODS: This is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. RESULTS: Seventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. CONCLUSION: Neurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

Incidence of self-reported pelvic pain and risk factors for pain 1 year after benign hysterectomy: A register study from the Swedish National Quality Registry for Gynecological Surgery.

INTRODUCTION: The primary aim of this study was to determine the incidence of patient-reported pain 1 year after hysterectomy for benign gynecological conditions in relation to occurrence of preoperative pain. The secondary aim was to analyze clinical risk factors for pain 1 year after the hysterectomy in women with and without preoperatively reported pelvic/lower abdominal pain. MATERIAL AND METHODS: This was a historical cohort study using data from the Swedish National Quality Registry for Gynecological Surgery on 16 694 benign hysterectomies. Data were analyzed using multivariable logistic regression models. RESULTS: One year after surgery, 22.4% of women with preoperative pain reported pelvic pain and 7.8% reported de novo pelvic pain. For those with preoperative pain younger age (adjusted odds ratio [aOR] 1.75, 95% confidence interval [CI] 1.38-2.23 and aOR 1.21, 95% CI 1.10-1.34 for women aged <35 and 35-44 years, respectively), not being gainfully employed (aOR 1.43, 95% CI 1.26-1.63), pelvic pain as the main symptom leading to hysterectomy (aOR 1.51, 95% CI 1.19-1.90), endometriosis (aOR 1.18, 95% CI 1.06-1.31), and laparoscopic hysterectomy (aOR 1.30, 95% CI 1.07-1.58), were clinically relevant independent risk factors for pelvic/lower abdominal pain 1 year after surgery, as were postoperative complications within 8 weeks after discharge. Meanwhile, clinically relevant independent risk factors for reporting de novo pain 1 year after surgery were younger age (aOR 2.05, 95% CI 1.08-3.86 and aOR 1.29, 95% CI 1.04-1.60 for women aged <35 and 35-44 years, respectively), and postoperative complications within 8 weeks after discharge. CONCLUSIONS: The incidence of pelvic pain and de novo pain 1 year after hysterectomy was relatively high. Women with and without reported preoperative pelvic/lower abdominal pain represented clinically different populations. The risk factors for pelvic pain seemed to differ in these two populations. The differences in risk factors could be taken into consideration in the preoperative counseling and in the decision-making concerning method of hysterectomy, provided that large well-designed studies confirm these risk factors.

Frailty is a stronger predictor of death in younger intensive care patients than in older patients: a prospective observational study.

BACKGROUND: While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages. METHODS: Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups. RESULTS: Patients were classified into predefined age groups (18-49 years (n = 241), 50-64 (n = 188), 65-79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P < 0.05). Frail patients had higher SAPS3, more treatment restrictions and higher ICU mortality. Frailty was associated with an increased risk of 180-day mortality in all age groups (HR 5.7 (95% CI 2.8-11.4), P < 0.05; 8.0 (4.0-16.2), P < 0.05; 4.1 (2.2-6.6), P < 0.05; 2.4 (1.1-5.0), P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50-64 (2.1 (1.1-3.1), P < 0.05). CONCLUSIONS: Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

Association Between Experimental Pain Thresholds and Trajectories of Postoperative Recovery Measures After Benign Hysterectomy.

Purpose: Quantitative sensory testing (QST) can be applied to quantify the sensitivity to different painful stimuli. This study aims to evaluate the association between preoperative pressure and thermal pain thresholds and trajectories of measurements of postoperative recovery (patient-reported daily maximum and average pain intensity, sum score of symptoms, and analgesic consumption) after benign hysterectomy. Patients and Methods: A prospective, longitudinal single-blinded, observational multicenter study was conducted in five hospitals in the southeast of Sweden between 2011 and 2017. A total of 406 women scheduled for abdominal or vaginal hysterectomy for benign conditions were enrolled in the study. QST measuring pressure (PPT), heat (HPT), and cold pain thresholds (CPT) were performed preoperatively. The cut-off levels for dichotomizing the pain thresholds (low/high) were set at the 25-percentile for PPT and HPT and the 75-percentile for CPT. The Swedish Postoperative Symptom Questionnaire was used to measure postoperative pain and other symptoms of discomfort (symptom sum score) on 13 occasions for six weeks postoperatively. Daily analgesic consumption of opioids and non-opioids was registered. Results: A CPT above the 75-percentile was associated with high postoperative maximum pain intensity (p = 0.04), high symptom sum score (p = 0.03) and greater consumption of non-opioids (p = 0.03). A HPT below the 25-percentile was only associated with greater consumption of non-opioids (p = 0.02). PPT was not associated with any of the outcome measures. Conclusion: CPT seemed to be predictive for postoperative pain and symptoms of discomfort after benign hysterectomy. Preoperative QST may be used to individualize the management of postoperative recovery for low pain threshold individuals.

Risk factors and outcome due to extended-spectrum ß-lactamase-producing uropathogenic Escherichia coli in community-onset bloodstream infections: A ten-year cohort study in Sweden.

OBJECTIVE: To study clinical outcome and risk factors associated with extended-spectrum ß-lactamase (ESBL)-producing uropathogenic Escherichia coli (UPEC) in community-onset bloodstream infections (CO-BSI). METHODS: This was a population-based cohort study including patients with pheno- and genotype-matched ESBL-producing E. coli and non-ESBL- E. coli in urine and blood samples collected in 2009-2018 in southeast Sweden. Seventy-seven episodes of ESBL-UPEC satisfying the inclusion criteria were matched 1:1 with 77 non-ESBL-UPEC for age, gender, and year of culture. RESULTS: The most common ST-type and ESBL gene was ST131 (55%), and blaCTX-M-15 (47%), respectively. Risk factors for ESBL-UPEC were: previous genitourinary invasive procedure (RR 4.66; p = 0.005) or history of ESBL-producing E. coli (RR 12.14; p = 0.024). There was significant difference between ESBL-UPEC and non-ESBL-UPEC regarding time to microbiologically appropriate antibiotic therapy (27:15 h vs. 02:14 h; p = <0.001) and hospital days (9 vs. 5; p = <0.001), but no difference in 30-day mortality (3% vs. 3%; p = >0.999) or sepsis within 36 hours (51% vs. 62%; p = 0.623) was observed. CONCLUSION: The predominant risk factors for ESBL-UPEC were history of ESBL-Ec infection and history of genitourinary invasive procedure. The overall mortality was low and the delay in appropriate antibiotic therapy did not increase the risk for 30-day mortality or risk for sepsis within 36 hours among patients infected with ESBL UPEC. However, these results must be regarded with some degree of caution due to the small sample size.

Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy.

Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [11C]DASB and [11C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo.

Impact of HbA1c Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study.

OBJECTIVE: To evaluate HbA1c followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS: In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA1c (wHbA1c) was calculated by integrating the area under all HbA1c values. Complications were analyzed in relation to wHbA1c categorized into five levels. RESULTS: After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA1c did not develop PDR or macroalbuminuria. The lowest wHbA1c values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA1c, being 74% and 44% in the highest category, wHbA1c >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years' duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA1c values. CONCLUSIONS: wHbA1c followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA1c <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.

Impact of persistent peripheral neuropathy on health-related quality of life among early-stage breast cancer survivors: a population-based cross-sectional study.

BACKGROUND: We explored the impact of persistent sensory and motor taxane-induced peripheral neuropathy (TIPN) symptoms on health-related quality of life (HRQL) among early-stage breast cancer survivors (ESBCS). METHODS: A population-based cohort of 884 residual-free ESBCS received a postal questionnaire, including the EORTC chemotherapy-induced PN (CIPN20) and the EORTC QLQ-C30 instruments. Mean scores of QLQ-C30 scales among ESBCS with and without TIPN were calculated and adjusted for confounding factors (age, lifestyle factors, co-morbidities; linear regression analyses). Interpretation of QLQ-C30 results were based on guidelines. RESULTS: Response rate was 79%, and 646 survivors were included in the analysis. In median, 3.6 (1.5-7.3) years had elapsed post-taxane treatment. All TIPN symptoms had a significant impact on global QoL, which worsened with increased severity of TIPN. Between 29.5% and 93.3% of ESBCS with moderate-severe TIPN reported a clinical important impairment of functioning and personal finances, 64.3-85.7% reporting "difficulty walking because of foot drop," and 53.1-81.3% reporting "problems standing/walking because of difficulty feeling ground under feet" had impaired functioning/finances. The difference in mean scores between affected and non-affected survivors was highest for "numbness in toes/feet" and "difficulty walking because of foot drop." Moderate-severe "difficulty climbing stairs or getting out of chair because of weakness of legs" and "problems standing/walking because of difficulty feeling ground under feet" were associated with the largest clinically important differences on all scales. CONCLUSION: Persistent sensory and motor TIPN is associated with clinically relevant impairment of global QoL, functioning, and personal finances among ESBCS, which increased with level of TIPN severity.

Safety and pharmacokinetics-pharmacodynamics of a shorter tuberculosis treatment with high-dose pyrazinamide and rifampicin: a study protocol of a phase II clinical trial (HighShort-RP).

INTRODUCTION: Increased dosing of rifampicin and pyrazinamide seems a viable strategy to shorten treatment and prevent relapse of drug-susceptible tuberculosis (TB), but safety and efficacy remains to be confirmed. This clinical trial aims to explore safety and pharmacokinetics-pharmacodynamics of a high-dose pyrazinamide-rifampicin regimen. METHODS AND ANALYSIS: Adult patients with pulmonary TB admitted to six hospitals in Sweden and subjected to receive first-line treatment are included. Patients are randomised (1:3) to either 6-month standardised TB treatment or a 4-month regimen based on high-dose pyrazinamide (40 mg/kg) and rifampicin (35 mg/kg) along with standard doses of isoniazid and ethambutol. Plasma samples for measurement of drug exposure determined by liquid chromatography tandem-mass spectrometry are obtained at 0, 1, 2, 4, 6, 8, 12 and 24 hours, at day 1 and 14. Maximal drug concentration (Cmax) and area under the concentration-time curve (AUC0-24h) are estimated by non-compartmental analysis. Conditions for early model-informed precision dosing of high-dose pyrazinamide-rifampicin are pharmacometrically explored. Adverse drug effects are monitored throughout the study and graded according to Common Terminology Criteria for Adverse Events V.5.0. Early bactericidal activity is assessed by time to positivity in BACTEC MGIT 960 of induced sputum collected at day 0, 5, 8, 15 and week 8. Minimum inhibitory concentrations of first-line drugs are determined using broth microdilution. Disease severity is assessed with X-ray grading and a validated clinical scoring tool (TBscore II). Clinical outcome is registered according to WHO definitions (2020) in addition to occurrence of relapse after end of treatment. Primary endpoint is pyrazinamide AUC0-24h and main secondary endpoint is safety. ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. Informed written consent is collected before study enrolment. The study results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04694586.

ABO blood group and effects on ventilatory time, length of stay and mortality in major burns a retrospective observational outcome study.

Blood group has been found to be important in the development of many diseases and the outcome of several disease processes, especially cardiovascular morbidity and mortality, such as caused by trauma and sepsis. The main reason is claimed to be related to glycobiology and effects mediated through the endothelium. This study investigated the possible effect of blood group (ABO) on burn care outcome. Burn outcome prediction models are extremely accurate and as such can be used to identify outcome effects even in single centre settings. In this retrospective risk adjusted observational study, we investigated the effect of ABO blood group on ventilatory time, length of hospital stay (LOS), and 90 day mortality among patients with burns. RESULTS: A total of 225 patients were included (2008-2019) with median TBSA of 26%; interquartile range (IQR) of 20-37%; median age 45 years (IQR 22-65 years); median Baux score (age + TBSA%); 76 (IQR 53- 97); 168 (75%) were male; median duration of hospital stay was 31 days (IQR 19-56); a total of 138 (61%) received treatment with mechanical ventilation; and 29 (13%) died. In a multivariable regression model, we were unable to isolate any significant effect of any blood group (O, A, B, AB) on the outcome measures studied (ventilatory time, LOS, and mortality). IN SUMMARY: contrary to many other major areas of disease in which ABO blood groups affect outcome, we were unable to find any such effect on patients with burns. Given the precision of the outcome models presented (AUC 0.93) any such an effect, if missed due to the limited study cohort, may be considered limited and to have only a minor clinical impact.

Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography.

ABSTRACT: Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.

Clinical Frailty Scale classes are independently associated with 6-month mortality for patients after acute myocardial infarction.

AIMS: Data on the prognostic value of frailty to guide clinical decision-making for patients with myocardial infarction (MI) are scarce. To analyse the association between frailty classification, treatment patterns, in-hospital outcomes, and 6-month mortality in a large population of patients with MI. METHODS AND RESULTS: An observational, multicentre study with a retrospective analysis of prospectively collected data using the SWEDEHEART registry. In total, 3381 MI patients with a level of frailty assessed using the Clinical Frailty Scale (CFS-9) were included. Of these patients, 2509 (74.2%) were classified as non-vulnerable non-frail (CFS 1-3), 446 (13.2%) were vulnerable non-frail (CFS 4), and 426 (12.6%) were frail (CFS 5-9). Frailty and non-frail vulnerability were associated with worse in-hospital outcomes compared with non-frailty, i.e. higher rates of mortality (13.4% vs. 4.0% vs. 1.8%), cardiogenic shock (4.7% vs. 2.5% vs. 1.9%), and major bleeding (4.5% vs. 2.7% vs. 1.1%) (all P < 0.001), and less frequent use of evidence-based therapies. In Cox regression analyses, frailty was strongly and independently associated with 6-month mortality compared with non-frailty, after adjustment for age, sex, the GRACE risk score components, and other potential risk factors [hazard ratio (HR) 3.32, 95% confidence interval (CI) 2.30-4.79]. A similar pattern was seen for vulnerable non-frail patients (fully adjusted HR 2.07, 95% CI 1.41-3.02). CONCLUSION: Frailty assessed with the CFS was independently and strongly associated with all-cause 6-month mortality, also after comprehensive adjustment for baseline differences in other risk factors. Similarly, non-frail vulnerability was independently associated with higher mortality compared with those with preserved functional ability.