Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia.

BACKGROUND AND AIMS: Microvascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH). METHODS: Four groups of asymptomatic individuals aged 30-59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry. RESULTS: The groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups. CONCLUSIONS: Coronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.

Motor Development in Children with Cerebral Palsy in Sweden-A Population-Based Longitudinal Register Study.

The aim was to explore longitudinal motor development in children with cerebral palsy (CP) in Sweden with respect to the Gross Motor Function Classification System (GMFCS). In this national CP registry-based study, 2138 children aged 0.5-19 years participated (42% girls). The distribution with respect to GMFCS was I: 49%, II: 16%, III: 10%, IV: 14%, and V: 11%. In total, 5538 assessments (mean 2.7, min-max: 1-9) with the Gross Motor Function Measure-66 were included. Data were analysed using non-linear mixed-effects regression models, and the Stable Limit Model was selected to fit data. Five distinct curves of predicted gross motor development with respect to GMFCS levels were obtained. The achieved motor development was maintained over time. The estimated average GMFM-66 limit and the average age when 90% of the expected limits were reached were at GMFCS I: 88 at age 4.5; GMFCS II: 71 at age 4.2; GMFCS III: 54 at age 3.1; GMFCS IV: 38 at age 2.6, and at GMFCS V: 18 at age 0.9. In conclusion, this is the first national population-based study following motor development in CP. Five distinct curves reported in previous controlled research studies were confirmed. Our study adds knowledge about motor development captured in children's everyday context.

Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial.

BACKGROUND: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration. METHODS: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 µg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery. RESULTS: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly. CONCLUSION: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study.

BACKGROUND: Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer's disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms. OBJECTIVE: To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment. METHODS: A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users. RESULTS: Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent. CONCLUSIONS: Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses.

Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018: A Nationwide Retrospective Cohort Study.

Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.

Socioeconomic status is associated with process times in the emergency department for patients with chest pain.

Objective: Emergency department length of stay (EDLOS) is linked to crowding and patient outcomes whereas worse prognosis in low socioeconomic status remains poorly understood. We studied whether income was associated with ED process times among patients with chest pain. Methods: This was a registry-based cohort study on 124,980 patients arriving at 14 Swedish EDs between 2015 and 2019 with chest pain as their chief complaint. Individual-level sociodemographic and clinical data were linked from multiple national registries. The associations between disposable income quintiles, whether the time to physician assessment exceeded triage priority recommendations as well as EDLOS were evaluated using crude and multivariable regression models adjusted for age, gender, sociodemographic variables, and ED-management circumstances. Results: Patients with the lowest income were more likely to be assessed by physician later than triage recommendations (crude odds ratio [OR] 1.25 (95% confidence interval [CI] 1.20-1.29) and have an EDLOS exceeding 6 h (crude OR 1.22 (95% CI 1.17-1.27). Among patients subsequently diagnosed with major adverse cardiac events, patients with the lowest income were more likely to be assessed by a physician later than triage recommendations, crude OR 1.19 (95% CI 1.02-1.40). In the fully adjusted model, the average EDLOS was 13 min (5.6%) longer among patients in the lowest income quintile, 4:11 [h:min], (95% CI 4:08-4:13), compared to patients in the highest income quintile, 3:58 (95% CI 3:56-4:00). Conclusions: Among ED chest pain patients, low income was associated with longer time to physician than recommended by triage and longer EDLOS. Longer process times may have a negative impact due to crowding in the ED and delay diagnosis and timely treatment of the individual patient.

Effect of Internet-Delivered Emotion Regulation Individual Therapy for Adolescents With Nonsuicidal Self-Injury Disorder: A Randomized Clinical Trial.

Importance: Nonsuicidal self-injury is prevalent in adolescence and associated with adverse clinical outcomes. Effective interventions that are brief, transportable, and scalable are lacking. Objective: To test the hypotheses that an internet-delivered emotion regulation individual therapy for adolescents delivered adjunctive to treatment as usual is superior to treatment as usual only in reducing nonsuicidal self-injury and that improvements in emotion regulation mediate these treatment effects. Design, Setting, and Participants: This 3-site, single-masked, randomized superiority trial enrolled participants from November 20, 2017, to April 9, 2020. Eligible participants were aged between 13 and 17 years and met diagnostic criteria for nonsuicidal self-injury disorder; they were enrolled as a mixed cohort of consecutive patients and volunteers. Parents participated in parallel to their children. The primary end point was at 1 month after treatment. Participants were followed up at 3 months posttreatment. Data collection ended in January 2021. Interventions: Twelve weeks of therapist-guided, internet-delivered emotion regulation individual therapy delivered adjunctive to treatment as usual vs treatment as usual only. Main Outcomes and Measures: Primary outcome was the youth version of the Deliberate Self-harm Inventory, both self-reported by participants prior to treatment, once every week during treatment, and for 4 weeks posttreatment, and clinician-rated by masked assessors prior to treatment and at 1 and 3 months posttreatment. Results: A total of 166 adolescents (mean [SD] age, 15.0 [1.2] years; 154 [92.8%] female) were randomized to internet-delivered emotion regulation therapy plus treatment as usual (84 participants) or treatment as usual only (82 participants). The experimental intervention was superior to the control condition in reducing clinician-rated nonsuicidal self-injury (82% vs 47% reduction; incidence rate ratio, 0.34; 95% CI, 0.20-0.57) from pretreatment to 1-month posttreatment. These results were maintained at 3-month posttreatment. Improvements in emotion dysregulation mediated improvements in self-injury during treatment. Conclusions and Relevance: In this randomized clinical trial, a 12-week, therapist-guided, internet-delivered emotion regulation therapy delivered adjunctive to treatment as usual was efficacious in reducing self-injury, and mediation analysis supported the theorized role of emotion regulation as the mechanism of change in this treatment. This treatment may increase availability of evidence-based psychological treatments for adolescents with nonsuicidal self-injury. Trial Registration: ClinicalTrials.gov Identifier: NCT03353961.

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.

Association Between CKD, Obesity, Cardiometabolic Risk Factors, and Severe COVID-19 Outcomes.

Introduction: Chronic kidney disease (CKD) is a risk factor for acquiring severe COVID-19, but underlying mechanisms are unknown. We aimed to study the risk associated with CKD for severe COVID-19 outcomes in relation to body mass index (BMI) and diabetes because they are common risk factors for both CKD and severe COVID-19. Methods: This nationwide case-control study with data from mandatory national registries included 4684 patients (cases) admitted to the intensive care units (ICUs) requiring mechanical ventilation and 46,840 population-based controls matched by age, sex, and district of residency. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between severe COVID-19 and exposures with adjustment for confounders, in subgroups by BMI, and matched by type 2 diabetes. Results: The median age was 64 years, and 27.7% were female. CKD was observed in 5.4% of the cases and 1.5% of the controls, whereas 1.9% and 0.3% had end-stage CKD, respectively. CKD was associated with severe COVID-19 (OR, 2.20 [95% CI, 1.85-2.62]), continuous renal replacement therapy (CRRT) in ICU (OR, 7.36 [95% CI, 5.39-10.05]), and death any time after ICU admission (OR, 2.51 [95% CI, 1.96-3.22]). The risk associated with CKD for severe COVID-19 did not differ significantly by weight but was higher in those without diabetes (OR, 2.76 [95% CI, 2.15-3.55]) than in those with diabetes (OR, 1.88 [95% CI, 1.37-2.59]). Conclusion: CKD, especially end-stage CKD, is an important risk factor for severe COVID-19 and death after ICU admission also in patients with normal BMI and without type 2 diabetes.

Association of metformin use and survival in patients with cutaneous melanoma and diabetes.

BACKGROUND: Metformin use has been associated with improved survival in patients with different types of cancer, but research regarding the effect of metformin on cutaneous melanoma (CM) survival is sparse and inconclusive. OBJECTIVES: To investigate the association between metformin use and survival among patients with CM and diabetes. METHODS: All adult patients with a primary invasive CM between 2007 and 2014 were identified in the Swedish Melanoma Registry and followed until death, or end of follow-up on 31 December 2017 in this population-based cohort study. Patients with both CM and type 2 diabetes mellitus were assessed further. Overall survival (OS) and melanoma-specific survival (MSS) were the primary endpoints. Cox proportional hazard models estimating crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used comparing peridiagnostic use vs. nonuse of metformin. Dose response was evaluated based on defined daily doses. RESULTS: Among a total of 23 507 patients, 1162 patients with CM and type 2 diabetes mellitus were included in the final cohort, with a median follow-up time of 4.1 years (interquartile range 2.4-6.1). Peridiagnostic metformin use was associated with a significantly decreased risk of death by any cause (HR 0.68, 95% CI 0.57-0.81). Cumulative pre- and postdiagnostic metformin use was also associated with improved OS: the HR for prediagnostic use was 0.90 (95% CI 0.86-0.95) for every 6 months of use and the HR for postdiagnostic use ranged from 0.98 (95% CI 0.97-0.98) for 0-6 months to 0.59 (0.49-0.70) for 24-30 months of use. No association was found for metformin use and MSS. CONCLUSIONS: Metformin use was associated with improved OS in patients with CM and diabetes regardless of timing (pre-, post- or peridiagnostic use) and followed a dose-response pattern. However, further research regarding the underlying mechanisms is warranted.

Immunohistopathology of oral mucosal chronic graft-versus-host disease severity and duration.

OBJECTIVE: Chronic graft-versus-host disease (cGVHD) is the main cause of late non-relapse mortality following hematopoietic cell transplantation. Oral mucosal (om-) cGVHD is common, but diagnosis and assessment rely on clinical interpretation and patient-reported symptoms. We investigated immunohistopathological profiles with respect to om-cGVHD severity disease duration. MATERIAL AND METHODS: Ninety-four transplant patients and 15 healthy controls (n = 212 biopsies) were investigated by quantitative immunohistochemistry for T cells (CD4, CD8, and CD5), B cells (CD19 and CD20), macrophages (CD68), and Langerhans cells (CD1a). RESULTS: We found significant increases in T (CD4, CD8) and monocytic (CD68) cells in om-cGVHD, and a notable absence of B (CD19 and CD20) cells. Histopathological activity correlated with increased CD4, CD8 and CD68. However, CD4 was associated with mild om-cGVHD, whereas CD8 and CD68 were found to be elevated in severe om-cGVHD. CD8 and CD68 levels were raised at disease onset, but during late phase, the predominant CD68 population was accompanied by CD4. CONCLUSION: Oral cGVHD is a heterogenous clinical disorder, but our knowledge of the underlying biology remains limited. We highlight the importance of CD4, CD8 and CD68 immune profiling, together with histological grading for the staging of oral cGVHD, to broaden our understanding of the biology and individual disease course.

Effects of primary hyperparathyroidism on oral health. A longitudinal register-based study.

OBJECTIVES: To analyze the effects of primary hyperparathyroidism on oral health and to investigate if the effects are linked to severity of the disease. SUBJECTS AND METHODS: This prospective cohort study involved 6151 primary hyperparathyroidism patients registered in the Scandinavian Quality Registry of Thyroid, Parathyroid, and Adrenal surgery and the National Cancer Register after parathyroidectomy (exposure) during 2011-2017 (patient cohort) and 60,654 individuals without primary hyperparathyroidism (reference cohort), matched by age, gender, and county of resident at the date of parathyroidectomy. The outcomes were tooth extractions and periodontal interventions. The risk for the outcomes was assessed by Poisson regression models. RESULTS: After adjusting for covariates, the patient cohort had a higher incidence rate of tooth extraction during the two-year period after parathyroidectomy (IRR = 1.15; 95% CI = 1.01-1.31), but a lower incidence rate of periodontal interventions during the four- to six-year period after parathyroidectomy (IRR = 0.88; 95% CI = 0.79-0.99). Furthermore, patients with more severe primary hyperparathyroidism were more likely to have tooth extractions and periodontal interventions after parathyroidectomy. CONCLUSIONS: The risk of tooth extraction increased slightly during the first two years after parathyroidectomy. Thereafter, the oral health effects subsided. Pre-surgical serum ionized calcium levels and adenoma weight may indicate negative dental outcomes after parathyroidectomy.

Fluid accumulation and major adverse kidney events in sepsis: a multicenter observational study.

BACKGROUND: Whether early fluid accumulation is a risk factor for adverse renal outcomes in septic intensive care unit (ICU) patients remains uncertain. We assessed the association between cumulative fluid balance and major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or sustained renal dysfunction, in such patients. METHODS: We performed a multicenter, retrospective observational study in 1834 septic patients admitted to five ICUs in three hospitals in Stockholm, Sweden. We used logistic regression analysis to assess the association between cumulative fluid balance during the first two days in ICU and subsequent risk of MAKE30, adjusted for demographic factors, comorbidities, baseline creatinine, illness severity variables, haemodynamic characteristics, chloride exposure and nephrotoxic drug exposure. We assessed the strength of significant exposure variables using a relative importance analysis. RESULTS: Overall, 519 (28.3%) patients developed MAKE30. Median (IQR) cumulative fluid balance was 5.3 (2.8-8.1) l in the MAKE30 group and 4.1 (1.9-6.8) l in the no MAKE30 group, with non-resuscitation fluids contributing to approximately half of total fluid input in each group. The adjusted odds ratio for MAKE30 was 1.05 (95% CI 1.02-1.09) per litre cumulative fluid balance. On relative importance analysis, the strongest factors regarding MAKE30 were, in decreasing order, baseline creatinine, cumulative fluid balance, and age. In the secondary outcome analysis, the adjusted odds ratio for dialysis or sustained renal dysfunction was 1.06 (95% CI 1.01-1.11) per litre cumulative fluid balance. On separate sensitivity analyses, lower urine output and early acute kidney injury, respectively, were independently associated with MAKE30, whereas higher fluid input was not. CONCLUSIONS: In ICU patients with sepsis, a higher cumulative fluid balance after 2 days in ICU was associated with subsequent development of major adverse kidney events within 30 days, including death, renal replacement requirement, or persistent renal dysfunction.

Plasma Lipoprotein(a) measured in routine clinical care and the association with incident calcified aortic valve stenosis during a 14-year observational period.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is a causal cardiovascular risk factor recommended to be measured at least once in a lifetime. We aimed to establish the association between routinely measured Lp(a) levels and the development of incident calcified aortic valve stenosis (CAVS). METHODS: This retrospective registry based observational study includes all individuals who had their Lp(a) measured in clinical routine between 2003 and 2017 at Karolinska University Laboratory, Stockholm. Data on pre-existing medical conditions, pharmacological treatment and outcomes were retrieved from national patient registries. RESULTS: The study comprised 23,298 individuals of which 489 received a CAVS diagnosis during the study period. The CAVS group (71 ± 11 years, 62% males) had a larger cardiovascular burden than the group without CAVS (55 ± 17 years and 48% males). Individuals with CAVS had higher Lp(a) 90th percentile (117 mg/dL or 249 nmol/L) than those without (89 mg/dL or 179 nmol/L) (p < 0.001), a difference seen in both sexes. The incident rates of CAVS per 10,000 person-years was 22.3 for individuals at >90th Lp(a) percentile compared to 12.8 for the 0th - 50th percentiles (p < 0.001). Sex and age adjusted hazard ratios for development of incident CAVS was 1.53 (95% CI 1.08-2.15; p = 0.016) and for surgical or endovascular intervention for CAVS 1.42 (95% CI 0.73-2.79; p = 0.304) for individuals at Lp(a) > 90th percentile compared to the 0th - 50th percentile. CONCLUSIONS: Lp(a) measured in the clinical routine is higher in individuals with CAVS. An Lp(a) level above >90th percentile is associated with the development of incident CAVS during a 14-year observational period.

Peri- and postoperative outcomes in patients with endometriosis undergoing hysterectomy.

OBJECTIVES: To assess whether hysterectomy in patients with endometriosis is associated with higher proportion of complications compared with patients without, and whether route of hysterectomy affects this outcome. STUDY DESIGN: This is a population-based retrospective cohort study. Data were prospectively obtained from three National Swedish Registers. Patients undergoing a benign hysterectomy between 2015 and 2017 in Sweden were included in the study and were grouped according to a histology-proven diagnosis of endometriosis. Different hysterectomy modes were compared in patients with endometriosis. Perioperative data and postoperative complications up to 1 year after surgery were collected and measured. RESULTS: In all, 8,747 patients underwent a benign hysterectomy, and 1,166 patients with endometriosis was compared with 7,581 patients without. Patients with endometriosis had higher proportion of complications (adjusted Odds ratio aOR 1.2, 95% CI 1.0-1.4), were more often converted to abdominal hysterectomy (aOR 1.7, 95% CI 1.1-2.6), had higher estimated blood loss (EBL) (200-500 ml; aOR 1.8, 95% CI 1.4-2.3, >500 ml; aOR 3.1, 95% CI 2.2-4.4) and a longer operative time (1-2 h; aOR 2.1, 95% CI 1.4-3.2, >2 h; aOR 4.3, 95% CI 2.7-6.6) than endometriosis-free patients. The conversion rate was 13.8 times higher in total laparoscopic hysterectomy (TLH) compared with robotic-assisted laparoscopic hysterectomy (RATLH) (aOR 13.8, 95% CI 3.6-52.4). CONCLUSION: Higher conversion rate, higher EBL and higher frequency of complications were seen in patients with endometriosis. RATLH was associated with lower conversion rate compared to TLH.

Preserved renal function during long-term follow-up in children with chronic liver disease.

AIM: We have previously found well-maintained renal function in children with new-onset chronic liver disease. In this study, we investigated their renal function during long-term follow-up of the disease. METHODS: In a study of 289 children with chronic liver disease, renal function was investigated as glomerular filtration rate (GFR) measured as clearance of inulin or iohexol. Yearly change in GFR was calculated based on a linear mixed model. The data were analysed with regard to different subgroups of liver disease and with regard to the outcome. RESULTS: The initially well-preserved renal function remained so in most patients during the observation period, even in children with progressive liver disease leading to decompensation. The greatest fall in GFR occurred in patients with initial hyperfiltration. Cholestasis seemed to have a nephroprotective effect. CONCLUSION: Chronic liver disease in childhood seems to have less impact on renal function than believed earlier, at least as long as the liver function remains compensated. Regular renal check-ups remain an essential tool for optimal patient care. Hyperfiltration seems to predict decline in renal function. Otherwise no further reliable prognostic markers were found in patients whose liver disease was not decompensated.

Periodontal conditions and incident dementia: A nationwide Swedish cohort study.

BACKGROUND: Periodontal disease has been proposed as a putative etiological factor for dementia. The aim of this investigation was to compare the incidence of dementia in individuals with or without deep probing pocket depths (DPPD), serving as a proxy for periodontitis. METHODS: In this cohort study, conducted in Sweden, we identified 7992 individuals with DPPD and 29,182 matched individuals without DPPD (non-DPPD), using the Swedish Quality Registry for Caries and Periodontal Diseases (SKaPa). The two groups were followed for incident dementia (mean follow-up time was 7.6 years) based on data from the Swedish Dementia Registry (SveDem). The exposure-outcome relationship was explored by applying the Royston-Parmar (RP) flexible parametric survival model. RESULTS: The incidence of dementia in the two groups was similar. In the DPPD group 137 (1.7%) developed dementia and 470 (1.6%) in the non-DPPD group. The incidence rate of dementia was estimated to be 2.3 per 1000 person-years (95% confidence interval [CI] 1.9 to 2.7) in the DPPD group and 2.1 per 1000 person-years (95% CI 1.9 to 2.3) in the non-DPPD group. The RP model disclosed no association between DPPD and dementia incidence after controlling for potential confounders (the exponentiated coefficient was estimated to 1.13 [95% CI = 0.39 to 3.24]). CONCLUSION: In this sample, no association was revealed between deep probing pocket depths and the incidence of dementia.

Plasma lipoprotein(a) measured in the routine clinical care is associated to atherosclerotic cardiovascular disease during a 14-year follow-up.

AIMS: To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease. METHODS AND RESULTS: This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003-17. Outcome data were captured in national outcome registries. Levels of Lp(a) expressed in mass or molar units were examined separately. In adjusted Cox regression models, association between deciles of plasma Lp(a) concentrations, mortality, and cardiovascular outcomes were assessed. A total of 23 398 individuals [52% females, mean (standard deviation) age 55.5 (17.2) years, median Lp(a) levels 17 mg/dL or 19.5 nmol/L] were included. Individuals with an Lp(a) level >90th decile (>90 mg/dL or >180 nmol/L) had hazard ratios (95% confidence interval) of 1.25 (1.05-1.50) for major adverse cardiovascular events (P = 0.013), 1.37 (1.14-1.64) for atherosclerotic cardiovascular disease (P = 0.001), and 1.62 (1.28-2.05) for coronary artery disease (P ≤ 0.001), compared to individuals with Lp(a) ≤50th decile. No association between Lp(a) and mortality, peripheral artery disease, or ischaemic stroke was observed. CONCLUSION: High Lp(a) levels are associated with adverse cardiovascular disease outcomes also in individuals with Lp(a) measured in routine clinical care. This supports the 2019 ESC/EAS recommendation to measure Lp(a) at least once during lifetime to assess cardiovascular risk and implies the need for intensive preventive therapy in patients with elevated Lp(a).

Validating a model for medication-related dental outcomes in older people.

OBJECTIVES: To externally validate a model for medication-related dental outcomes in (a) a general older population with dementia and (b) a matched population without dementia. SUBJECTS AND METHODS: This validation study used population-based data from seven Swedish national registers (2008-2017). Individuals aged 60+ with dementia were matched to those without dementia on age, gender, and county of residence at the date of diagnosis (index date). The exposure was continuous use of xerogenic medications during the 3-year period before index date. The primary outcome was the number of tooth extraction and restorative procedures within 3 years after index date. RESULTS: A total of 334,220 individuals were included in the final sample. In the dementia cohort, the use of urological drugs (incidence rate ratio [IRR] 1.08, 95% CI 1.03-1.13), respiratory medicines (IRR 1.10, 95% CI 1.04-1.17), and proton-pump inhibitors (IRR 1.09, 95% CI 1.05-1.13) was associated with the primary outcome. In the non-dementia cohort, respiratory medicines (IRR 1.03, CI 1.00-1.05), proton-pump inhibitors (IRR 1.06, CI 1.04-1.08), opioids (IRR 1.05, CI 1.03-1.07), and antidepressants (IRR 1.06, CI 1.04-1.08) were associated with the primary outcome. CONCLUSIONS: Although there were differences in prescription patterns, the model performed similarly in both those with and without dementia.

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.