Malpractice claims after antireflux surgery and paraesophageal hernia repair: a population-based analysis.

BACKGROUND: The complication rate of modern antireflux surgery or paraesophageal hernia repair is unknown, and previous estimates have been extrapolated from institutional cohorts. METHODS: A population-based retrospective cohort study of patient injury cases involving antireflux surgery and paraesophageal hernia repair from the Finnish National Patient Injury Centre (PIC) register between Jan 2010 and Dec 2020. Additionally, the baseline data of all the patients who underwent antireflux and paraesophageal hernia operations between Jan 2010 and Dec 2018 were collected from the Finnish national care register. RESULTS: During the study period, 5734 operations were performed, and the mean age of the patients was 54.9 ± 14.7 years, with 59.3% (n = 3402) being women. Out of all operations, 341 (5.9%) were revision antireflux or paraesophageal hernia repair procedures. Antireflux surgery was the primary operation for 79.9% (n = 4384) of patients, and paraesophageal hernia repair was the primary operation for 20.1% (n = 1101) of patients. A total of 92.5% (5302) of all the operations were laparoscopic. From 2010 to 2020, 60 patient injury claims were identified, with half (50.0%) of the claims being related to paraesophageal hernia repair. One of the claims was made due to an injury that resulted in a patient's death (1.7%). The mean Comprehensive Complication Index scores were 35.9 (± 20.7) and 47.6 (± 20.8) (p = 0.033) for antireflux surgery and paraesophageal hernia repair, respectively. Eleven (18.3%) of the claims pertained to redo surgery. CONCLUSIONS: The rate of antireflux surgery has diminished and the rate of paraesophageal hernia repair has risen in Finland during the era of minimally invasive surgery. Claims to the PIC remain rare, but claims regarding paraesophageal hernia repairs and redo surgery are overrepresented. Additionally, paraesophageal hernia repair is associated with more serious complications.

Lack of Statin Therapy and Outcomes After Ischemic Stroke: A Population-Based Study.

BACKGROUND: Statin treatment is effective at preventing adverse vascular events after ischemic stroke (IS). However, many patients fail to use statins after IS. We studied the impact of not using statins after IS on adverse outcomes. METHODS: IS patients (n=59 588) admitted to 20 Finnish hospitals were retrospectively studied. Study data were combined from national registries on hospital admissions, mortality, cancer diagnoses, prescription medication purchases, and permissions for special reimbursements for medications. Usage of prescription medication was defined as drug purchase within 90 days after hospital discharge. Ongoing statin use during follow-up was analyzed in 90-day intervals. Differences in baseline features, comorbidities, other medications, and recanalization therapies were balanced with inverse probability of treatment weighting. Median follow-up was 5.7 years. RESULTS: Statin therapy was not used by 27.1% of patients within 90 days after IS discharge, with women and older patients using statins less frequently. The average proportion of patients without ongoing statin during the 12-year follow-up was 36.0%. Patients without early statins had higher all-cause mortality at 1 year (7.5% versus 4.4% in patients who did use statins; hazard ratio [HR], 1.74 [CI, 1.61-1.87]) and 12 years (56.8% versus 48.6%; HR, 1.37 [CI, 1.33-1.41]). Cumulative incidence of major adverse cerebrovascular or cardiovascular event was higher at 1 year (subdistribution HR, 1.36 [CI, 1.29-1.43]) and 12 years (subdistribution HR, 1.21 [CI, 1.18-1.25]) without early statin use. Cardiovascular death, recurrent IS, and myocardial infarction were more frequent without early statin use. Early statin use was not associated with hemorrhagic stroke during follow-up. Lack of ongoing statin during follow-up was associated with risk of death in time-dependent analysis (adjusted HR, 3.03 [CI, 2.96-3.23]). CONCLUSIONS: Lack of statin treatment after IS is associated with adverse long-term outcomes. Measures to further improve timely statin use after IS are needed.

Adult-onset epilepsy and risk of traumatic brain injury: a nationwide cohort study.

BACKGROUND: A knowledge gap exists regarding the risk of traumatic brain injury (TBI) in patients with epilepsy. METHODS: Patients with adult-onset epilepsy during 2005-2018 in Finland were studied using retrospective longitudinal national registry-linkage design. Patients with epilepsy (n=35 686; 51% men; mean age 56.6 years) were 1:1 matched to non-epileptic controls by age, sex, comorbidity burden and cohort entry year. The primary outcome was TBI leading to admission or death, secondary outcomes were TBI admission, fatal TBI, acute neurosurgical operations (ANOs) for TBI and TBI recurrence. RESULTS: The cumulative rate of the primary endpoint was 1.2% at 1 year, 5.6% at 10 years and 7.3% at 14 years in the epilepsy group versus 2.9% at 14 years in the matched controls (HR=3.77; p<0.0001). Epilepsy was associated with increased risk of TBI admission (6.9% vs 2.7%; HR=3.96; p<0.0001), ANOs (1.3% vs 0.4%; HR=7.00; p<0.0001) and fatal TBI (1.3% vs 0.5%; HR=3.82; p<0.0001), during follow-up. Competing risk analyses confirmed the association of epilepsy with all outcomes (p<0.0001). Epilepsy was associated with TBI recurrence during follow-up (HR 1.72; p=0.002). CONCLUSION: Patients with adult-onset epilepsy have a significantly increased risk of severe and fatal TBI. The results underline the importance of TBI prevention in epilepsy.

Childhood manifestations of 22q11.2 deletion syndrome: A Finnish nationwide register-based cohort study.

AIM: The aim of the study was to describe the clinical manifestations of 22q11.2 deletion syndrome patients in the Finnish paediatric population. METHODS: Nationwide registry data including all diagnoses and procedures of every public hospital in Finland between 2004 and 2018 along with mortality and cancer registry data were retrieved. Patients born during the study period and with an ICD-10 code of D82.1 or Q87.06 were included as having 22q11.2 deletion syndrome. A control group was formed with patients born during the study period and with benign cardiac murmur diagnosed under the age of 1 year. RESULTS: We identified 100 pediatric patients with 22q11.2 deletion syndrome (54% males, median age at diagnosis <1 year, median follow-up 9 years). Cumulative mortality was 7.1%. Among patients with 22q11.2 deletion syndrome, 73.8% had congenital heart defects, 21.8% had cleft palate, 13.6% had hypocalcaemia, and 7.2% had immunodeficiencies. Furthermore, 29.6% were diagnosed with autoimmune diseases, 92.9% had infections, and 93.2% had neuropsychiatric and developmental issues during follow-up. Malignancy was found in 2.1% of the patients. CONCLUSION: The 22q11.2 deletion syndrome is associated with increased mortality and substantial multimorbidity in children. A structured multidisciplinary approach is necessary for managing patients with 22q11.2 deletion syndrome.

Anterior cruciate ligament reconstruction and concomitant procedures in Finland between 2004 and 2018 based on national registers.

BACKGROUND AND PURPOSE: We aimed to assess the incidence of anterior cruciate ligament reconstruction (ACLR) and concomitant procedures in Finland. PATIENTS AND METHODS: We identified all the patients who underwent ACLR between 2004 and 2018 in Finland using national registry data. Patients with an ICD-10 diagnosis code S83.5 and the NOMESCO operation codes NGE30 or NGE35 were included. We recorded the patient's age, sex, Charlson comorbidity index, and concomitant procedures. NGE30 or NGE35 was defined as the main procedure and all other procedures attached to this procedure were included as concomitant procedures. RESULTS: Our study included 37,224 ACLRs. The overall incidence of ACLR was 46 (95%CI 34-62) per 105 person-years. This increased from 38 per 105 person-years in 2004 to its peak of 53 in 2014 before decreasing to 47 by 2018. Male patients had a higher overall incidence of ACLR than female patients (61 [CI 47-78] vs. 32 [CI 22-45] per 105 person-years, respectively). However, this difference changed over time: for the males, a decrease in ACLR incidence was observed after 2014, whereas for the females, the trend increased throughout the study period. For both sexes, the highest incidence of ACLRs was in the age group 16-29 years (159 and 71 per 105 person-years, respectively). Concomitant procedures were performed at the time of ACLR in 32% of cases. CONCLUSION: While the total incidence of ACLR decreased slightly from 2014 to 2018, it increased among women over the full study period, which might be due to increased female participation in contact sports. Special attention should be given to girls' and women's ACL rupture prevention and treatment.

Long-term cardiovascular prognosis of patients with type 1 diabetes after myocardial infarction.

BACKGROUND: To explore long-term cardiovascular prognosis after myocardial infarction (MI) among patients with type 1 diabetes. METHODS: Patients with type 1 diabetes surviving 90 days after MI (n = 1508; 60% male, mean age = 62.1 years) or without any type of diabetes (n = 62,785) in Finland during 2005-2018 were retrospectively studied using multiple national registries. The primary outcome of interest was a combined major adverse cardiovascular event (MACE; cardiovascular death, recurrent MI, ischemic stroke, or heart failure hospitalization) studied with a competing risk Fine-Gray analyses. Median follow-up was 3.9 years (maximum 12 years). Differences between groups were balanced by multivariable adjustments and propensity score matching (n = 1401 patient pairs). RESULTS: Cumulative incidence of MACE after MI was higher in patients with type 1 diabetes (67.6%) compared to propensity score-matched patients without diabetes (46.0%) (sub-distribution hazard ratio [sHR]: 1.94; 95% confidence interval [CI]: 1.74-2.17; p < 0.0001). Probabilities of cardiovascular death (sHR 1.81; p < 0.0001), recurrent MI (sHR 1.91; p < 0.0001), ischemic stroke (sHR 1.50; p = 0.0003), and heart failure hospitalization (sHR 1.98; p < 0.0001) were higher in patients with type 1 diabetes. Incidence of MACE was higher in diabetes patients than in controls in subgroups of men and women, patients aged < 60 and ≥ 60 years, revascularized and non-revascularized patients, and patients with and without atrial fibrillation, heart failure, or malignancy. CONCLUSIONS: Patients with type 1 diabetes have notably poorer long-term cardiovascular prognosis after an MI compared to patients without diabetes. These results underline the importance of effective secondary prevention after MI in patients with type 1 diabetes.

Mortality after surgery for benign prostate hyperplasia: a nationwide cohort study.

PURPOSE: To investigate postoperative mortality rates and risk factors for mortality after surgical treatment of benign prostate hyperplasia (BPH). METHODS: All patients who underwent partial prostate excision/resection from 2004 to 2014 in Finland were retrospectively assessed for eligibility using a nationwide registry. Procedures were classified as transurethral resection of the prostate (TURP), laser vaporization of the prostate (laser), and open prostatectomy. Univariable and multivariable regression were used to analyze the association of age, Charlson comorbidity index (CCI), operation type, annual center operation volume, study era, atrial fibrillation, and prostate cancer diagnosis with 90 days postoperative mortality. RESULTS: Among the 39,320 patients, TURP was the most common operation type for lower urinary tract symptoms in all age groups. The overall 90 days postoperative mortality was 1.10%. Excess mortality in the 90 days postoperative period was less than 0.5% in all age groups. Postoperative mortality after laser operations was 0.59% and 1.16% after TURP (p = 0.035). Older age, CCI score, and atrial fibrillation were identified as risk factors for postoperative mortality. Prostate cancer diagnosis and the center's annual operation volume were not significantly associated with mortality. The most common underlying causes of death were malignancy (35.5%) and cardiac disease (30.9%). CONCLUSION: Elective urologic procedures for BPH are generally considered safe, but mortality increases with age. Laser operations may be associated with lower mortality rates than the gold standard TURP. Thus, operative risks and benefits must be carefully considered on a case-by-case basis. Further studies comparing operation types are needed.

Changing epidemiology of traumatic brain injury among the working-aged in Finland: Admissions and neurosurgical operations.

BACKGROUND: Recent studies from Finland have highlighted an increase in the incidence of traumatic brain injuries (TBI) in older age groups and high overall mortality. We performed a comprehensive study on the changing epidemiology of TBI focusing on the acute events in the Finnish working-age population. METHODS: Nationwide databases were searched for all emergency ward admissions with a TBI diagnosis for persons of 16-69 years of age during 2004-2018. RESULTS: In the Finnish working-age population, there were 52,487,099 person-years, 38,810 TBI-related hospital admissions, 4664 acute neurosurgical operations (ANO), and 2247 cases of in-hospital mortality (IHM). The TBI-related hospital admission incidence was 94/100,000 person-years in men, 44/100,000 in women, and 69/100,000 overall. The incidence rate of admissions increased in women, while in men and overall, the rate decreased. The incidence rate increased in the group of 60-69 years in both genders. Lowest incidence rates were observed in the age group of 30-39 years. Occurrence risk for TBI admission was higher in men in all age groups. Trends of ANOs decreased overall, while decompressive craniectomy was the only operation type in which a rise in incidence was found. Evacuation of acute subdural hematoma was the most common ANO. Mean length of stay and IHM rate halved during the study years. CONCLUSIONS: In Finland, the epidemiology of acute working-aged TBI has significantly changed. The rates of admission incidences, ANOs, and IHM nowadays represent the lower end of the range of these acute events reported in the western world.

Long-term outcomes of mechanical versus biological valve prosthesis in native mitral valve infective endocarditis.

Objectives. To study the long-term outcomes of mitral valve replacement with mechanical or biological valve prostheses in native mitral valve infective endocarditis patients. Desing. We conducted a retrospective, nationwide, multicenter cohort study with patients aged ≤70 years who were treated with mitral valve replacement for native mitral valve infective endocarditis in Finland between 2004 and 2017. Results. The endpoints were all-cause mortality, ischemic stroke, major bleeding, and mitral valve reoperations. The results were adjusted for baseline features (age, gender, comorbidities, history of drug abuse, concomitant surgeries, operational urgency, and surgical center). The median follow-up time was 6.1 years. The 12-year cumulative mortality rates were 36% for mechanical prostheses and 74% for biological prostheses (adj. HR 0.40; CI: 0.17-0.91; p = 0.03). At follow-up, the ischemic stroke had occurred in 19% of patients with mechanical prosthesis and 33% of those with a biological prosthesis (adj. p = 0.52). The major bleeding rates within the 12-year follow-up period were 30% for mechanical prosthesis and 13% for a biological prosthesis (adj. p = 0.29). The mitral valve reoperation rates were 13% for mechanical prosthesis and 12% for a biological prosthesis (adj. p = 0.50). Drug abuse history did not have a significant modifying impact on the results (interaction p = 0.51 for mortality and ≥0.13 for secondary outcomes). Conclusion. The use of mechanical mitral valve prosthesis is associated with lower long-term mortality compared to the biological prosthesis in non-elder native mitral valve infective endocarditis patients. The routine choice of biological mitral valve prostheses for this patient group is not supported by the results.

Cerebral Venous Thrombosis: Finnish Nationwide Trends.

BACKGROUND AND PURPOSE: Epidemiology of cerebral venous thrombosis (CVT) has been reported to be changing. Because long-term nationwide data are needed to confirm this, we studied CVT occurrence between 2005 and 2014 in Finland. METHODS: All acute CVT admissions were retrieved from a mandatory registry covering mainland Finland. Patients aged ≥18 years were included. One admission per patient was allowed. RESULTS: We identified 563 patients with CVT (56.5% women). Overall incidence was 1.32/100 000 (95% CI, 1.21-1.43) per year with a 5.0% annual increase. In people <55 years of age, incidence was 0.92/100 000 (0.76-1.10) for men and 1.65/100 000 (1.43-1.89) for women, whereas for those 55 years or older incidence was 1.61 (1.34-1.91) for men and 1.17 (0.96-1.41) for women. In-hospital mortality was 2.1% with no sex difference. One-year mortality was 7.9%. Long-term mortality was higher in men (adjusted hazard ratio, 1.61 [1.09-2.38]) and in older patients (1.95 [1.69-2.24]; per 10-year increment). CONCLUSIONS: Overall incidence of CVT in Finland was similar to that reported in the Netherlands and in Australia. There was a 5.0% yearly increase in the rate of admissions while in-hospital mortality was low. Sex-specific incidence rates differed markedly between younger and older people. Long-term mortality increased with age and was higher in men.

Patients with rheumatoid arthritis have impaired long-term outcomes after myocardial infarction: a nationwide case-control registry study.

OBJECTIVE: To investigate the long-term outcomes of patients with RA after myocardial infarction (MI). METHODS: All-comer, real-life MI patients with RA (n = 1614, mean age 74 years) were retrospectively compared with propensity score (1:5) matched MI patients without RA (n = 8070) in a multicentre, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients' outcomes were also studied. The median follow-up was 7.3 years. RESULTS: RA was associated with an increased 14-year mortality risk after MI compared with patients without RA [80.4% vs 72.3%; hazard ratio (HR) 1.25; CI: 1.16, 1.35; P <0.0001]. Patients with RA were at higher risk of new MI (HR 1.22; CI: 1.09, 1.36; P =0.0001) and revascularization (HR 1.28; CI: 1.10, 1.49; P =0.002) after discharge from index MI. Cumulative stroke rate after MI did not differ between RA and non-RA patients (P =0.322). RA duration and corticosteroid usage before MI, but not use of methotrexate or biologic antirheumatic drugs, were independently associated with higher mortality (P <0.001) and new MI (P =0.009). A higher dosage of corticosteroids prior to MI was independently associated with higher long-term mortality (P =0.002) and methotrexate usage with lower stroke rate (P =0.034). Serological status of RA was not associated with outcomes. CONCLUSION: RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population.

Infective endocarditis and outcomes of mitral valve replacement.

BACKGROUND: We investigated the long-term outcomes of mitral valve replacement (MVR) in native mitral valve infective endocarditis (IE). METHODS: Multicentre, population-based cohort register study consisted of 1233 consecutive adult patients treated with first-time MVR in Finland. Mitral valve IE was diagnosed in 170 of these patients. Propensity score matching resulted in 134 pairs with balanced baseline characteristics. The median follow-up was 6.1 years. RESULTS: Pre-operative native mitral valve IE was associated with an increased hazard of 10-year mortality (38.8% vs 30.5%; HR 2.13; CI 1.17-3.85; P = .013) after MVR. Occurrence of major bleeding was higher in IE patients (26.0%) vs non-IE patients (23.4%) during the 10-year follow-up (HR 2.80; CI 1.01-7.77; P = .048). Hospital admission duration after MVR was longer in IE patients (median 28 vs 11 days; P < .0001). Cumulative ischaemic stroke rate was similar between patient groups (12.1% in IE vs 15.1% in non-IE; P = .493). Re-sternotomy was performed in 13.4% of IE patients and 9.0% of non-IE patients (P = .261). CONCLUSIONS: Patients with native mitral valve IE have a higher risk of death and major bleeding after MVR than matched patients without IE. Results highlight the importance of complication prevention in these patients.

Surgical aortic valve replacement and infective endocarditis.

BACKGROUND: We wanted to investigate the influence of native-valve infective endocarditis (IE) on long-term outcomes of surgical aortic valve replacement (SAVR). METHODS: Native-valve patients with IE (n = 191) were compared to propensity score-matched patients without IE (n = 191), all treated with SAVR, in a multicentre, population-based cohort register study in Finland. The median follow-up was 6.2 years. RESULTS: Infective endocarditis as the indication for SAVR was associated with an increased hazard of 10-year mortality (37.1% vs 24.2%; HR 1.83; CI 1.03-3.26; P = .039). Ischaemic stroke was also more frequent in IE patients during 10-year follow-up (15.8% vs 7.5%; HR 3.80; CI 1.42-10.18; P = .008). Major bleeding within first year after SAVR was more frequent in patients with IE (7.0% vs 2.9%; P = .038). Ten-year major bleeding rate was 32.4% in IE vs 24.5% in non-IE groups (P = .174). Aortic valve re-operation rate was 4.3% in IE vs 8.4% in non-IE groups (P = .975). Admission duration after SAVR was longer in IE (median 29 vs 9 days; P < .0001). There was no difference in 30-day mortality after SAVR. CONCLUSIONS: Patients with native-valve IE have a higher risk of death, ischaemic stroke, and early major bleeding after SAVR than matched patients without IE. Results confirm the high risk for complications of IE patients after SAVR and highlight the importance of vigorous prevention of both stroke and bleeding after SAVR in these patients.

High-Risk Periods for Adult Traumatic Brain Injuries: A Nationwide Population-Based Study.

INTRODUCTION: There is minimal existing available information on nationwide seasonal peaks in traumatic brain injuries (TBIs). This lack of information is an impediment to the effective development of prevention programs, societal policies, and hinders the resourcing of medical emergency services. Our current aim is to study nationwide population-based high-risk periods TBI over a 15-year study period in Finland. METHODS: Nationwide databases were searched for all admissions with a TBI diagnosis and later for deaths of persons ≥16 years of age during 2004-2018. The search included all hospitals that provide acute TBI care in Finland. RESULTS: The study period included 69,231 TBI-related hospital admissions (men = 62%). We found that for men, the highest rate of TBIs occurred on Saturdays, whereas women experience the highest rate of TBIs on Mondays. The highest rate of TBIs in men occurred in July, while women experienced the highest rate of TBIs in January. TBI-related hospital admissions (incidence risk ratio [IRR] 1.090, 95% CI 1.07-1.11, p < 0.0001) and mortality within 30 days after TBI (hazard ratio [HR] 1.057, 95% CI 1.001-1.116, p = 0.0455) were more common on public holidays and weekends than on weekdays. There was an increasing trend in the proportion of TBI-related hospital admissions occurring on public holidays and weekends from 2004 (31.5%) to 2018 (33.4%) (p = 0.0007). In summer months, TBI-related hospital admissions (IRR 1.10, 95% CI 1.08-1.12, p < 0.0001) and 30-day mortality (HR 1.069, 95% CI 1.010-1.131, p = 0.0211) were more common than in other months. TBIs occurred more often in younger and healthier individuals on these index days and times. In terms of specific public holidays, the TBI risk was overall higher on New Year's Eves and Days (IRR 1.40, 95% CI 1.25-1.58, p < 0.0001) and Midsummer's Eves and Days (IRR 1.36, 95% CI 1.20-1.54, p < 0.0001), compared to nonworking days. This finding was significant in both genders. CONCLUSIONS: TBI-related hospital admissions and mortality were more common on public holidays, weekends, and in summer months in Finland. People who sustained TBIs on these days were on average younger and healthier. The occurrence of TBIs on public holidays and weekends is increasing at an alarming rate.

Sex Differences in Outcomes Following Acute Coronary Syndrome Treated With Coronary Artery Bypass Surgery.

BACKGROUND: A person's sex is suggested to impact their outcome after acute coronary syndrome (ACS) and cardiac surgery, although evidence in controversial. This study examined sex differences in outcomes of ACS patients treated with coronary artery bypass grafting (CABG). METHODS: Patients aged ≥18 year with ACS and treated with first-time isolated CABG in Finland between 2004-2014 were retrospectively identified from a national registry (n=6,683, 24% women). Propensity score matching (1:1) was used to identify 1,607 women and 1,607 men with comparable baseline features (mean age 71 years and follow-up 7.1 years). In-hospital outcomes of all matched patients and long-term (10-year) outcomes of hospital survivors were studied. RESULTS: Women had higher in-hospital mortality (4.5 vs 2.6%; HR, 1.83; 95% CI, 1.18-2.86; p=0.008) but lower long-term all-cause mortality (28.3 vs 34.4%; HR, 0.70; 95% CI, 0.58-0.84; p<0.0001) and cardiovascular mortality (19.5 vs 23.7%; HR, 0.69; 95% CI, 0.55-0.86; p=0.001) as well as long-term major bleeding (11.6 vs 13.6%; HR, 0.69; 95% CI, 0.49-0.97; p=0.032). Re-sternotomy was also less common among women (3.7 vs 5.4%; OR 0.69; CI 0.49-0.96; p=0.029). There were no differences in length of stay (8.8 days in women vs 9.0 days in men) or in the occurrence of a composite major adverse cardiovascular event (MACE) in long-term follow-up (43.0% in women vs 46.5% in men; p=0.800). CONCLUSIONS: Outcomes after CABG-treated ACS differed between sexes. Women had higher in-hospital mortality, while men had higher long-term mortality and occurrence of major bleeding. The long-term risk of combined MACE was comparable between sexes.

Wilson's Disease in Finland: A Nationwide Population-Based Study.

BACKGROUND: Data on the epidemiology and prognosis of Wilson's disease are scarce, and no clinical data are available from Finland. METHODS: All persons diagnosed and treated for Wilson's disease in Finnish hospitals in 1998 to 2017 were identified. Data were collected from national registries and patient charts. RESULTS: The point prevalence was 0.45/100,000 (95% confidence interval, 0.29-0.67) on December 31, 2017, but no more than 0.35/100,000 (95% confidence interval, 0.21-0.55) among native Finns. Annual incidence was 0.016/100,000 (95% confidence interval, 0.0093-0.026). Median age at diagnosis was 15.8 years (interquartile range, 8.3-32.2; range, 3.8-48.1 years). Upon presentation, liver damage was observed in 58%, neurological signs and symptoms (most often tremor and dysarthria) in 40%, and 32% of patients were asymptomatic. Patients had poorer long-term survival (hazard ratio, 2.92 for death; P = 0.005) compared with matched controls. CONCLUSIONS: Wilson's disease is very rare in Finland. Patients have an increased risk of death indicating an unmet treatment need. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Glucagon-like peptide-1 receptor expression after myocardial infarction: Imaging study using 68Ga-NODAGA-exendin-4 positron emission tomography.

BACKGROUND: Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling protects against cardiac dysfunction and remodeling after myocardial infarction (MI). The aim of the study was to evaluate 68Ga-NODAGA-exendin-4 positron emission tomography (PET) for assessment of GLP-1R expression after MI in rats. METHODS AND RESULTS: Rats were studied at 3 days, 1 and 12 weeks after permanent coronary ligation or a sham-operation. Rats were injected with 68Ga-NODAGA-exendin-4 and scanned with PET and contrast-enhanced computed tomography (CT) followed by digital autoradiography and histology of left ventricle tissue sections. 68Ga-NODAGA-exendin-4 PET/CT showed focally increased tracer uptake in the infarcted regions peaking at 3 days and continuing at 1 week after MI. Pre-treatment with an unlabeled exendin-4 peptide significantly reduced 68Ga-NODAGA-exendin-4 uptake. By autoradiography, 68Ga-NODAGA-exendin-4 uptake was 8.6-fold higher in the infarcted region and slightly increased also in the remote, non-infarcted myocardium at 1 week and 12 weeks post-MI compared with sham. Uptake of 68Ga-NODAGA-exendin-4 correlated with the amount of CD68-positive macrophages in the infarcted area and alpha-smooth muscle actin staining in the remote myocardium. CONCLUSIONS: 68Ga-NODAGA-exendin-4 PET detects up-regulation of cardiac GLP-1R expression during healing of MI in rats and may provide information on the activated repair mechanisms after ischemic myocardial injury.

68Ga-DOTA chelate, a novel imaging agent for assessment of myocardial perfusion and infarction detection in a rodent model.

BACKGROUND: Magnetic resonance imaging (MRI) with Gadolinium 1,4,7,10-tetraazacyclododecane-N',N″,N''',N″″-tetraacetic acid (Gd-DOTA) enables assessment of myocardial perfusion during first-pass of the contrast agent, while increased retention can signify areas of myocardial infarction (MI). We studied whether Gallium-68-labeled analog, 68Ga-DOTA, can be used to assess myocardial perfusion on positron emission tomography/computed tomography (PET/CT) in rats, comparing it with 11C-acetate. METHODS: Rats were studied with 11C-acetate and 68Ga-DOTA at 24 hours after permanent ligation of the left coronary artery or sham operation. One-tissue compartmental models were used to estimate myocardial perfusion in normal and infarcted myocardium. After the PET scan, hearts were sectioned for autoradiographic detection of 68Ga-DOTA distribution. RESULTS: 11C-acetate PET showed perfusion defects and histology showed myocardial necrosis in all animals after coronary ligation. Kinetic modeling of 68Ga-DOTA showed significantly higher k1 values in normal myocardium than in infarcted areas. There was a significant correlation (r = 0.82, P = 0.001) between k1 values obtained with 68Ga-DOTA and 11C-acetate. After 10 minutes of tracer distribution, the 68Ga-DOTA concentration was significantly higher in the infarcted than normal myocardium on PET imaging and autoradiography. CONCLUSIONS: Our results indicate that acute MI can be detected as reduced perfusion, as well as increased late retention of 68Ga-DOTA.

Concomitant use of drugs known to cause interactions with oral antiplatelets-polypharmacy in acute coronary syndrome outpatients in Finland.

PURPOSE: Use of oral antiplatelets (OAPs) is essential for preventing thrombotic events in patients with acute coronary syndrome (ACS). Effects of clopidogrel, prasugrel, and ticagrelor may be enhanced due to pharmacodynamic interactions, but as CYP substrates, they are prone to pharmacokinetic interactions too. The aim was to study polypharmacy in ACS patients following hospital discharge. METHODS: This observational drug utilization study linked patient-level data from nationwide registers. The study population consisted of adult ACS patients discharged from Finnish hospitals in 2009-2013. Logistic regression was used to model the probability of drug-drug interactions with odd ratios for predefined predictors such as age, gender, and ACS type. RESULTS: In the cohort of 54,416 ACS patients, 91% of those treated with OAP received clopidogrel. Of clopidogrel-treated patients, 12% purchased warfarin at least once while on clopidogrel treatment. Old age, male sex, ST-elevation myocardial infarction as index event, and a history of previous ACS events were associated with an increased risk of warfarin-OAP interaction (p < 0.001 for all). Ibuprofen, and serotonergic drugs tramadol, citalopram, and escitalopram were the next most common drugs causing pharmacodynamic interactions. In general, concomitant use of drugs known to cause pharmacokinetic interactions was rare, but both esomeprazole and omeprazole were prescribed in more than 6% of clopidogrel-treated patients. CONCLUSIONS: Warfarin and ibuprofen were the most commonly used concomitant medications causing pharmacodynamic interactions and potentially increasing the risk of bleeding in OAP-treated patients. Esomeprazole and omeprazole were used in clopidogrel-treated patients although there are alternatives available for gastric protection.