The most difficult at-fault fatal crashes to avoid with current active safety technology

Objective We studied which current fatal at-fault crashes would occur despite the most advanced current active safety devices (up to SAE level 2 of driving automation) and how frequent these crashes would be. Methods We carried out a cross-sectional study of passenger cars that were first registered during the period 1st January 2010 to 31st December 2017 in Finland. To gain the true exposure for these cars, we accessed the national Vehicular and Driver Data Register to obtain the mileage information and the registration count for the study period of 2010-17. Similarly, we accessed the registry of Finnish road accident investigation teams and included all fatal at-fault crashes among the cars in our study for the same period. We used a real world reference technology for each active safety system in our analysis and chose one car brand as an example. This gave us exact system specifications and enabled testing the operation of the systems on the road. We performed field tests to gain further information on the precise operation of the safety systems in different operating conditions. Finally, we gathered all information on the studied active safety systems and analyzed the investigated at-fault fatal crashes case-by-case using our four level method. Results Cars in our study were the primary party in 113 investigated fatal accidents during the years 2010-17. In 87 of the accidents, the leading cause of death was the injuries due to the crash, and these cases were classified as “unavoidable” (n = 58, 67 %), “avoidable” (n = 26, 30 %) or unsolved (n = 3, 3 %). Of the 58 “unavoidable” crashes 21 (36 %) were suicides, 21 (36%) involved active driver input which would have prevented the safety system operation, 15 (17 %) featured circumstances beyond the safety system performance and in one loss-of-control crash the driver had disabled the relevant safety system (electronic stability control). The registration years of the cars in our study (2010-17) totaled 3,772,864 and during this period, the cars travelled 75.9 billion kilometers. The crash incidence of the “unavoidable” at-fault fatal crashes was 0.76-0.80 fatal crashes per billion kilometers and 15-16 fatal crashes per million registration years. Conclusions We calculated a crash incidence for the “unavoidable” crashes which was 20–27% smaller than the observed crash rate of ESC-fitted passenger cars in our previous study. We concluded that suicides, active driver input until the crash, and challenging weather and road conditions are the most difficult factors for current active safety systems. Our analysis did not account for issues such as system usability or driver acceptance and therefore our results should be regarded as something that is currently theoretically achievable. However, the observed incidence is a good reference for automated driving development and the crash rate of automated cars.Peer reviewe

Bisphosphonate treatment in children with acute lymphoblastic leukemia and osteonecrosis - radiological and clinical findings in a national cohort

Background: Osteonecrosis (ON) is a recognized complication of childhood ALL, but its optimal management remains unestablished. This study evaluated the effect of bisphosphonate (BP) treatment on the evolution of ON lesions in childhood ALL. Material and Methods: We included a national cohort of ALL patients diagnosed with symptomatic ON before 18 years of age and treated with BPs (N = 10; five males). Patients were followed both clinically and with serial MRIs. ON lesions were graded according to the Niinimaki classification. Results: The 10 patients had a total of 55 ON lesions. The median age was 13.3 years at ALL diagnosis and 14.8 years at ON diagnosis. Four patients had received HSCT before the ON diagnosis. BPs used were pamidronate (N = 7), alendronate (N = 2) and ibandronate (N = 1). The duration of BP treatment varied between 4 months and 4 years. In 4/10 patients, BP treatment was given during the chemotherapy. BPs were well-tolerated, with no severe complications or changes in kidney function. At the end of follow up 13/55 (24%) ON lesions were completely healed both clinically and radiographically; all these lesions were originally graded 3 or less. In contrast, ON lesions originally classified as grade 5 (joint destruction; N = 4) remained at grade 5. All grade 5 hip joint lesions needed surgical treatment. During BP treatment, the pain was relieved in 7/10 patients. At the end of follow-up, none of the patients reported severe or frequent pain. Conclusion: BP treatment was safe and seemed effective in relieving ON-induced pain in childhood ALL. After articular collapse (grade 5) lesions did not improve with BP treatment. Randomized controlled studies are needed to further elucidate the role of BPs in childhood ALL-associated ON.Peer reviewe

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction : The randomized, double-blind, placebo-controlled OXI pilot trial

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to in-terruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocar-dial infarction. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland: A real-world evidence multicenter study

Background: Radium-233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium-223 compared to best supportive care in castration-resistant prostate cancer (CRPC) with bone metastases. However, real-world data are also needed with wider inclusion criteria.Methods: We report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium-223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium-223 in Finland in 2014-2019.Results: The median overall survival (OS) was 13.8 months (range 0.5-57 months), and the median real-world progression-free survival (rwPFS) was 4.9 months (range 0.5-29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium-223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p Conclusion: Radium-223 was well tolerated in routine clinical practice, and most patients achieved pain relief. Pain relief, ALP normalization, lower baseline PSA, and PSA decrease during radium-223 treatment were prognostic for better survival. The efficacy of radium-223 in mCRPC as estimated using OS was comparable to earlier randomized trial in this retrospective real-world study. Our results support using radium-223 for mCRPC patients with symptomatic bone metastases even in the era of new-generation androgen receptor-targeted agents.</p

Health-related Quality of Life of Breast Cancer Survivors Attending an Exercise Intervention Study: A Five-year Follow-up

Background/Aim: As the number of breast cancer survivors is increasing, their long-term health-related quality of life (HRQoL) has become an important issue. The aim of the study is to follow up the HRQoL of breast cancer survivors (BCS) in a prospective randomized exercise intervention study and to compare HRQoL to that of the age-matched general female population. Patients and Methods: Following adjuvant treatment, 537 patients aged 35-68 and capable of exercise training were randomized to a 12-month exercise trial. In 182 of those patients, HRQoL was measured by the generic 15D at baseline and followed up for five years. Furthermore, the HRQoL of all BCS answering the 15D at five-year follow-up (n=390) was compared to that of a representative sample of the general population. Results: After five years, the BCS' mean HRQoL demonstrated a statistically and clinically significant impairment compared to that of the general population (difference -0.023, p<0.001). The mean HRQoL of BCS followed up from baseline until five years did not improve significantly (change=0.007, p=0.27), whereas the dimensions of usual activities (0.043, p=0.004), depression (0.038, p=0.007), distress (0.030, p=0.036), and sexual activity (0.057, p=0.009) did. Conclusion: The HRQoL of BCS was still impaired five years following treatment

Long-term health-related quality of life of breast cancer survivors remains impaired compared to the age-matched general population especially in young women Results from the prospective controlled BREX exercise study

AbstractObjectiveTo investigate long-term health-related quality of life (HRQoL) changes over time in younger compared to older disease-free breast cancer survivors who participated in a prospective randomized exercise trial.MethodsSurvivors (aged 35–68 years) were randomized to a 12-month exercise trial after adjuvant treatment and followed up for ten years. HRQoL was assessed with the generic 15D instrument during follow-up and the younger (baseline age ≤ 50) and older (age >50) survivors’ HRQoL was compared to that of the age-matched general female population (n = 892). The analysis included 342 survivors.ResultsThe decline of HRQoL compared to the population was steeper and recovery slower in the younger survivors (p for interaction ConclusionsHRQoL developed differently in younger and older survivors both regarding the most affected dimensions of HRQoL and the timing of the changes during follow-up. HRQoL of both age groups remained below the population level even ten years after treatment.</p

Objectively assessed disease activity and drug persistence during ustekinumab treatment in a nationwide real-world Crohn's disease cohort

ObjectiveLong-term evidence on ustekinumab treatment response and persistence in patients with Crohn's disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn's disease patients treated with ustekinumab.MethodsThe study was conducted in 17 Finnish hospitals and included adult Crohn's disease patients who received an initial intravenous dose of ustekinumab during 2017-2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records.ResultsThe study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn's disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with >= 1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn's disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P ConclusionsUstekinumab treatment in patients with highly refractory Crohn's disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.</div

Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients

Background Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. Methods A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of 655/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness ("EDS") and nocturnal sleep problems other than OSA (labelled as "insomnia"): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/noninsomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. Results The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/ insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0\ub125.5/h vs. 27.9\ub122.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188-1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity. Conclusions Phenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS

Manifestations and Outcome of Cardiac Sarcoidosis and Idiopathic Giant Cell Myocarditis by 25-Year Nationwide Cohorts

Background Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) share many histopathologic and clinical features. Whether they are parts of a one-disease continuum has been discussed.Methods and Results We compared medical record data of 351 CS and 28 GCM cases diagnosed in Finland since the late 1980s and followed until February 2018 for a composite end point of cardiac death, aborted sudden death, and heart transplantation. Heart failure was the presenting manifestation in 50% versus 15% (PP=0.044), of GCM and CS, respectively. At presentation, left ventricular ejection fraction was P=0.004). The median (interquartile range) of plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) was 5273 (2782-11309) ng/L on admission in GCM versus 859 (290-1950) ng/L in CS (PPPConclusions GCM differs from CS in presenting with more extensive myocardial injury and having worse long-term outcome. Yet the key determinant of prognosis appears to be the extent of myocardial injury rather than the histopathologic diagnosis.</p

Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear