Bone marrow lesions in knee osteoarthritis assessed by dynamic contrast-enhanced MRI with histopathological correlations.

BACKGROUND: Bone marrow lesions (BMLs) in knee osteoarthritis (OA) have been assessed histopathologically and by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); however, a direct comparison of the results has not been reported. PURPOSE: To evaluate and compare the findings by DCE-MRI and histopathology of subchondral BMLs in knee OA. MATERIAL AND METHODS: In total, 19 patients with medial tibiofemoral knee OA undergoing total knee arthroplasty were analyzed. Preoperative MRI, including a DCE sequence, was performed, and bone biopsies were obtained from the resected specimens corresponding to BML areas. The contrast enhancement by DCE-MRI was analyzed using semi-quantitative (area under the curve [AUC]), peak enhancement [PE]), and quantitative (Ktrans, Kep) methods. Enhancement in the medial OA compartment was compared with similar areas in a normal lateral compartment, and the DCE characteristics of BMLs were correlated with semi-quantitatively graded histopathological features. RESULTS: AUC and PE were significantly higher in medial tibial and femoral BMLs compared with the values in the lateral condyles; Ktrans and Kep were only significantly higher in the tibial plateau. In the tibia, AUC and PE were significantly correlated with the grade of vascular proliferation, and PE also with the degree of marrow fibrosis. There was no significant correlation between AUC/PE and histopathological findings in the femur and no correlation between quantitative DCE parameters and histopathological findings. CONCLUSION: BML characteristics by semi-quantitative DCE in the form of AUC and PE may be used as parameters for the degree of histopathological vascularization in the bone marrow whereas quantitative DCE data were less conclusive.

Enhanced autopsy triage (EA-Triage) in drug-related deaths: integrating quick toxicological analysis and postmortem computed tomography.

The objective was to assess the diagnostic accuracy of an enhanced autopsy triage (EA-Triage) setup consisting of postmortem computed tomography (PMCT), simulated quick toxicological analysis (sQTA), external examination, and case information in determining cause of death (COD) in persons with past or current use of illegal drugs (drug-related deaths). Information on drug-related deaths selected for medico-legal autopsy in 2020-2021 at the Department of Forensic Medicine, Aarhus University, Denmark, was analyzed retrospectively. The included cases underwent conventional autopsy, PMCT, and systematic toxicological analysis. A board-certified forensic pathologist, who was blinded to the internal examination and COD from the medico-legal autopsy, determined COD based on the EA-Triage setup. 154 cases with a median age of 40.6 years (range 17-70 years, 82% males) were included. The COD determined by medico-legal autopsy and that determined by EA-Triage matched in 113 cases (73%), including those with an unknown COD. EA-Triage and medico-legal autopsy determined unknown COD in 45 (29%) and 5 cases (3%), respectively. Excluding cases with an unknown COD, EA-Triage predicted COD in 109 cases (71%); of those, 72 (66%) had no unexplained case circumstances or suspicion of a criminal act. In these 72 cases, the CODs determined by EA-Triage and medico-legal autopsy matched in 71 cases (99%), and the sensitivity and specificity for detecting lethal intoxication were 100% and 90%, respectively. EA-Triage showed strong diagnostic accuracy for determining COD in drug-related deaths. This method may be suitable for enhancing preautopsy triage and guiding police investigations at an early stage.

Comment on: "Bone marrow embolism: should it result from traumatic bone lesions? a histopathological human autopsy study".

Farid et al., described how 8 of 11 cases of Bone Marrow Embolism were found to be non-traumatic. In our research group we found several shortcomings in the methodology, and within our own Institute we could not replicate the results.

Histomorphometric case-control study of subarticular osteophytes in patients with osteoarthritis of the hip.

OBJECTIVE: The objective of this cross-sectional case-control study was to determine the prevalence and size of marginal and subarticular osteophytes in patients with osteoarthritis (OA), and to compare these to that of a control group. DESIGN: We investigated femoral heads from 25 patients with OA following hip replacement surgery, and 25 femoral heads from a control group obtained post-mortem. The area and boundary length of the femoral head, marginal osteophytes, and subarticular osteophytes were determined with histomorphometry. Marginal osteophytes were defined histologically as bony projections at the peripheral margin of the femoral head, while subarticular osteophytes were defined as areas of bone that expanded from the normal curvature of the femoral head into the articular cartilage. RESULTS: The prevalence of OA patients with marginal- and subarticular osteophytes were 100 and 84%, respectively. Whereas the prevalence of the participants in the control group with marginal- and subarticular osteophytes were 56 and 28%, respectively. The area and boundary length of marginal osteophytes was (median (Interquartile range)) 165.3mm2 (121.4-254.0) mm2 and 75.1 mm (50.8-99.3) mm for patients with OA compared to 0 mm2 (0-0.5) mm2 and 0 mm (0-0.5) mm for the control group (P <  0.001). For the subarticular osteophytes, the area and boundary length was 1.0 mm2 (0-4.4) mm2 and 1.4 mm (0-6.5) mm for patients with OA compared to 0 mm2 (0-0.5) mm2 and 0 mm (0-0.5) mm for the control group (P <  0.001). CONCLUSION: As expected, both marginal- and subarticular osteophytes at the femoral head, were more frequent and larger in patients with OA than in the control group. However, in the control group, subarticular osteophytes were more prevalent than expected from the minor osteophytic changes at the femoral head margin, which may suggest that subarticular osteophytes are an early degenerative phenomenon that ultimately might develop into clinical osteoarthritis.

CT-guided transarticular biopsy of the sacroiliac joint: Technique and histomorphological results. A preliminary study.

OBJECTIVE: To introduce and evaluate computed tomography (CT)-guided transarticular needle biopsy of the cartilaginous sacroiliac joint (SIJ) and to assess the biopsy results microscopically. MATERIALS AND METHODS: The new CT-guided transarticular biopsy of the SIJ was performed in a young corpse and ten patients, two males and eight females aged 18-81 years. All patients had abnormal findings by magnetic resonance imaging (MRI) of the SIJs, including bone marrow edema, related to different types of joint disorders. The biopsies were focused on areas with bone marrow edema. The quality of the specimens obtained, using two different types of biopsy needles, was assessed microscopically. RESULTS: Biopsies containing cartilage, subchondral plate, and bone marrow from the iliac and sacral sides were obtained from the corpse and three patients and from the iliac bone only in two patients. In three patients, the biopsy needles could not penetrate the bone marrow to the joint facet due to pronounced subchondral sclerosis, but adequate marrow biopsies were obtained. Two biopsies were inadequate, one due to technical problems and one was crushed during preparation. Histological assessment of eight adequate specimens revealed inflammatory bone marrow changes, except in two specimens from females with pronounced sclerosis conforming to osteitis condensans ilii. CONCLUSIONS: Transarticular SIJ biopsies are obtainable and can be directed towards areas with MRI abnormalities. They can be used to confirm inflammatory changes histologically. With the biopsy needles used, severe bone marrow sclerosis may hinder penetration to the cartilage, but bone marrow specimens can be obtained.

Joint European Society of Paediatric Radiology (ESPR) and International Society for Forensic Radiology and Imaging (ISFRI) guidelines: paediatric postmortem computed tomography imaging protocol.

Postmortem CT for investigating childhood deaths is increasingly utilised as a noninvasive adjunct or alternative to standard autopsy; however there are no standardised published imaging protocols. This article describes a standardised imaging protocol that has been developed based on current practices of international postmortem imaging practitioners and experts. This recommendation is expected to be useful for postmortem imaging centres wishing to update their existing practices and for those starting paediatric postmortem CT as a new service.

Fatal subarachnoid hemorrhage associated with internal carotid artery dissection resulting from whiplash trauma.

Spinal injury following inertial loading of the head and neck (whiplash) is a common sequel of low speed traffic crashes. A variety of non-musculoskeletal injuries have been described in association with injury to the spine following whiplash trauma, including traumatic brain injury, vestibular derangement, and cranial nerve injury, among others. Vascular injuries in the head and neck have, however, only rarely been described. We present the case of a middle-aged male who sustained an ultimately fatal injury that resulted from injury to the internal carotid artery (ICA) and intracerebral vascular structures following a hard braking maneuver, with no direct head- or neck contact with the vehicular interior. Based on this unusual mechanism of injury we reviewed hospital data from the United States nationwide inpatient database (NIS) to assess the frequency of similar injuries reportedly resulting from traffic crashes. The post-mortem examination revealed a left internal carotid artery dissection associated with subarachnoid hemorrhage (SAH). Based on the close temporal association, the absent prior history, and the plausibility of the injury mechanism, the injury was attributed to the braking maneuver. An analysis of NIS data demonstrated that the prevalence of subarachnoid hemorrhage is significantly higher when there is a traumatic etiology, and higher yet when the trauma is a traffic crash (odds ratio 3.3 and 4.3, respectively). The presented case, together with the hospital inpatient data analysis, indicate that although SAH in combination with ICA dissection is relatively rare, it is substantially more probable following a traffic crash. In a clinical or forensic setting the inference that magnitude of a trauma was low should not serve as a basis for either excluding a cervical artery dissection from a differential diagnosis, or for excluding the trauma as a cause of a diagnosed dissection. This case report illustrates a rare fatal outcome of inertial load to the head and neck induced by a sudden braking event in a commonly experienced non-collision traffic incident. The likely mechanism of injury resulted from interaction between the occupant and the 3-point seat belt. These findings indicate that ICA dissections are substantially more likely to be associated with SAH following head and neck trauma, regardless of the magnitude of the traumatic event or whether an impact was involved.

Investigation of a fatal airplane crash: autopsy, computed tomography, and injury pattern analysis used to determine who was steering the plane at the time of the accident. A case report.

A fatal accident is reported in which a small single-engine light airplane crashed. The airplane carried two persons in the front seats, both of whom possessed valid pilot certificates. Both victims were subject to autopsy, including post-mortem computed tomography scanning (PMCT) prior to the autopsy. The autopsies showed massive destruction to the bodies of the two victims but did not identify any signs of acute or chronic medical conditions that could explain loss of control of the airplane. PMCT, histological examination, and forensic chemical analysis also failed to identify an explanation for the crash. A detailed review of an airplane identical to the crashed airplane was performed in collaboration with the Danish Accident Investigation Board and the Danish National Police, National Centre of Forensic Services. The injuries were described using the abbreviated injury scale, the injury severity score, 3-dimensional reconstructions of the PMCT, and an injury pattern analysis. We describe how, on basis of these data, we reached a conclusion about which of the two victims was the most likely to have been in control of the airplane at the time of accident. Furthermore, we argue that all victims of fatal airplane crashes should be subject to forensic autopsy, including PMCT and forensic chemical analysis. The continuous accumulation of knowledge about injury patterns from "simple" accidents is the foundation for the correct analysis of "difficult" accidents.

Increased risk of fatal intoxication and polypharmacy among psychiatric patients at death.

Patients suffering from psychiatric disorders have an excess mortality and a shorter life span expectancy compared to the general population. Furthermore, they are treated with multiple drugs and are known to have an increased risk of drug abuse. In this study, we aimed at investigating the pharmaceutical drug and drug of abuse profiles of the deceased included in the Danish prospective autopsy-based forensic study on psychiatric patients, SURVIVE. Using the postmortem systematic toxicological analysis results, we identified 129 different consumed compounds in our population (n = 443). Polypharmacy (≥5 compounds) was detected in 39.5% of the deceased. Deceased with a psychiatric diagnosis or who died from a fatal intoxication had significantly more compounds at the time of their death compared to having either no psychiatric diagnosis or another cause of death, respectively. Evidence of drug abuse was present, as 29.8% of our total population had consumed either methadone or illicit drugs of abuse, excluding tetrahydrocannabinol. Of those deceased with a psychiatric diagnosis, 33.6% had either consumed methadone or illicit drugs of abuse, a greater number than those without a psychiatric diagnosis. Fatal intoxication was the most frequent cause of death (40.6%) with methadone as the major intoxicant. Here, we found that those without a psychiatric diagnosis had fewer fatal pharmaceutical drug intoxications compared to the psychiatric diagnosis groups. Our findings add further context to understanding the excess mortality of psychiatric patents, since there is an increased occurrence of fatal intoxication, polypharmacy, and drug abuse in this population.

Calcified cartilage in patients with osteoarthritis of the hip compared to that of healthy subjects. A design-based histological study.

OBJECTIVE: Calcified cartilage is suggested to be involved in the pathogenesis of osteoarthritis (OA) by facilitating endochondral ossification at the bone-cartilage unit. Therefore, the objective was to quantify the volume and surface area of the calcified cartilage in the femoral head in OA patients and healthy subjects. MATERIALS AND METHODS: We used design-based stereological principles, i.e., systematic uniform random sampling and vertical uniform random sections of the entire femoral head. We investigated the articular and calcified cartilage and femoral head surface area and volume, excluding fovea capitis and marginal osteophytes, in 20 patients with OA and 15 healthy subjects. RESULTS: The volume of the calcified cartilage was significantly larger for the patients with OA compared with the healthy subjects (mean difference [95% CI]) (284 [110,457] mm3, p = 0.002). The upper and lower surface area of the calcified cartilage, i.e. the tidemark and cement line, were both significantly larger for OA patients compared with the healthy subjects (17.8 [8.4,27.3] cm2, p < 0.001) and (38.7 [20.8,56.7] cm2, p = 0.002), respectively. The volume of the calcified cartilage and the volume of the femoral head were significantly correlated for the patients with OA (Spearman's ρ = 0.51, p = 0.021), but not for the healthy subjects (ρ = 0.41, p = 0.123). CONCLUSIONS: Patients with OA had a larger femoral head surface area and more calcified cartilage compared to healthy subjects. The volume of the calcified cartilage correlated positively with the volume of the femoral head for patients with OA, but not for healthy subjects. This strongly supports the existing view that bone growth in OA is associated with endochondral ossification.

Age-related histological changes in calcified cartilage and subchondral bone in femoral heads from healthy humans.

OBJECTIVE: Age is the most important risk factor for osteoarthritis (OA). It is suggested that changes in subchondral bone and calcified cartilage may occur in early OA. Therefore, the aim was to investigate age-related changes in the femoral head composition. We hypothesise that the thickness of the subchondral bone plate decreases with age, while the thickness of the calcified cartilage increases with age as seen in early-stage OA. METHODS: Femoral heads from 29 women (20-74 years) and 32 men (23-78 years), who had died suddenly and unexpectedly, were obtained at autopsy. Individuals with bone or joint diseases or macroscopic abnormal cartilage were excluded. Using design-based stereology, femoral head volume as well as thickness and volume of the calcified cartilage and subchondral bone plate were estimated and correlated to sex and age. RESULTS: The thickness and volume of the subchondral bone plate were not correlated with age. Calcified cartilage thickness and volume correlated positively with age in women, while the femoral head volume was correlated positively with age in men. CONCLUSION: In human femoral heads obtained from a cross-sectional population without macroscopic OA changes, the thickness of the subchondral bone plate did not change with age, which differs from the thinning seen in early OA. Surprisingly, the age-related changes of the volume and thickness of the calcified cartilage and of the volume of the femoral head were different for women and men. This indicate that cartilage and bone metabolism is sex-specific, which may influence ageing of the hip joint.

Thickness of the bone-cartilage unit in relation to osteoarthritis severity in the human hip joint.

OBJECTIVE: Bone formation is a hallmark of osteoarthritis (OA). It has been speculated that bone formation may occur because of ossification at the bone-cartilage unit, that is, bone formation directly involving the calcified cartilage (CC). This study aimed to investigate the thickness of the CC and subchondral bone (SCB) in relation to the severity of the overlying articular cartilage (AC) degeneration. DESIGN: We investigated femoral heads from 20 patients with OA and 15 healthy subjects with design-based stereology using systematic uniform random sampling of the entire joint surface. This was combined with the Osteoarthritis Research Society International (OARSI) OA cartilage histopathology assessment system, thus obtaining focal OARSI grades paired with thickness measurements of AC, CC and the SCB. RESULTS: The patients with OA had thicker CC (mean 159; 95% CI 144 to 177 µm) compared with the healthy subjects (mean 132; 95% CI 113 to 1550 µm; p=0.036), and this difference was even higher in areas without loss of AC thickness (OARSI grade ≤3); 187 (95% CI 164 to 214) µm vs 132 (95% CI 113 to 155) µm (p=0.001). In the patients with OA, a thicker SCB was observed in areas with loss of AC thickness (OARSI grade ≥4), but not in areas without loss of AC thickness (OARSI grade ≤3). CONCLUSION: The study showed that thicker CC is present in early stages of OA, suggesting that bone formation by endochondral ossification is an early phenomenon of OA. Thickening of the SCB was present, but only in areas with denuded bone. Suggesting that also appositional bone growth occurs and that it may be a consequence of changed biomechanics.

Diffusion tensor imaging of peripheral nerves in non-fixed post-mortem subjects.

PURPOSE: While standard magnetic resonance imaging (MRI) sequences are increasingly employed in post-mortem (PM) examinations, more advanced techniques such as diffusion tensor imaging (DTI) remain unexplored in forensic sciences. Therefore, we studied the temporal stability and reproducibility of DTI and fiber tractography (FT) in non-fixed PM subjects. In addition, we investigated the lumbosacral nerves with PMDTI and compared their tissue characteristics to in vivo findings. METHODS: MRI data were acquired on a 1.5T MRI scanner in seven PM subjects, consisting of six non-trauma deaths and one chronic trauma death, and in six living subjects. Inter-scan (within one session) and inter-session (between days) reproducibility of diffusion parameters, fractional anisotropy (FA), and mean diffusivity (MD), were evaluated for the lumbosacral nerves using Bland-Altman and Jones plots. Diffusion parameters in nerves L3-S2 were compared to living subjects using the non-parametric Mann-Whitney U test. RESULTS: Reproducibility of diffusion values of inter-scan 95% limits of agreement ranged from -0.058 to 0.062 for FA, and (-0.037 to 0.052)×10(-3)mm(2)/s for MD. For the inter-session this was -0.0423 to 0.0423, and (-0.0442 to 0.0442)×10(-3)mm(2)/s for FA, and MD, respectively. Although PM subjects showed approximately four-fold lower diffusivity values compared to living subjects, FT results were comparable. The chronic trauma case showed disorganization and asymmetry of the nerves. CONCLUSION: We demonstrated that DTI was reproducible in characterizing nervous tissue properties and FT in reconstructing the architecture of lumbosacral nerves in PM subjects. We showed differences in diffusion values between PM and in vivo and showed the ability of PMDTI and FT to reconstruct nerve lesions in a chronic trauma case. We expect that PMDTI and FT may become valuable in identification and documentation of PM nerve trauma or pathologies in forensic sciences.

Coding ill-defined and unknown cause of death is 13 times more frequent in Denmark than in Finland.

Exact cause and manner of death determination improves legislative safety for the individual and for society and guides aspects of national public health. In the International Classification of Diseases, codes R00-R99 are used for "symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified" designated as "ill-defined" or "with unknown etiology". The World Health Organisation recommends avoiding the use of ill-defined and unknown causes of death in the death certificate as this terminology does not give any information concerning the possible conditions that led to the death. Thus, the aim of the study was, firstly, to analyse the frequencies of R00-R99-coded deaths in mortality statistics in Finland and in Denmark and, secondly, to compare these and the methods used to investigate the cause of death. To do so, we extracted a random 90% sample of the Finnish death certificates and 100% of the Danish certificates from the national mortality registries for 2000, 2005 and 2010. Subsequently, we analysed the frequencies of forensic and medical autopsies and external clinical examinations of the bodies in R00-R99-coded deaths. The use of R00-R99 codes was significantly higher in Denmark than in Finland; OR 18.6 (95% CI 15.3-22.4; p<0.001) for 2000, OR 9.5 (95% CI 8.0-11.3; p<0.001) for 2005 and OR 13.2 (95% CI 11.1-15.7; p<0.001) for 2010. More than 80% of Danish deaths with R00-R99 codes were over 70 years of age at the time of death. Forensic autopsy was performed in 88.3% of Finnish R00-R99-coded deaths, whereas only 3.5% of Danish R00-R99-coded deaths were investigated with forensic or medical autopsy. The codes that were most used in both countries were R96-R99, meaning "unknown cause of death". In Finland, all of these deaths were investigated with a forensic autopsy. Our study suggests that if all deaths in all age groups with unclear cause of death were systematically investigated with a forensic autopsy, only 2-3/1000 deaths per year would be coded as an ill-defined and unknown cause of death in national mortality statistics. At the same time the risk to overlook unnatural deaths is decreased to a minimum. To achieve this in Denmark requires that the existing legislation on cause of death investigation would need to be changed to ensure that all deaths with unknown cause of death are investigated with a forensic autopsy.

Autopsy rate in suicide is low among elderly in Denmark compared with Finland.

National differences in the legislation on cause and manner of death investigation are reflected in a high autopsy rate in suicides in Finland and a low corresponding rate in Denmark. The consequences for mortality statistics of these different investigation practices on deaths classified as suicides in Denmark and Finland, respectively, are not known in detail. The aim of this article was to analyse autopsy rates in deaths classified as suicides, and to identify any differences in investigation practices in deaths with a comparable cause of death, but classified as unnatural deaths other than suicide. Data from the mortality registries were summarised for the years 2000, 2005 and 2010. Autopsy rates (total, forensic and medical) were analysed with regard to deaths classified as suicide, and they were compared for three age groups (1-50 years, 51-70 years and ≥71 years) and for causes of death. Deaths classified as suicide were compared with other unnatural classifications, and comparable causes of death were coded into six subgroups: poisonings, suffocations/strangulations, firearm discharges, drowning/submersions, explosions/flames and other/unspecified causes. The total autopsy rate for suicides was 99.8% in Finland and 13.2% in Denmark. Almost all of these autopsies were conducted as forensic autopsies. In the age group ≥71 years, Danish suicides outnumbered Finnish suicides (410 versus 283). The total autopsy rate was lower in the more senior age group in Denmark (19.5%, 9.9%, 5.6%), whereas it was consistently high in Finland (99.8%, 99.9%, 99.6%). Among Danish deaths due to poisonings, the autopsy rate was 89.5% when these were classified as accidents, but only 20.7% for cases classified as suicides. The number of deaths in the two Danish subgroups was comparable (550 versus 553). In Denmark, the decision regarding the need, if any, for a forensic autopsy is made during the external forensic examination of the body. Our study showed that the limited use of forensic autopsy to confirm the cause of death in deaths classified as suicides raises doubts about the accuracy of the Danish suicide mortality statistics. Our finding is emphasised by those cases in which the cause of death was registered as intentional self-poisoning. The high number of suicides among the elderly in Denmark is striking and begs further investigation and research. Overall, our data from Finland and Denmark reveal striking differences between the two countries and warrant further comparative studies on the subject in other countries.

Cost-consequence analysis of cause of death investigation in Finland and in Denmark.

The 1990s 12-16% total autopsy rate in Denmark has until now declined to 4%, while in Finland, it has remained between 25 and 30%. The decision to proceed with a forensic autopsy is based on national legislation, but it can be assumed that the financing of autopsies influences the decision process. Only little is known about the possible differences between health economics of Finnish and Danish cause of death investigation systems. The aims of this article were to analyse costs and consequences of Finnish and Danish cause of death investigations, and to develop an alternative autopsy practice in Denmark with another cost profile. Data on cause of death investigation systems and costs were derived from Departments of Forensic Medicine, Departments of Pathology, and the National Police. Finnish and Danish autopsy rates were calculated in unnatural (accident, suicide, homicide and undetermined intent) and natural (disease) deaths, and used to develop an alternative autopsy practice in Denmark. Consequences for society were analysed. The estimated unit cost (€) for one forensic autopsy is 3.2 times lower in Finland than in Denmark (€1400 versus €4420), but in Finland the salaries for forensic pathologists working at the National Institute for Health and Welfare are not included in the unit cost. The unit cost for one medical autopsy is also lower in Finland than in Denmark; €700 versus €1070. In our alternative practice in Denmark, the forensic autopsy rate was increased from 2.2% to 8.5%, and the medical autopsy rate from 2.4% to 5.8%. Costs per 10,000 deaths were estimated to be 50% (±25%) higher than now; i.e. €3,678,724 (2,759,112-4,598,336), but would result in a lower unit cost for forensic autopsies €3,094 (2,320-3,868) and for medical autopsies €749 (562-936). This practice would produce a higher accuracy of national mortality statistics, which, consequently, would entail higher quality in public health, an accurate basis for decision-making in health politics, and better legislative safety in society. The implementation of this alternative practice in Denmark requires that legislation demands that forensic autopsy be performed if causality between unnatural death and cause of death cannot be clarified or if cause of death remains unknown. The Danish Health and Medicines Authority should provide guidelines that request a medical autopsy in natural deaths where more information about disease as a cause of death is needed. Our study results warrant similar health economic analyses of different cause of death investigations in other countries.