To become part of the team-patient experiences of participating in decision-making for a new treatment (proton beam therapy).

PURPOSE: The aim of this study was to explore patients' experience of participation in the treatment decision of proton beam therapy versus conventional radiotherapy. BACKGROUND: Proton beam therapy (PBT) has become a treatment option for some cancer patients receiving radiotherapy. The decision to give PBT instead of conventional radiotherapy (CRT) needs to be carefully planned together with the patient to ensure that the degree of participation is based on individuals' preferences. There is a knowledge gap of successful approaches to support patients' participation in the decision-making process, which is particularly important when it comes to the situation of having to choose between two treatment options such as PBT and CRT, with similar expected outcomes. METHOD: We conducted a secondary analysis of qualitative data collected from interviews with patients who received PBT for their brain tumor. Transcribed verbatims from interviews with 22 patients were analyzed regarding experiences of participation in the decision-making process leading to PBT. FINDINGS: Participants experienced their participation in the decision-making process to a varying degree, and with individual preferences. Four themes emerged from data: to be a voice that matters, to get control over what will happen, being in the hand of doctors' choice, and feeling selected for treatment. CONCLUSION: A decision for treatment with PBT can be experienced as a privilege but can also cause stress as it might entail practical issues affecting everyday life in a considerable way. For the patient to have confidence in the decision-making process, patients' preferences, expectations, and experiences must be included by the healthcare team. Including the patient in the healthcare team as an equal partner by confirming the person enables and facilitates for patients' voice to be heard and reckoned with. Person-centered care building on a partnership between patients and healthcare professionals should provide the right basis for the decision-making process.

Evaluating patient reported outcomes and experiences in a novel proton beam clinic - challenges, activities, and outcomes of the ProtonCare project.

BACKGROUND: The ProtonCare Study Group (PCSG) was formed with the purpose to develop and implement a framework for evaluation of proton beam therapy (PBT) and the related care at a novel clinic (Skandionkliniken), based on patient reported data. METHOD: A logic model framework was used to describe the process of development and implementation of a structured plan for evaluation of PBT for all diagnoses based on patient reported data. After the mission for the project was determined, meetings with networks and stakeholders were facilitated by PCSG to identify assumptions, resources, challenges, activities, outputs, outcomes, and outcome indicators. RESULT: This paper presents the challenges and accomplishments PCSG made so far. We describe required resources, activities, and accomplished results. The long-term outcomes that were outlined as a result of the process are two; 1) Improved knowledge about health outcomes of patients that are considered for PBT and 2) The findings will serve as a base for clinical decisions when patients are referred for PBT. CONCLUSION: Using the logical model framework proved useful in planning and managing the ProtonCare project. As a result, the work of PCSG has so far resulted in long-lasting outcomes that creates a base for future evaluation of patients' perspective in radiotherapy treatment in general and in PBT especially. Our experiences can be useful for other research groups facing similar challenges. Continuing research on patients´ perspective is a central part in ongoing and future research. Collaboration, cooperation, and coordination between research groups/networks from different disciplines are a significant part of the work aiming to determine the more precise role of PBT in future treatment options.

Postmortem genetic testing of the ryanodine receptor 2 (RYR2) gene in a cohort of sudden unexplained death cases.

The aim of this investigation was to identify pathogenic variants of the ryanodine receptor 2 (RYR2) gene in a cohort of persons aged 0-40 years who died of sudden unexpected death syndrome (SUD), including a cohort of infants who died of sudden infant death syndrome (SIDS). We genetically screened 29 of the 105 exons of the RYR2 gene associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) in 74 cases of SUD without reported structural abnormalities of the heart. Cases were selected from the case database at the Institute of Forensic Medicine, and subsequent mutational screening by DNA sequencing was performed to detect variants in DNA samples extracted from blood samples of deceased persons. A total of 7 of the examined 74 cases were heterozygous for a rare sequence variant in the RYR2 gene. We identified five novel missense variants (p.Q486H, p.D1872N, p.G2367R, p.E4213D, and p.H4579Y), one synonymous variant (p.L4767L), and one previously reported missense variant (p.G4315E). Follow-up studies were possible in family members of three probands (p.Q486H, p.D1872N, and p.H4579Y), and clinical examinations were conducted in family members of two of these probands (p.Q486H and p.H4579Y). In conclusion, we identified a higher prevalence of variants in the CPVT-associated gene RYR2 than in a previously reported cohort of SIDS (9.4% vs. 1-2%). Segregation studies show that one variant (p.H4579Y) co-segregates with CPVT and is presumed to be pathogenic.

Re-irradiation in Paediatric Tumours of the Central Nervous System: National Guidelines from the Swedish Workgroup of Paediatric Radiotherapy.

There is a lack of clinical protocols for re-irradiation in paediatric central nervous system (CNS) tumours. To fill this void, the Swedish Workgroup of Paediatric Radiotherapy (SBRTG) compiled national guidelines on re-irradiation in paediatric CNS tumours (diffuse intrinsic pontine glioma, ependymoma, germinoma and medulloblastoma). These have been in clinical practice since 2019 in all paediatric radiotherapy centres in Sweden. Since the implementation, the guidelines have been complemented with a yearly review on clinical outcome and toxicities in all paediatric patients treated according to the guidelines. This article presents the Swedish national guidelines on re-irradiation in paediatric CNS tumours.

Spontaneous coronary artery dissection: a Western Denmark Heart Registry study.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS) that associates with a high acute-phase mortality rate, whereas long-term outcome is less well described. OBJECTIVE: To describe the incidence, predictors, and prognosis of SCAD. DESIGN: Retrospective case-identification study from the Western Denmark Heart Registry and the database of the Forensic Institute at Aarhus University from 1999 through 2007. RESULTS: SCAD was documented in 22 of 32,869 (0.7 per thousand) angiograms in the angiographic registry. The SCAD incidence among cases of ACS was 22 of 11,175 (2.0 per thousand). None was seen in the forensic database. The mean age was 48.7 +/- 8.9 years (range: 37-71 years). Females constituted 17 of 22 (77%) patients and all had undergone one or more pregnancies; two cases occurred in the postpartum period. The left descending artery (LAD) was the predominant site of entry. The age distribution, prevalence of the cardiovascular risk factors, presence of coronary atherosclerosis, and entry of the dissection were comparable among genders. Treatment was percutaneous coronary intervention in 13 of 22 (59%), coronary artery bypass operation in 2 of 22 (9%), and medical treatment in 7 of 22 (32%) patients. The mean follow-up period was 3.6 +/- 2.9 years. One patient suffered from recurrent SCAD; another patient died suddenly. The MACE- (cardiac death, nonfatal myocardial infarction, and new revascularization) free survival was 81% after 24 months. CONCLUSION: SCAD is a rare disease that mainly affects younger women. Compared with earlier reports, the prognosis seems to be improved by early diagnosis and interventional treatment.

Comparative study of anchoring groups for molecular electronics: structure and conductance of Au-S-Au and Au-NH(2)-Au junctions.

The electrical properties of single-molecule junctions, consisting of an organic molecule coupled to metal electrodes, are sensitive to the detailed atomic structure of the molecule-metal contact. This, in turn, is determined by the anchoring group linking the molecule to the metal. With the aim of identifying and comparing the intrinsic properties of two commonly used anchoring groups, namely thiol and amine groups, we have calculated the atomic structure and conductance traces of different Au-S-Au and Au-NH(2)-Au nanojunctions using density functional theory (DFT). Whereas NH(2) shows a strong structural selectivity towards atop-gold configurations, S shows large variability in its bonding geometries. As a result, the conductance of the Au-NH(2)-Au junction is less sensitive to the structure of the gold contacts than the Au-S-Au junction. These findings support recent experiments which show that amine-bonded molecules exhibit more well-defined conductance properties than do thiol-bonded molecules.

Atherosclerosis in the human brachial artery.

OBJECTIVES: We sought to assess the prevalence of atherosclerotic lesions in the human brachial artery. BACKGROUND: Many investigators have recently studied endothelial and vascular function in the brachial circulation in humans to further their understanding of coronary artery disease and early atherogenesis. However, the prevalence of brachial atherosclerosis and its relation to coronary disease have never been documented. METHODS: Arterial segments from the brachial, common carotid and left anterior descending coronary arteries were obtained during autopsy in 52 consecutively examined subjects (35 men, 17 women; 21 to 79 years old, mean [+/-SD] age 51 +/- 16) and studied by light microscopy using standard histologic techniques. Severity of the atherosclerotic lesions was categorized as fatty streaks (grade 1), fibrous plaques (grade 2) and advanced lesions (grade 3). RESULTS: Atherosclerotic lesions of any grade were found in the brachial artery in 39 (75%) subjects, common carotid artery in 51 (98%) and left anterior descending coronary artery in 52 (100%), and the prevalence and severity of disease increased with age in all three arteries. The grade of lesion severity in the brachial and coronary arteries was significantly correlated (r = 0.41, p = 0.003), as was severity in the brachial and carotid arteries (r = 0.53, p = 0.0001) and the carotid and coronary arteries (r = 0.69, p = 0.0001). The correlation between the brachial artery and the left anterior descending coronary artery was highly significant in subjects < or = 50 years old (r = 0.54, p = 0.002), but not in those > or = 50 years old (r = 0.37, p = NS). CONCLUSIONS: Atherosclerosis is common in the human brachial artery and is significantly correlated with both coronary and carotid disease. These results suggest that the brachial circulation may serve as a reasonable "surrogate" for studying atherosclerosis, particularly in younger adults.

Circadian variation in bone resorption is not related to serum cortisol.

Serum osteocalcin, serum procollagen type I carboxyterminal propeptide (sPICP), and the urinary excretion of pyridinium crosslinks (biochemical markers of bone formation and resorption) all exhibit a circadian variation with a peak during the night. This study was performed to investigate the influence of the endogenous circadian rhythm in cortisol on the biochemical markers of bone turnover. Participants included 11 patients substituted with hydrocortisone due to either hypopituitarism (n = 7) or bilateral adrenalectomy (n = 4). Their daily tablet intake of hydrocortisone was divided in four equal doses in order to abrogate the known circadian variation in cortisol. 24 healthy postmenopausal women served as controls. The study design was performed over 24 h, with blood samples taken every 3 h, and urine collected in 3 h aliquots. Urinary pyridinium crosslinks (Pyr/ Cr, D-Pyr/Cr), serum osteocalcin (sOC), and serum PICP were measured. Patients without a circadian variation in cortisol had normal circadian variation in the urinary excretion of pyridinium crosslinks and sPICP, but no circadian rhythm in serum osteocalcin. We conclude that the etiology of the circadian rhythm in the biochemical markers of bone turnover is still unknown. This study indicates that the circadian variation in sOC can be controlled by the endogenous circadian variation in serum cortisol, whereas this hormone does not control the circadian variation in either the serum PICP or the urinary excretion in pyridinium crosslinks.

Volumetric and dosimetric evaluation of radiation treatment plans: radiation conformity index.

PURPOSE: The use of conformal radiation therapy has grown substantially during the last years since three-dimensional (3D) treatment planning systems with beams-eye-view planning has become commercially available. We studied the degree of conformity reached in clinical routines for some common diagnoses treated at our department by calculating a radiation conformity index (RCI). METHODS AND MATERIALS: The radiation conformity index, determined as the ratio between the target volume (PTV) and the irradiated volume, has been evaluated for 57 patients treated with 3D treatment plans. RESULTS AND CONCLUSION: The RCI was found to vary from 0.3 to 0.6 (average 0.4), a surprisingly low figure. The higher RCI is typical for pelvic treatments (e.g., prostate) and stereotactic treatments. The lower RCI is found for extended tumors, such as mammary carcinomas where the adjacent nodes are included. The latter is also valid for most lung cancer patients studied. The RCI gives a consistent method for quantifying the degree of conformity based on isodose surfaces and volumes. Care during interpretation of RCI must always be taken, since small changes in the minimum dose can dramatically change the treated volume.

A histomorphometric method for evaluating topographic differences in degree of early atherosclerosis within the human aorta.

The aim of the study was to develop an unbiased topographically oriented method of evaluating early atherosclerotic lesions in the aorta and to apply this to a series of human aortas from young adults. A systematic sampling procedure and histomorphometric analysis of intimal thickening is described. Results from a group of 15 young adults (aged 18-40 years) showed a characteristic pattern with increasing intimal thickening when moving distally from the thoracic to the upper and finally to the lower abdominal aorta, but also a shift in the localization of the most pronounced intimal thickening from the posterior to the anterior and back to the posterior aspect. This pattern was found in aortas both with minimal and with more pronounced atherosclerosis, and supports the view that the early intimal thickening precedes the atherosclerotic lesions and marks the sites of predilection for the more advanced disease processes. An increase in intimal thickness with age could be demonstrated in the aortas without overt atherosclerosis. The simple sampling procedure, well-defined sampling sites, and ability to demonstrate and quantitate differences in intimal thickening and plaque morphology make this method well suited for relating morphometric data to other parameters of interest when studying the etiology and dynamics of atherosclerotic disease.

Cortical bone cross-sectional osteon size in chronic pulmonary insufficiency and regional ischemic states.

Cross sectional osteon diameter (D) and Haversian canal diameter (d) were measured in undecalcified, unstained sections from the mid-diaphysis of femoral bones from 13 patients with long lasting chronic pulmonary insufficiency, 10 patients with unilateral thrombosis of the femoral artery and from sex- and age-matched normal controls. The cross sectional osteon radius (R = the distance travelled by osteoclats), the mean wall thickness (MWT = (D-d)/2 = distance travelled by osteoblasts) and the structural unit balance (B = R/MWT) were calculated. No significant differences were found in R, MWT og B between chronic pulmonary insufficiency patients and normal controls. Furthermore, no significant differences were found between thrombotic or non-thrombotic legs or between thrombotic legs and their normal controls. This part of the study does not support the concept that the distance travelled by the osteoclasts (R) depends on local supply of nutrients and/or removal of waste products. However, in all patients and controls R was larger in the inner zone than in the outer zone (p less than 0.01). This could be explained by the anatomy of the arterial supply to cortical bone supporting the above hypothesis.

DNA-index and stereological estimation of nuclear volume in primary and metastatic malignant melanomas: a comparative study with analysis of heterogeneity.

The aim of this study was to investigate the relationship between physical nuclear volume and ploidy level in malignant melanomas, and to analyse the heterogeneity of these two parameters among primary and corresponding secondary tumours. Unbiased stereological estimates of nuclear volume can be obtained objectively by point-sampled intercepts. Using this approach, the volume-weighted mean nuclear volume, nuclear vv, was estimated in ordinary histological sections from 34 primary cutaneous malignant melanomas and their corresponding 62 metastatic lesions. For comparison, DNA-indices (DI) were determined by flow cytometry in adjacent sections from the same paraffin-embedded tumours. Only a poor correlation was found between nuclear vv and DI (Kendall's tau = +0.21). The variability of nuclear vv among metastatic lesions was increased as compared to primary melanomas, whereas averaged mean values of nuclear vv did not differ significantly between the two types of neoplasms. Aneuploidy was not significantly associated with increased nuclear vv. Pronounced intra-patient heterogeneity of nuclear vv was disclosed among metastases and between the primary melanoma and the metastatic lesions. Likewise, no significant association between DI of primary and metastatic melanomas was demonstrated. Heterogeneity of nuclear vv and DI in malignant melanomas is in agreement with the theory of polyclonality.

Late nervous system disorders in cured malignant lymphoma: a clinical and neuropathological study.

A 53-year-old woman was treated for and cured of low grade malignant lymphoma, localized to the neck, by irradiation and chemotherapy. One year later she developed signs of damage to the spinal cord with slight paraparesis of the lower extremities, which remained stationary for seven years. Then, new and rapidly progressive central and peripheral neurological symptoms developed. About one year later the patient died. At autopsy a malignant glioma of the right temporal lobe and radiation damage to the spinal cord were found. Lymphocytic infiltrations in the peripheral nerves and muscles of the lower extremities were also seen. A severe neurogenic atrophy was present but no relapse of malignant lymphoma was found. Depressed immune defense is suggested to be the cause of the pathological changes of the nervous system in this case. The inflammation of the peripheral nerves might be due to activation of a latent virus infection.

Alcohol and drugs (medical and illicit) in fatal road accidents in a city of 300,000 inhabitants.

During a 1-year period all fatal road accidents in the police district of Aarhus, Denmark, were investigated regarding the presence of alcohol, medical drugs or narcotic substances, and the nature of the accident. Out of a total of 30 accidents 24 were investigated. Two thirds had been caused by the victim him- or herself. In one third of the accidents alcohol was present and considered an important contributory factor. Medical drugs and narcotic substances played a lesser role.

The diagnostic value of pericardial cytology. An analysis of 95 cases.

Cytologic specimens of 105 pericardial fluids collected from 95 cases during a seven-year period were reviewed. Clinical reports and descriptions of the histologic antemortem and postmortem specimens were correlated with the cytologic diagnoses, and the interobserver variation was estimated. Of the collected material, 48.4% was from patients suspected of having nonmalignant disorders, 40.0% was from patients with previously diagnosed carcinomas and 11.6% was from cases in which the etiology was unknown at the time of pericardiocentesis. Cytologic examination of the pericardial fluids revealed tumor cells in a sample from one patient suspected of having a heart disorder and in a sample from another patient with an obscure disease. Of the pericardial fluids from the cancer patients, 66.7% contained malignant cells; the most frequent primary site in these cases was the lung. Correlated with the histologic diagnosis, the specificity of cytology was 100%. The results prove that, in experienced hands, pericardial cytology is a valuable diagnostic tool.

Prevalence of cannabinoids in urine samples from forensic autopsies.

Urine samples from 393 forensic autopsies were tested for the presence of cannabinoids by means of the radio-immunoassay test kit from DPC, Los Angeles. Fifteen per cent were found positive, mainly men and young adults. Use of cannabis was found to be closely related to drug addiction, and thus in cannabis-positive drug addicts, non-natural manners and causes of death dominate. In non-addicts the prevalence of cannabis use was 7.5%, and in non-addicted cannabis users, manners and causes of death were not very different from those found in cannabis-negatives.

Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa.

OBJECTIVE: To examine the association between routine childhood vaccinations and survival among infants in Guinea-Bissau. DESIGN: Follow up study. PARTICIPANTS: 15 351 women and their children born during 1990 and 1996. SETTING: Rural Guinea-Bissau. MAIN OUTCOME MEASURES: Infant mortality over six months (between age 0-6 months and 7-13 months for BCG, diphtheria, tetanus, and pertussis, and polio vaccines and between 7-13 months and 14-20 months for measles vaccine). RESULTS: Mortality was lower in the group vaccinated with any vaccine compared with those not vaccinated, the mortality ratio being 0.74 (95% confidence interval 0.53 to 1.03). After cluster, age, and other vaccines were adjusted for, BCG was associated with significantly lower mortality (0.55 (0.36 to 0.85)). However, recipients of one dose of diphtheria, tetanus, and pertussis or polio vaccines had higher mortality than children who had received none of these vaccines (1.84 (1.10 to 3.10) for diphtheria, tetanus, and pertussis). Recipients of measles vaccine had a mortality ratio of 0.48 (0.27 to 0.87). When deaths from measles were excluded from the analysis the mortality ratio was 0.51 (0.28 to 0.95). Estimates were unchanged by controls for background factors. CONCLUSIONS: These trends are unlikely to be explained exclusively by selection biases since different vaccines were associated with opposite tendencies. Measles and BCG vaccines may have beneficial effects in addition to protection against measles and tuberculosis.

[Methanol poisoning in alcohol abusers]. / Traespritforgiftning hos alkoholmisbrugere.

Methanol (wood alcohol) is sold in Denmark only to factories and laboratories with a certified knowledge of the substance or to individuals holding a special licence. Methanol is nowadays used as a solvent or for syntheses only. During a six-year period three cases of methanol poisoning were found in a selected forensic material. A screening for alcohols is routinely performed in connection with all medicolegal autopsies when the presence of alcohols cannot be ruled out in advance. All three cases concerned men accustomed to a substantial intake of alcohol. Two of the cases were accidental deaths due to methanol poisoning. The third case was suicide committed by the ingestion of a herbicide containing methanol. Methanol poisonings are rare, but do still occur. It is, therefore, important for physicians to be aware of the symptoms and know the treatment.

[Blood pressure check-up--routine blood pressure measurements in a patient with arteriovenous shunt and under dialysis]. / Blodtrykskontrol--konventionel BT-måling hos dialysepatient med arteriovenøs shunt.

A case of untreated hypertension in a patient, where blood pressure could be measured in the right arm only is presented. At autopsy, the brachio-cephalic artery was found to be occluded explaining why blood pressure values were low. Significant left ventricular hypertrophy indicating high central blood pressure was found. Sudden death followed a spontaneous intracerebral bleeding. The value of conventional blood pressure measurement in patients with arteriovenous shunt because of chronic dialysis is discussed.

[Suicide among the elderly in the county of Arhus. A 10-year retrospective study of suicide among persons aged 65 and over]. / Selvmord hos aeldre i Arhus Amt. En 10-års retrospektiv underøgelse af selvmord hos personer over 65 år.

During a ten year period (1983 to 1992) 337 suicides (188 men and 149 women) were registered among people over 65 years of age in the county of Aarhus. The suicide rate (number of deaths per 100,000 living people) decreased during the period from 1983 to 1990. For men the rate was highest over the age of 80, whereas for women the rate was highest before the age of 70. The analyses showed, that the majority of the suicides were committed with violent methods. Previous attempts were registered in 25%. The decision to commit suicide was not associated with health conditions. The percentage of suicide victims living in nursing-homes was slightly higher than that of the background population. In 25% of the 116 suicides a farewell letter was found, despondency was slated as the main cause - not painful or incurable diseases. Prevention of suicide among elderly people is not clarified in this study.