Pencil beam scanning proton therapy for mediastinal lymphomas in deep inspiration breath-hold: a retrospective assessment of plan robustness.

PURPOSE/BACKGROUND: The aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment.  Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated. RESULTS: The TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs. CONCLUSION: PBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.

Transitioning from conventional photon therapy to proton therapy for primary brain tumors.

INTRODUCTION: Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT. METHOD: Adult patients with grade 2-3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment. RESULTS: Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p = .38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p = .016). The PT patients had a significantly better PFS and OS than the XRT patients (p = .025 and .035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p < .001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively. CONCLUSION: Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT.

Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019.

BACKGROUND: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. MATERIAL AND METHODS: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. RESULTS: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). CONCLUSION: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.

Living in limbo while one's identity is changing: Patients' existential experiences 6 months after a kidney transplantation with a living donor.

AIM: To investigate patients' existential experiences in everyday life after a kidney transplantation with a living donor. DESIGN: A qualitative study anchored in a hermeneutic-phenomenological approach inspired by Ricoeur's theory of narrative and interpretation. METHOD: Eleven patient interviews were conducted approximately 6 months after a kidney transplantation with a living donor. The interviews were conducted between August 2017-May 2019. Analysis and interpretation are based on Ricoeur's theory of interpretation. RESULTS: Four themes were identified: Experiencing bodily vulnerability while getting back to life; Feeling guilt while experiencing gratitude; Living in limbo while one's identity is changing; and Facing the future with hope while having reservations. CONCLUSION: This study reveals that patients experience multifaceted existential challenges in their everyday lives during the transition of the kidney transplantation process. Post-surgery complications for donors lead to feelings of guilt in patients; plus, they must adapt to a new existence, including a new identity. The patients feel they are in limbo, as they experience their existence as uncertain and their identity as unknown. IMPACT: The study highlights a need for developing a rehabilitation programme to address the individual and various existential challenges faced by patients who need to undergo a kidney transplantation.

Patients' perspective in the context of proton beam therapy: summary of a Nordic workshop.

INTRODUCTION: On 15-16 November 2019, the Skandion Clinic in Sweden hosted the first Nordic workshop on 'Patients' perspective in proton beam therapy'. The workshop was conducted to describe and compare the patient care in PBT clinics in the Nordic countries and to initiate a collaboration, with the target to ensure patient participation and reduce the risk of inequity of access by lowering the barriers for accepting PBT in a distant clinic. The overarching aim of this workshop was to describe and compare the use of patients' perspectives in the Nordic PBT clinics. MATERIAL AND METHODS: Twelve participants attended the workshop, representing Denmark, Norway and Sweden. The participants were registered nurses working in patient care, researchers, physicist and leaders of the Skandion Clinic. RESULTS: The consensus of the workshop was that systematic use of patient experiences on individual and group level is essential for developing clinical practice and understanding the overall effects of PBT. A difference in how the Nordic countries use patient experiences in clinical practise was found. The importance of lowering the barriers for participation in national proton trials and proton treatment were emphasized, however, there is a lack of knowledge about individual and organizational barriers to accepting PBT, and further research is therefore needed. CONCLUSION: Collaboration between the Nordic countries regarding patients' perspectives in the context of PBT is of importance to compare national differences as well as to find similarities, but most importantly to learn from each other and to improve patient care. Nordic collaboration with focus on systematic collection of patient-reported outcomes in the context of PBT is unique. Collaboration in research offers the possibility to increase the inclusion of patients' perspectives in study protocols.

Analgesic Outcomes in a Danish Acute Care Hospital Following Electronic Prescribing and Analgesic Self-Administration.

BACKGROUND: Despite the long-term consequences of poorly controlled postoperative pain, inadequate pain control remains a problem. AIMS: To improve the quality of postoperative pain management, the study site, an acute care hospital in Denmark, introduced electronic prescribing with standard order-sets, and allowed patients to self-administer analgesia. This study aimed to describe analgesic prescribing, prescriptions for multimodal analgesia, analgesic administration, and patients' pain experience, in this context. DESIGN: Point-prevalence survey. SETTINGS: One Danish regional hospital. PARTICIPANTS: Consecutive sample of 286 surgical inpatients comprising 65 orthopaedic, 41 gynaecological, 57 urology and 123 gastrointestinal patients. METHODS: We evaluated the quality of postoperative pain management on four postoperative surgical wards using: (1) the Revised American Pain Society Patient Outcome Questionnaire; and (2) patient chart audit. RESULTS: Overall, 89.2% of patients were prescribed a fixed analgesic and 71.7% were prescribed fixed analgesics in multimodal combination. Patterns of multimodal prescribing and administration varied significantly across surgical groups. Patients received 87.7% of available fixed prescriptions and 22.5% of available analgesics prescribed 'as needed'. However, patients' worst pain intensity was high (mean = 5.8/10, SD = 2) and 73.4% reported moderate-to-severe worst pain during the previous 24-hours. Patients who self-administered medications used significantly more fixed-schedule paracetamol (p = .018), non-steroidal anti-inflammatory drugs (p = .001), weak (p = .035) and strong (p < .001) opioids. CONCLUSIONS: The availability of multimodal analgesia was high following the introduction of electronic prescribing. However, gaps remain in the administration of both fixed and 'as needed' analgesics for postoperative patients. Findings suggested that allowing patients to self-administer analgesia may increase compliance with fixed schedule prescriptions.

Living in one's own world, while life goes on: Patients' experiences prior to a kidney transplantation with a living donor.

AIMS AND OBJECTIVES: To investigate patients' existential experiences in everyday life prior to a kidney transplantation with a living donor. BACKGROUND: Kidney transplantation is a well-established treatment for patients with end-stage kidney disease. The prevalence of patients living with end-stage renal disease is increasing. Simultaneously, kidney transplantations with a living donor are increasing. However, patients experience challenging existential aspects concerning kidney transplantation. DESIGN: A qualitative study with a hermeneutic-phenomenological approach inspired by Ricoeur was chosen. METHODS: Fourteen interviews with patients living with end-stage kidney disease were conducted 7-14 days before a planned kidney transplantation with a living donor. Analysis and interpretation were based on Ricoeur's theory of interpretation. We applied the Criteria for Reporting Qualitative Research (see Appendix S1). RESULTS: Four themes were identified: living with subjective feelings of illness while objectifying the body; living in one's own world while the world outside goes on; feeling grateful while being concerned for the donor; and hoping for the best, while preparing for the worst. CONCLUSION: Patients' existential challenges are multifaceted. Patients articulate their kidney function in numeric terms, trying to make the invisible visible for themselves and others. Sustaining normality becomes important for patients, and the waiting time from donor evaluation to transplantation triggers excitement, hope and frustration. RELEVANCE TO CLINICAL PRACTICE: The results increase insights into individuals' existential experiences in their everyday lives. Hereby, the results articulate the need for support from health professionals prior to a kidney transplantation.

Comparative treatment planning study for mediastinal Hodgkin's lymphoma: impact on normal tissue dose using deep inspiration breath hold proton and photon therapy.

BACKGROUND: Late effects induced by radiotherapy (RT) are of great concern for mediastinal Hodgkin's lymphoma (HL) patients and it is therefore important to reduce normal tissue dose. The aim of this study was to investigate the impact on the normal tissue dose and target coverage, using various combinations of intensity modulated proton therapy (IMPT), volumetric modulated arc therapy (VMAT) and 3-dimensional conformal RT (3D-CRT), planned in both deep inspiration breath hold (DIBH) and free breathing (FB). MATERIAL AND METHODS: Eighteen patients were enrolled in this study and planned with involved site RT. Two computed tomography images were acquired for each patient, one during DIBH and one during FB. Six treatment plans were created for each patient; 3D-CRT in FB, 3D-CRT in DIBH, VMAT in FB, VMAT in DIBH, IMPT in FB and IMPT in DIBH. Dosimetric impact on the heart, left anterior descending (LAD) coronary artery, lungs, female breasts, target coverage, and also conformity index and integral dose (ID), was compared between the different treatment techniques. RESULTS: The use of DIBH significantly reduced the lung dose for all three treatment techniques, however, no significant difference in the dose to the female breasts was observed. Regarding the heart and LAD doses, large individual variations were observed. For VMAT, the mean heart and LAD doses were significantly reduced using DIBH, but no significant difference was observed for 3D-CRT and IMPT. Both IMPT and VMAT resulted in improved target coverage and more conform dose distributions compared to 3D-CRT. IMPT generally showed the lowest organs at risk (OAR) doses and significantly reduced the ID compared to both 3D-CRT and VMAT. CONCLUSIONS: The majority of patients benefited from treatment in DIBH, however, the impact on the normal tissue dose was highly individual and therefore comparative treatment planning is encouraged. The lowest OAR doses were generally observed for IMPT in combination with DIBH.

Assessment of volume segmentation in radiotherapy of adolescents; a treatment planning study by the Swedish Workgroup for Paediatric Radiotherapy.

BACKGROUND AND PURPOSE: The variability in target delineation for similar cases between centres treating paediatric and adolescent patients, and the apparent differences in interpretation of radiotherapy guidelines in the treatment protocols encouraged us to perform a dummy-run study as a part of our quality assurance work. The aim was to identify and quantify differences in the segmentation of target volumes and organs at risk (OARs) and to analyse the treatment plans and dose distributions. MATERIALS AND METHODS: Four patient cases were selected: Wilm's tumour, Hodgkin's disease, rhabdomyosarcoma of the prostate and chordoma of the skull base. The five participating centres received the same patient-related material. They introduced the cases in their treatment planning system, delineated target volumes and OARs and created treatment plans. Dose-volume histograms were retrieved for relevant structures and volumes and dose metrics were derived and compared, e.g. target volumes and their concordance, dose homogeneity index (HI), treated and irradiated volumes, remaining volume at risk and relevant Vx and Dx values. RESULTS: We found significant differences in target segmentation in the majority of the cases. The planning target volumes (PTVs) varied two- to four-fold and conformity indices were in the range of 0.3-0.6. This resulted in large variations in dose distributions to OARs as well as in treated and irradiated volumes even though the treatment plans showed good conformity to the PTVs. Potential reasons for the differences in target delineation were analysed. CONCLUSION: Considerations of the growing child and difficulties in interpretation of the radiotherapy information in the treatment protocols were identified as reasons for the variation. As a result, clarified translated detailed radiotherapy guidelines for paediatric/adolescent patients have been recognised as a way to reduce this variation.

Feasibility and constraints of Bragg peak FLASH proton therapy treatment planning.

Introduction: FLASH proton therapy (FLASH-PT) requires ultra-high dose rate (≥ 40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the in silico results produced to plans for intensity modulated proton therapy (IMPT). Materials and method: Bragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain. FLASH-PT beams were simulated using monoenergetic spot-scanned protons traversing through a conformal energy modulator, a range shifter, and an aperture. A dose rate constraint of ≥ 40 Gy/s was included in each FLASH-PT plan optimisation. Results: Space limitations in the FLASH-PT adapted beam nozzle imposed a maximum target width constraint, excluding 4 cases from the study. FLASH-PT plans did not satisfy the imposed target dose constraints (D95% ≥ 95% and D2%≤ 105%) but achieved clinically acceptable doses to organs at risk (OARs). IMPT plans adhered to all target and OAR dose constraints. FLASH-PT plans showed a reduction in both target homogeneity (p < 0.001) and dose conformity (non-significant) compared to IMPT. Conclusion: Without accounting for a sparing effect, IMPT plans were superior in target coverage, dose conformity, target homogeneity, and OAR sparing compared to FLASH-PT. Further research is warranted in treatment planning optimisation and beam delivery for clinical implementation of Bragg peak FLASH-PT.

Patterns of practice of image guided particle therapy for cranio-spinal irradiation: A site specific multi-institutional survey of European Particle Therapy Network.

PURPOSE: To investigate the current practice patterns in image-guided particle therapy (IGPT) for cranio-spinal irradiation (CSI). METHODS: A multi-institutional survey was distributed to European particle therapy centres to analyse all aspects of IGPT. Based on the survey results, a Delphi consensus analysis was developed to define minimum requirements and optimal workflow for clinical practice. The centres participating in the institutional survey were invited to join the Delphi process. RESULTS: Eleven centres participated in the survey. Imaging for treatment planning was rather similar among the centres with Computed Tomography (CT) being the main modality. For positioning verification, 2D IGPT was more commonly used than 3D IGPT. Two centres performed routinely imaging for plan adaptation, by the rest ad hoc. Eight centres participated in the Delphi consensus analysis. The full consensus was reached on the use of CT imaging without contrast for treatment planning and the role of magnetic resonance imaging (MRI) in target and organs-at-risk delineation. There was an agreement on the necessity to perform patient position verification and correction before each isocentre. The most important outcome was the clear need for standardization and harmonization of the workflow. CONCLUSION: There were differences in CSI IGPT clinical practice among the European particle therapy centres. Moreover, the optimal workflow as identified by experts was not yet reached. There is a strong need for consensus guidelines. The state-of-the-art imaging technology and protocols need to be implemented into clinical practice to improve the quality of IGPT for CSI.

Quality assessment of radiotherapy in the prospective randomized SENOMAC trial.

BACKGROUND AND PURPOSE: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. MATERIALS AND METHODS: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail. RESULTS: CRF-data and RT plans agreed in 99.3 % (breast/chest wall) and in 96.6 % of patients (regional RT). Congruence for whether level I was an intended RT target was lower (78 %). In accordance with Danish national guidelines, level I was more often an intended target in the SLN biopsy only arm (N = 334/611, 55 %,) than in the cALND arm (N = 174/565, 31 %,). When an intended target, level I received prescribed dose to 100 % (IQR 98-100 %) of the volume. However, even when not an intended target, full dose was delivered to > 80 % of level I (IQR 75-90 %). The intentional inclusion of level I in the target volume more than doubled the dose received by ≥ 50 % of the humeral head. CONCLUSION: Congruence between CRF data and RT plans was excellent. Level I received a high dose coverage even when not intentionally included in the target. Including level I in target significantly increased dose to the humeral head.

Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy.

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden.

INTRODUCTION: The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life. METHODS AND ANALYSIS: PRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints. ETHICS AND DISSEMINATION: To implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05190172).

The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of young sudden unexplained death cases.

INTRODUCTION: Sudden unexplained death account for one-third of all sudden natural deaths in the young (1-35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long-QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide setting. METHODS: DNA for genetic testing was available for 44 cases of sudden unexplained death in Denmark in the period 2000-2006 (equaling 33% of all cases of sudden unexplained death in the age group). KCNQ1, KCNH2, and SCN5A were sequenced and in vitro electrophysiological studies were performed on novel mutations. RESULTS: In total, 5 of 44 cases (11%) carried a mutation in 1 of the 3 genes corresponding to 11% of all investigated cases (R190W KCNQ1, F29L KCNH2 (2 cases), P297S KCNH2 and P1177L SCN5A). P1177L SCN5A has not been reported before. In vitro electrophysiological studies of P1177L SCN5A revealed an increased sustained current suggesting a LQTS phenotype. CONCLUSION: In a nationwide setting, the genetic investigation of an unselected population of sudden unexplained death cases aged 1-35 years finds a lower than expected number of mutations compared to referred populations previously reported. We therefore conclude that the prevalence of mutations in the 3 major LQTS associated genes may not be as abundant as previously estimated.

Differences in investigations of sudden unexpected deaths in young people in a nationwide setting.

BACKGROUND: Inherited disease may be causative in many young sudden unexpected death cases. Autopsy is essential in the counselling of the bereaved, as the family of the victim may be at risk too. In a nationwide setting operating under the same set of laws, we hypothesized that regional differences exist in the investigation of young persons dying suddenly and unexpectedly. METHODS AND RESULTS: All deaths in persons aged 1-35 years in Denmark in 2000-2006 were included. Death certificates were read independently by two physicians. External examination as well as autopsy status was retrieved. Significant regional differences were found regarding external examinations and autopsy frequencies. Ratios of conducted external examinations varied between 63% and 93% (p = 0.004). Autopsy ratios varied between 60% and 88% (p = 0.001). In urban areas, external examinations and autopsies were more often conducted than in rural areas. In East Denmark, there were more external examinations resulting in a forensic autopsy, and there was a higher overall autopsy rate compared to West Denmark. CONCLUSION: Despite operating under the same set of laws, we document significant regional differences in forensic investigations of young persons suffering a sudden unexpected death. This is probably not unique for Denmark although no data exist to confirm that. The results are worrying and call for a revision of the way these deaths are handled. Mandatory autopsy in sudden unexpected death in young persons is warranted as a thorough investigation of the death may help the clinician in guidance of the relatives in relation to hereditary diseases.

Nationwide study of sudden cardiac death in persons aged 1-35 years.

AIMS: The aim of this investigation was to study the incidence of sudden cardiac death (SCD) in persons aged 1-35 years in a nationwide setting (5.38 million people) by systematic evaluation of all deaths. METHODS AND RESULTS: All deaths in persons aged 1-35 years in Denmark in 2000-06 were included. Death certificates were read independently by two physicians. The National Patient Registry was used to retrieve information on prior medical history. All autopsy reports were read and the cause of death was revised based on autopsy findings. We identified 625 cases of sudden unexpected death (10% of all deaths), of which 156 (25%) were not autopsied. Of the 469 autopsied cases, 314 (67%) were SCD. The most common cardiac cause of death was ischaemic heart disease (13%); 29% of autopsied sudden unexpected death cases were unexplained. In 45% of SCD cases, the death was witnessed; 34% died during sleep; 89% were out-of-hospital deaths. Highest possible incidence rate of SCD in the young was 2.8 per 100 000 person-years including non-autopsied cases of sudden unexpected death. Excluding those, the incidence rate declined to 1.9 per 100 000 person-years. CONCLUSIONS: A total of 7% of all deaths in the young can be attributed to SCD, when including non-autopsied cases (autopsy ratio 75%). The incidence rate of SCD in the young of 2.8 per 100 000 person-years is higher than previously reported.

Sudden unexpected death in infancy in Denmark.

BACKGROUND: Incidence of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) differs among studies and non-autopsied cases are difficult to assess. OBJECTIVES: To investigate causes of sudden death in infancy in a nationwide setting. Validate the use of the ICD-10 code for SIDS (R95) in the Danish Cause of Death registry. DESIGN: A retrospective analysis of all infant deaths (< 1 year of age) in Denmark in 2000-2006. All death certificates and autopsy reports were read. RESULTS: We identified 192 SUDI cases (10% of total deaths, 0.42 per 1000 births) with autopsy performed in 87% of cases. In total, 49% of autopsied SUDI cases were defined as SIDS (5% of all deaths, 0.22 per 1000 births); Cardiac cause of death was denoted in 24% of cases. The Danish Cause of Death Registry misclassified 30% of SIDS cases. CONCLUSIONS: A large proportion of infant deaths are SUDI, and the majority of these are caused by cardiac disease or SIDS. Autopsy is not always performed and valuable information is subsequently lost. Cause of Death registry data is not accurate in describing SIDS.

Complications of the tension-free vaginal tape procedure for stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The purpose of the study was to determine the intraoperative and immediate postoperative complications of tension-free vaginal tapes (TVTs) and risk factors contributing to these. METHODS: The study was a retrospective cohort study of 778 TVT procedures. RESULTS: The intraoperative and postoperative complications from the study are as follows: Intraoperative complications included bladder perforation (6.6%), blood loss requiring transfusion (0.6%), and laparotomy (0.1%). Postoperatively, 3.1% of patients developed UTI, while 56.0% had difficulty voiding, and 16.6% had retention. Upon discharge, 54.8% of patients voided, 34.3% self-catheterized, and 8.0% had indwelling catheters. Surgeons responsible for more than 100 TVT procedures had one third the odds of a bladder perforation. Previous incontinence or prolapse surgery were risk factors for bladder perforation. Women with voiding dysfunction preoperatively had a 1.80-fold odds of difficulty postoperatively. CONCLUSION: Bladder perforation and postoperative retention are the most common complications of TVTs. Risk factors for perforation include less frequent TVT performance and previous prolapse, or incontinence surgery. Preexisting voiding dysfunction leads to postoperative retention.