Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study

Mortality among HIV-infected persons is decreasing, and causes of death are changing. Classification of deaths is hampered because of low autopsy rates, frequent deaths outside of hospitals, and shortcomings of International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding.

Causes of death and determinants of outcome in critically ill patients

INTRODUCTION: Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients. METHODS: Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods. RESULTS: Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively). CONCLUSION: In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.

The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism

Although previous studies have provided evidence that the majority of deaths following an acute pulmonary embolism (PE) directly relate to the PE, more recent registries and cohort studies suggest otherwise.

Postmortem whole-body MRI in traumatic causes of death

The aim of this study was to determine the sensitivity and specificity of postmortem whole-body MRI for typical injuries resulting from traumatic causes of death.

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Classification of thoracolumbar fractures and dislocations

A classification of injuries is necessary in order to develop a common language for treatment indications and outcomes. Several classification systems have been proposed, the most frequently used is the Denis classification. The problem of this classification system is that it is based on an assumption, which is anatomically unidentifiable: the so-called middle column. For this reason, few years ago, a group of spine surgeons has developed a new classification system, which is based on the severity of the injury. The severity is defined by the pathomorphological findings, the prognosis in terms of healing and potential of neurological damage. This classification is based on three major groups: A = isolated anterior column injuries by axial compression, B = disruption of the posterior ligament complex by distraction posteriorly, and group C = corresponding to group B but with rotation. There is an increasing severity from A to C, and within each group, the severity usually increases within the subgroups from .1, .2, .3. All these pathomorphologies are supported by a mechanism of injury, which is responsible for the extent of the injury. The type of injury with its groups and subgroups is able to suggest the treatment modality.

Inhibition of tissue transglutaminase sensitizes TRAIL-resistant lung cancer cells through upregulation of death receptor 5

Tissue transglutaminase (TG2) is implicated in cellular processes such as apoptosis and cell migration. Its acyl transferase activity cross-links certain proteins, among them transcription factors were described. We show here that the TG2 inhibitor KCC009 reversed resistance to tumor necrosis factor-related apoptosis-inducing factor (TRAIL) in lung cancer cells. Sensitization required upregulation of death receptor 5 (DR5) but not of death receptor 4. Upregulation of DR5 involved the first intron of the DR5 gene albeit it was independent from p53 and nuclear factor kappa B. In conclusion, inhibition of tissue transglutaminase provides an interesting strategy for sensitization to TRAIL-induced apoptosis in p53-deficient lung cancer cells.

Problems in functioning from the patient perspective using the International Classification of Functioning, Disability and Health (ICF) as a reference

We conducted a qualitative, multicenter study using a focus group design to explore the lived experiences of persons with any kind of primary sleep disorder with regard to functioning and contextual factors using six open-ended questions related to the International Classification of Functioning, Disability and Health (ICF) components. We classified the results using the ICF as a frame of reference. We identified the meaningful concepts within the transcribed data and then linked them to ICF categories according to established linking rules. The six focus groups with 27 participants yielded a total of 6986 relevant concepts, which were linked to a total of 168 different second-level ICF categories. From the patient perspective, the ICF components: (1) Body Functions; (2) Activities & Participation; and (3) Environmental Factors were equally represented; while (4) Body Structures appeared poignantly less frequently. Out of the total number of concepts, 1843 concepts (26%) were assigned to the ICF component Personal Factors, which is not yet classified but could indicate important aspects of resource management and strategy development of those who have a sleep disorder. Therefore, treatment of patients with sleep disorders must not be limited to anatomical and (patho-)physiological changes, but should also consider a more comprehensive view that includes patient's demands, strategies and resources in daily life and the contextual circumstances surrounding the individual.

Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data

In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM).

Identification of problems in functioning of people with sleep disorders in a clinical setting using the International Classification of Functioning Disability and Health (ICF) Checklist

We conducted an explorative, cross-sectional, multi-centre study in order to identify the most common problems of people with any kind of (primary) sleep disorder in a clinical setting using the International Classification of Functioning, Disability and Health (ICF) as a frame of reference. Data were collected from patients using a structured face-to-face interview of 45-60 min duration. A case record form for health professionals containing the extended ICF Checklist, sociodemographic variables and disease-specific variables was used. The study centres collected data of 99 individuals with sleep disorders. The identified categories include 48 (32%) for body functions, 13 (9%) body structures, 55 (37%) activities and participation and 32 (22%) for environmental factors. 'Sleep functions' (100%) and 'energy and drive functions', respectively, (85%) were the most severely impaired second-level categories of body functions followed by 'attention functions' (78%) and 'temperament and personality functions' (77%). With regard to the component activities and participation, patients felt most restricted in the categories of 'watching' (e.g. TV) (82%), 'recreation and leisure' (75%) and 'carrying out daily routine' (74%). Within the component environmental factors the categories 'support of immediate family', 'health services, systems and policies' and 'products or substances for personal consumption [medication]' were the most important facilitators; 'time-related changes', 'light' and 'climate' were the most important barriers. The study identified a large variety of functional problems reflecting the complexity of sleep disorders. The ICF has the potential to provide a comprehensive framework for the description of functional health in individuals with sleep disorders in a clinical setting.

Unique paleopathology in a pre-Columbian mummy remnant from Southern Peru--severe cervical rotation trauma with subluxation of the axis as cause of death

We describe the multidisciplinary findings in a pre-Columbian mummy head from Southern Peru (Cahuachi, Nazca civilisation, radiocarbon dating between 120 and 750 AD) of a mature male individual (40-60 years) with the first two vertebrae attached in pathological position. Accordingly, the atlanto-axial transition (C1/C2) was significantly rotated and dislocated at 38° angle associated with a bulging brownish mass that considerably reduced the spinal canal by circa 60%. Using surface microscopy, endoscopy, high-resolution multi-slice computer tomography, paleohistology and immunohistochemistry, we identified an extensive epidural hematoma of the upper cervical spinal canal-extending into the skull cavity-obviously due to a rupture of the left vertebral artery at its transition between atlas and skull base. There were no signs of fractures of the skull or vertebrae. Histological and immunohistochemical examinations clearly identified dura, brain residues and densely packed corpuscular elements that proved to represent fresh epidural hematoma. Subsequent biochemical analysis provided no evidence for pre-mortal cocaine consumption. Stable isotope analysis, however, revealed significant and repeated changes in the nutrition during his last 9 months, suggesting high mobility. Finally, the significant narrowing of the rotational atlanto-axial dislocation and the epidural hematoma probably caused compression of the spinal cord and the medulla oblongata with subsequent respiratory arrest. In conclusion, we suggest that the man died within a short period of time (probably few minutes) in an upright position with the head rotated rapidly to the right side. In paleopathologic literature, trauma to the upper cervical spine has as yet only very rarely been described, and dislocation of the vertebral bodies has not been presented.

Death by biscuit--exhumation, post-mortem CT, and revision of the cause of death one year after interment

We describe a case of exhumation, performed to investigate the circumstances and cause of death, one year after burial. Post mortem computed tomography (PMCT) revealed a mass in the pharynx. Imaging directed the subsequent forensic autopsy to careful retrieval of a foreign body. Histological analysis revealed a non-cellular composition. The detection of foreign material in the pharynx and its composition indicated accidental, rather than natural death, secondary to choking on food. This unusual case illustrates how post mortem imaging can significantly contribute to forensic investigation and stresses the importance of interdisciplinary collaboration between forensic pathologists and radiologists.

Estimating loss to follow-up in HIV-infected patients on antiretroviral therapy: the effect of the competing risk of death in Zambia and Switzerland

Background Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. Methods and Findings HIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. Conclusions In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings.