Changes in End-of-Life Practices in European Intensive Care Units From 1999 to 2016.

IMPORTANCE: End-of-life decisions occur daily in intensive care units (ICUs) around the world, and these practices could change over time. OBJECTIVE: To determine the changes in end-of-life practices in European ICUs after 16 years. DESIGN, SETTING, AND PARTICIPANTS: Ethicus-2 was a prospective observational study of 22 European ICUs previously included in the Ethicus-1 study (1999-2000). During a self-selected continuous 6-month period at each ICU, consecutive patients who died or had any limitation of life-sustaining therapy from September 2015 until October 2016 were included. Patients were followed up until death or until 2 months after the first treatment limitation decision. EXPOSURES: Comparison between the 1999-2000 cohort vs 2015-2016 cohort. MAIN OUTCOMES AND MEASURES: End-of-life outcomes were classified into 5 mutually exclusive categories (withholding of life-prolonging therapy, withdrawing of life-prolonging therapy, active shortening of the dying process, failed cardiopulmonary resuscitation [CPR], brain death). The primary outcome was whether patients received any treatment limitations (withholding or withdrawing of life-prolonging therapy or shortening of the dying process). Outcomes were determined by senior intensivists. RESULTS: Of 13 625 patients admitted to participating ICUs during the 2015-2016 study period, 1785 (13.1%) died or had limitations of life-prolonging therapies and were included in the study. Compared with the patients included in the 1999-2000 cohort (n = 2807), the patients in 2015-2016 cohort were significantly older (median age, 70 years [interquartile range {IQR}, 59-79] vs 67 years [IQR, 54-75]; P < .001) and the proportion of female patients was similar (39.6% vs 38.7%; P = .58). Significantly more treatment limitations occurred in the 2015-2016 cohort compared with the 1999-2000 cohort (1601 [89.7%] vs 1918 [68.3%]; difference, 21.4% [95% CI, 19.2% to 23.6%]; P < .001), with more withholding of life-prolonging therapy (892 [50.0%] vs 1143 [40.7%]; difference, 9.3% [95% CI, 6.4% to 12.3%]; P < .001), more withdrawing of life-prolonging therapy (692 [38.8%] vs 695 [24.8%]; difference, 14.0% [95% CI, 11.2% to 16.8%]; P < .001), less failed CPR (110 [6.2%] vs 628 [22.4%]; difference, -16.2% [95% CI, -18.1% to -14.3%]; P < .001), less brain death (74 [4.1%] vs 261 [9.3%]; difference, -5.2% [95% CI, -6.6% to -3.8%]; P < .001) and less active shortening of the dying process (17 [1.0%] vs 80 [2.9%]; difference, -1.9% [95% CI, -2.7% to -1.1%]; P < .001). CONCLUSIONS AND RELEVANCE: Among patients who had treatment limitations or died in 22 European ICUs in 2015-2016, compared with data reported from the same ICUs in 1999-2000, limitations in life-prolonging therapies occurred significantly more frequently and death without limitations in life-prolonging therapies occurred significantly less frequently. These findings suggest a shift in end-of-life practices in European ICUs, but the study is limited in that it excluded patients who survived ICU hospitalization without treatment limitations.

Agreement With Consensus Statements on End-of-Life Care: A Description of Variability at the Level of the Provider, Hospital, and Country.

OBJECTIVES: To develop an enhanced understanding of factors that influence providers' views about end-of-life care, we examined the contributions of provider, hospital, and country to variability in agreement with consensus statements about end-of-life care. DESIGN AND SETTING: Data were drawn from a survey of providers' views on principles of end-of-life care obtained during the consensus process for the Worldwide End-of-Life Practice for Patients in ICUs study. SUBJECTS: Participants in Worldwide End-of-Life Practice for Patients in ICUs included physicians, nurses, and other providers. Our sample included 1,068 providers from 178 hospitals and 31 countries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined views on cardiopulmonary resuscitation and withholding/withdrawing life-sustaining treatments, using a three-level linear mixed model of responses from providers within hospitals within countries. Of 1,068 providers from 178 hospitals and 31 countries, 1% strongly disagreed, 7% disagreed, 11% were neutral, 44% agreed, and 36% strongly agreed with declining to offer cardiopulmonary resuscitation when not indicated. Of the total variability in those responses, 98%, 0%, and 2% were explained by differences among providers, hospitals, and countries, respectively. After accounting for provider characteristics and hospital size, the variance partition was similar. Results were similar for withholding/withdrawing life-sustaining treatments. CONCLUSIONS: Variability in agreement with consensus statements about end-of-life care is related primarily to differences among providers. Acknowledging the primary source of variability may facilitate efforts to achieve consensus and improve decision-making for critically ill patients and their family members at the end of life.

Seeking worldwide professional consensus on the principles of end-of-life care for the critically ill. The Consensus for Worldwide End-of-Life Practice for Patients in Intensive Care Units (WELPICUS) study.

Great differences in end-of-life practices in treating the critically ill around the world warrant agreement regarding the major ethical principles. This analysis determines the extent of worldwide consensus for end-of-life practices, delineates where there is and is not consensus, and analyzes reasons for lack of consensus. Critical care societies worldwide were invited to participate. Country coordinators were identified and draft statements were developed for major end-of-life issues and translated into six languages. Multidisciplinary responses using a web-based survey assessed agreement or disagreement with definitions and statements linked to anonymous demographic information. Consensus was prospectively defined as >80% agreement. Definitions and statements not obtaining consensus were revised based on comments of respondents, and then translated and redistributed. Of the initial 1,283 responses from 32 countries, consensus was found for 66 (81%) of the 81 definitions and statements; 26 (32%) had >90% agreement. With 83 additional responses to the original questionnaire (1,366 total) and 604 responses to the revised statements, consensus could be obtained for another 11 of the 15 statements. Consensus was obtained for informed consent, withholding and withdrawing life-sustaining treatment, legal requirements, intensive care unit therapies, cardiopulmonary resuscitation, shared decision making, medical and nursing consensus, brain death, and palliative care. Consensus was obtained for 77 of 81 (95%) statements. Worldwide consensus could be developed for the majority of definitions and statements about end-of-life practices. Statements achieving consensus provide standards of practice for end-of-life care; statements without consensus identify important areas for future research.

Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients.

BACKGROUND: We compared two recently developed immunoassays for serum thymidine kinase 1 (TK1) activity: one manual assay (DiviTum, Biovica(®)) and one fully automated assay (Liaison, Diasorin(®)). METHODS: The study included 368 women: 149 healthy blood donors (control), 59 patients with benign breast disease (BBD) and 160 patients with primary breast cancer (BC). RESULTS: A regression analysis of the Liaison (y) and DiviTum (x) assays for all three groups yielded the equation y=3.93+0.03x (r=0.85, n=368). The r-value in BC was higher than in control and BBD (0.90 vs. 0.81 and 0.64). The correlation between the two assays for TK1 values above the cut-off was higher compared to that below (0.88 and 0.59). Breakdown of the BBD group into subgroups with proliferative and non-proliferative lesions was effective only with the measurement of TK1 with DiviTum assay (p=0.03). The TK1 activity determined preoperatively in BC patients with DiviTum and Liaison assays was significantly associated with T-stage (for both p=0.01), presence of vascular invasion (p=0.002 and p=0.02), lack of estrogen receptor (ER) (p=0.001 and p=0.01) and progesterone receptor (PR) (p=0.01 and p=0.03) expression. Only TK1 analyzed with the DiviTum assay was associated with tumor grade and molecular subtype of BC (p=0.02 and p=0.003). Multivariate Cox proportional hazards analyses demonstrated that T-stage, PR status and TK1 activity measured by both methods (DiviTum, RR=3.0, p=0.02 and Liaison, RR=3.1, p=0.01) were independent predictors of disease recurrence. CONCLUSIONS: In spite of differences observed between TK1 activity measured by the DiviTum and Liaison assays, both of them may be used for recurrence prediction in preoperative evaluation of BC patients.

Are religion and religiosity important to end-of-life decisions and patient autonomy in the ICU? The Ethicatt study.

PURPOSE: This study explored differences in end-of-life (EOL) decisions and respect for patient autonomy of religious members versus those only affiliated to that particular religion (affiliated is a member without strong religious feelings). METHODS: In 2005 structured questionnaires regarding EOL decisions were distributed in six European countries to ICUs in 142 hospital ICUs. This sub-study of the original data analyzed answers from Protestants, Catholics and Jews. RESULTS: A total of 304 physicians, 386 nurses, 248 patients and 330 family members were included in the study. Professionals wanted less treatment (ICU admission, CPR, ventilator treatment) than patients and family members. Religious respondents wanted more treatment and were more in favor of life prolongation, and they were less likely to want active euthanasia than those affiliated. Southern nurses and doctors favored euthanasia more than their Northern colleagues. Three quarters of doctors and nurses would respect a competent patient's refusal of a potentially life-saving treatment. No differences were found between religious and affiliated professionals regarding patient's autonomy. Inter-religious differences were detected, with Protestants most likely to follow competent patients' wishes and the Jewish respondents least likely to do so, and Jewish professionals more frequently accepting patients' wishes for futile treatment. However, these findings on autonomy were due to regional differences, not religious ones. CONCLUSIONS: Health-care professionals, families and patients who are religious will frequently want more extensive treatment than affiliated individuals. Views on active euthanasia are influenced by both religion and region, whereas views on patient autonomy are apparently more influenced by region.

The Eldicus prospective, observational study of triage decision making in European intensive care units: part I--European Intensive Care Admission Triage Scores.

OBJECTIVE: Life and death triage decisions are made daily by intensive care unit physicians. Scoring systems have been developed for prognosticating intensive care unit mortality but none for intensive care unit triage. The objective of this study was to develop an intensive care unit triage decision rule based on 28-day mortality rates of admitted and refused patients. DESIGN: Prospective, observational study of triage decisions from September 2003 until March 2005. SETTING: Eleven intensive care units in seven European countries. PATIENTS: All patients >18 yrs with a request for intensive care unit admission. INTERVENTIONS: Admission or rejection to an intensive care unit. MEASUREMENTS AND MAIN RESULTS: Clinical, laboratory, and physiological variables and data from severity scores were collected. Separate scores for accepted and rejected patients with 28-day mortality end point were built. Values for variables were grouped into categories determined by the locally weighted least squares graphical method applied to the logit of the mortality and by univariate logistic regressions for reducing candidates for the score. Multivariate logistic regression was used to construct the final score. Cutoff values for 99.5% specificity were determined. Of 6796 patients, 5602 were admitted and 1194 rejected. The initial refusal score included age, diagnosis, systolic blood pressure, pulse, respirations, creatinine, bilirubin, PaO2, bicarbonate, albumin, use of vasopressors, Glasgow Coma Scale score, Karnofsky Scale, operative status and chronic disorder, and the initial refusal receiver operating characteristics were area under the curve 0.77 (95% confidence interval 0.76-0.79). The final triage score included age, diagnosis, creatinine, white blood cells, platelets, albumin, use of vasopressors, Glasgow Coma Scale score, Karnofsky Scale, operative status and chronic disorder, and the final score receiver operating characteristics were area under the curve 0.83 (95% confidence interval 0.80-0.86). Patients with initial refusal scores >173.5 or final triage scores = 0 should be rejected. CONCLUSIONS: The initial refusal score and final triage score provide objective data for rejecting patients that will die even if admitted to the intensive care unit and survive if refused intensive care unit admission.

The Eldicus prospective, observational study of triage decision making in European intensive care units. Part II: intensive care benefit for the elderly.

RATIONALE: Life and death triage decisions are made daily by intensive care unit physicians. Admission to an intensive care unit is denied when intensive care unit resources are constrained, especially for the elderly. OBJECTIVE: To determine the effect of intensive care unit triage decisions on mortality and intensive care unit benefit, specifically for elderly patients. DESIGN: Prospective, observational study of triage decisions from September 2003 until March 2005. SETTING: Eleven intensive care units in seven European countries. PATIENTS: All patients >18 yrs with an explicit request for intensive care unit admission. INTERVENTIONS: Admission or rejection to intensive care unit. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, hospital, physiologic variables, and 28-day mortality were obtained on consecutive patients. There were 8,472 triages in 6,796 patients, 5,602 (82%) were accepted to the intensive care unit, 1,194 (18%) rejected; 3,795 (49%) were ≥ 65 yrs. Refusal rate increased with increasing patient age (18-44: 11%; 45-64: 15%; 65-74: 18%; 75-84: 23%; >84: 36%). Mortality was higher for older patients (18-44: 11%; 45-64: 21%; 65-74: 29%; 75-84: 37%; >84: 48%). Differences between mortalities of accepted vs. rejected patients, however, were greatest for older patients (18-44: 10.2% vs. 12.5%; 45-64: 21.2% vs. 22.3%; 65-74: 27.9% vs. 34.6%; 75-84: 35.5% vs. 40.4%; >84: 41.5% vs. 58.5%). Logistic regression showed a greater mortality reduction for accepted vs. rejected patients corrected for disease severity for elderly patients (age >65 [odds ratio 0.65, 95% confidence interval 0.55-0.78, p < .0001]) than younger patients (age <65 [odds ratio 0.74, 95% confidence interval 0.57-0.97, p = .01]). CONCLUSIONS: Despite the fact that elderly patients have more intensive care unit rejections than younger patients and have a higher mortality when admitted, the mortality benefit appears greater for the elderly. Physicians should consider changing their intensive care unit triage practices for the elderly.

Patterns of adult tobacco use in Uzbekistan.

BACKGROUND: Little is known about the prevalence of tobacco use in Uzbekistan, a country targeted intensively by the international tobacco industry. METHODS: A national household survey elicited information about cigarette smoking and nasway use (a form of smokeless tobacco). RESULTS: Prevalence of past-month smoking and nasway use among men (N=1795) was 19.6% and 22.3%, respectively, and 1.6% and 0.5% among women (N=1831). Among men, smoking was independently associated with Uzbek ethnicity, urban residence, age and occupation; nasway use was associated with rural residence, age, being married and occupation. CONCLUSIONS: The smoking rate in Uzbekistan remains low relative to neighbouring countries, perhaps due to widespread use of cheaper nasway. These findings establish a baseline for future surveys and highlight the importance of smokeless tobacco in assessing overall consumption.

Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study.

OBJECTIVE: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV). METHODS: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months. RESULTS: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02) and gastrointestinal toxicity with 5FU+LV (p=0.03). Female patients treated with 5FU+LEV had improved overall survival. CONCLUSIONS: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

Implications of ICU triage decisions on patient mortality: a cost-effectiveness analysis.

INTRODUCTION: Intensive care is generally regarded as expensive, and as a result beds are limited. This has raised serious questions about rationing when there are insufficient beds for all those referred. However, the evidence for the cost effectiveness of intensive care is weak and the work that does exist usually assumes that those who are not admitted do not survive, which is not always the case. Randomised studies of the effectiveness of intensive care are difficult to justify on ethical grounds; therefore, this observational study examined the cost effectiveness of ICU admission by comparing patients who were accepted into ICU after ICU triage to those who were not accepted, while attempting to adjust such comparison for confounding factors. METHODS: This multi-centre observational cohort study involved 11 hospitals in 7 EU countries and was designed to assess the cost effectiveness of admission to intensive care after ICU triage. A total of 7,659 consecutive patients referred to the intensive care unit (ICU) were divided into those accepted for admission and those not accepted. The two groups were compared in terms of cost and mortality using multilevel regression models to account for differences across centres, and after adjusting for age, Karnofsky score and indication for ICU admission. The analyses were also stratified by categories of Simplified Acute Physiology Score (SAPS) II predicted mortality (< 5%, 5% to 40% and >40%). Cost effectiveness was evaluated as cost per life saved and cost per life-year saved. RESULTS: Admission to ICU produced a relative reduction in mortality risk, expressed as odds ratio, of 0.70 (0.52 to 0.94) at 28 days. When stratified by predicted mortality, the odds ratio was 1.49 (0.79 to 2.81), 0.7 (0.51 to 0.97) and 0.55 (0.37 to 0.83) for <5%, 5% to 40% and >40% predicted mortality, respectively. Average cost per life saved for all patients was $103,771 (€82,358) and cost per life-year saved was $7,065 (€5,607). These figures decreased substantially for patients with predicted mortality higher than 40%, $60,046 (€47,656) and $4,088 (€3,244), respectively. Results were very similar when considering three-month mortality. Sensitivity analyses performed to assess the robustness of the results provided findings similar to the main analyses. CONCLUSIONS: Not only does ICU appear to produce an improvement in survival, but the cost per life saved falls for patients with greater severity of illness. This suggests that intensive care is similarly cost effective to other therapies that are generally regarded as essential.

Calcification in retinoblastoma: histopathologic findings and statistical analysis of 302 cases.

AIM: To evaluate the histopathologic factors statistically associated with the presence of calcification in eyes with retinoblastoma. METHODS: Retrospective, consecutive and observational case series. Three hundred and two enucleated eyes with retinoblastoma examined between the years 1960 and 2008. Five representative histopathologic slides of the pupil-optic nerve section and three cross optic nerve sections were retrospectively reviewed. The presence and degree of calcification as well as other histopathologic features were evaluated. Demographic data including age, gender and country of origin of the case were also reviewed. Univariate and multivariate statistical analyses were performed to search for a possible correlation between calcification and the other histopathologic factors and/or demographic data. RESULTS: Calcification was present in 84.9% of cases. Age, tumour size, necrosis, basophilic staining, iris neovascularisation, choroidal, scleral and/or optic nerve invasion were correlated significantly with calcification. Multivariate analysis showed a significant correlation between the presence of calcification and the amount of necrosis and choroidal invasion only. CONCLUSIONS: In this series, calcification was more frequent in cases with more necrosis and cases with choroidal invasion, a known poor histopathologic risk factor for metastatic disease. The possible clinical implication of the findings from this study deserves additional studies.

Reasons for refusal of admission to intensive care and impact on mortality.

PURPOSE: To identify factors influencing triage decisions and investigate whether admission to the intensive care unit (ICU) could reduce mortality compared with treatment on the ward. METHODS: A multicentre cohort study in 11 university hospitals from seven countries, evaluating triage decisions and outcomes of patients referred for admission to ICU who were either accepted, or refused and treated on the ward. Confounding in the estimation of the effect of ICU admission on mortality was controlled by use of a propensity score approach, which adjusted for the probability of being admitted. Variability across centres was accounted for in both analyses of factors influencing ICU admission and effect of ICU admission on mortality. RESULTS: Eligible were 8,616 triages in 7,877 patients referred for ICU admission. Variables positively associated with probability of being admitted to ICU included: ventilators in ward; bed availability; Karnofsky score; absence of comorbidity; presence of haematological malignancy; emergency surgery and elective surgery (versus medical treatment); trauma, vascular involvement, liver involvement; acute physiologic score II; ICU treatment (versus ICU observation). Multiple triages during patient's hospital stay and age were negatively associated with ICU admission. The area under the receiver operating characteristic (ROC) curve of the model was 0.83 [95% confidence interval (CI): 0.81-0.84], with Hosmer-Lemeshow test P = 0.300. ICU admission was associated with a statistically significant reduction of both 28-day mortality [odds ratio (OR): 0.73; 95% CI: 0.62-0.87] and 90-day mortality (0.79; 0.66-0.93). The benefit of ICU admission increased substantially in patients with greater severity of illness. CONCLUSIONS: We suggest that intensivists take great care to avoid ICU admission of patients judged not severe enough for ICU or with low performance status, and they tend to admit surgical patients more readily than medical patients. Interestingly, they do not judge age per se as a reason for refusal of ICU admission. Admission to ICU was associated with a reduction of both 28- and 90-day mortality, particularly in patients with greater severity of illness at time of triage.

Relieving suffering or intentionally hastening death: where do you draw the line?

OBJECTIVE: End-of-life practices vary worldwide. The objective was to demonstrate that there is no clear-cut distinction between treatments administered to relieve pain and suffering and those intended to shorten the dying process. DESIGN: Secondary analysis of a prospective, observational study. SETTING: Thirty-seven intensive care units in 17 European countries. PATIENTS: Consecutive patients dying or with any limitation of therapy. INTERVENTIONS: Evaluation of the type of end-of-life category; dates and times of intensive care unit admission, death, or discharge; and decisions to limit therapy, medication, and doses used for active shortening of the dying process and the intent of the doctors prescribing the medication. MEASUREMENTS AND MAIN RESULTS: Limitation of life-sustaining therapy occurred in 3,086 (72.6%) of 4,248 patients, and 94 (2.2%) underwent active shortening of the dying process. Medication for active shortening of the dying process included administration of opiates (morphine to 71 patients) or benzodiazepines (diazepam to 54 patients) alone or in combination. The median dosage for morphine was 25.0 mg/hr and for diazepam 20.8 mg/hr. Doses of opiates and benzodiazepines were no higher than mean doses used with withdrawal in previous studies in 20 of 66 patients and were within the ranges of doses used in all but one patient. Doctors considered that medications for active shortening of the dying process definitely led to the patient's death in 72 patients (77%), probably led to the patient's death in 11 (12%), and were unlikely to have led to death in 11 (12%) patients. CONCLUSIONS: There is a gray area in end-of-life care between treatments administered to relieve pain and suffering and those intended to shorten the dying process.

Reasons, considerations, difficulties and documentation of end-of-life decisions in European intensive care units: the ETHICUS Study.

OBJECTIVE: To evaluate physicians' reasoning, considerations and possible difficulties in end-of-life decision-making for patients in European intensive care units (ICUs). DESIGN: A prospective observational study. SETTING: Thirty-seven ICUs in 17 European countries. PATIENTS AND PARTICIPANTS: A total of 3,086 patients for whom an end-of-life decision was taken between January 1999 and June 2000. The dataset excludes patients who died after attempts at cardiopulmonary resuscitation and brain-dead patients. MEASUREMENTS AND RESULTS: Physicians indicated which of a pre-determined set of reasons for, considerations in, and difficulties with end-of-life decision-making was germane in each case as it arose. Overall, 2,134 (69%) of the decisions were documented in the medical record, with inter-regional differences in documentation practice. Primary reasons given by physicians for the decision mostly concerned the patient's medical condition (79%), especially unresponsive to therapy (46%), while chronic disease (12%), quality of life (4%), age (2%) and patient or family request (2%) were infrequent. Good medical practice (66%) and best interests (29%) were the commonest primary considerations reported, while resource allocation issues such as cost effectiveness (1%) and need for an ICU bed (0%) were uncommon. Living wills were considered in only 1% of cases. Physicians in central Europe reported no significant difficulty in 81% of cases, while in northern and southern regions there was no difficulty in 92-93% of cases. CONCLUSIONS: European ICU physicians do not experience difficulties with end-of-life decisions in most cases. Allocation of limited resources is a minor consideration and autonomous choices by patient or family remain unusual. Inter-regional differences were found.

Trabecular bone gradient in rat long bone metaphyses: mathematical modeling and application to morphometric measurements and correction of implant positioning.

UNLABELLED: The distribution of trabecular structures in mammalian long bone metaphyses has been insufficiently explored. We show in rats that the trabecular bone structural parameters display a decreasing gradient, toward the diaphysis, that can be defined mathematically. This gradient is applicable for optimizing the reference volume in metabolic studies and for retrospective correction of implant positioning. INTRODUCTION: The mammalian metaphyseal trabecular bone is unevenly distributed. Hence, defining a standard reference volume is critical for morphometric analyses in metaphyseal sites. MATERIALS AND METHODS: The distal femoral and proximal tibial metaphyses of adult orchietomized (ORX) or sham-ORX rats were scanned by microCT 6 wk postoperatively. Morphometric analysis based on 3D image data was performed in 450-microm-thick transversal segments defined consecutively from the primary spongiosa toward the diaphysis. The results were subjected to curve-fit analysis. A similar approach was used for proximal tibial metaphyseal sites carrying titanium implants inserted horizontally 6 wk post-ORX and examined 2-12 wk after implantation. RESULTS: The respective curve-fit analysis in both femur and tibia revealed decreasing linear/quadratic and logarithmic gradients for all morphometric parameters in the sham-ORX animals. The ORX animals showed similar gradients with roughly similar slopes but lower values. For the bone volume (BV/TV) and connectivity (Conn.D) densities, the magnitude of the ORX effect vastly increased toward the diaphysis. The trabecular number was unaffected in ORX femora and tibias. The trabecular thickness showed a constant decrease in the femur and was unchanged in the tibia. These findings are useful for the determination and reporting of reference volumes in morphometric studies. Implementing the curve-fit analysis for retrospective correction of implant positioning revealed differences in BV/TV, Tb.N, Conn.D, and percent implant surface in contact with bone (%OI) between the sham-ORX and ORX rats. These differences were otherwise undisclosed. In addition, a temporal increase in %OI was shown only for the corrected measurements. CONCLUSIONS: We show the feasibility of modeling trabecular bone structures using mathematical tools. Such modeling may be used as an experimental tool. Moreover, if proven applicable to human skeletal structures, it may be further developed for the diagnosis of metabolic bone diseases and evaluation of therapeutic measures.

The importance of religious affiliation and culture on end-of-life decisions in European intensive care units.

OBJECTIVE: To determine the influence of religious affiliation and culture on end-of-life decisions in European intensive care units (ICUs). DESIGN AND SETTING: A prospective, observational study of European ICUs was performed on consecutive patients with any limitation of therapy. Prospectively defined end-of-life practices in 37 ICUs in 17 European countries studied from 1 January 1999 to 30 June 2000 were compared for frequencies, patterns, timing, and communication by religious affiliation of physicians and patients and regions. RESULTS: Of the 31,417 patients 3,086 had limitations. Withholding occurred more often than withdrawing if the physician was Jewish (81%), Greek Orthodox (78%), or Moslem (63%). Withdrawing occurred more often for physicians who were Catholic (53%), Protestant (49%), or had no religious affiliation (47%). End-of-life decisions differed for physicians between regions and who had any religious affiliation vs. no religious affiliation in all three geographical regions. Median time from ICU admission to first limitation of therapy was 3.2 days but varied by religious affiliation; from 1.6 days for Protestant to 7.6 days for Greek Orthodox physicians. Median times from limitations to death also varied by physician's religious affiliation. Decisions were discussed with the families more often if the physician was Protestant (80%), Catholic (70%), had no religious affiliation (66%) or was Jewish (63%). CONCLUSIONS: Significant differences associated with religious affiliation and culture were observed for the type of end of life decision, the times to therapy limitation and death, and discussion of decisions with patient families.

Attitudes of European physicians, nurses, patients, and families regarding end-of-life decisions: the ETHICATT study.

OBJECTIVE: To evaluate attitudes of Europeans regarding end-of-life decisions. DESIGN AND SETTING: Responses to a questionnaire by physicians and nurses working in ICUs, patients who survived ICU, and families of ICU patients in six European countries were compared for attitudes regarding quality and value of life, ICU treatments, active euthanasia, and place of treatment. MEASUREMENTS AND RESULTS: Questionnaires were distributed to 4,389 individuals and completed by 1,899 (43%). Physicians (88%) and nurses (87%) found quality of life more important and value of life less important in their decisions for themselves than patients (51%) and families (63%). If diagnosed with a terminal illness, health professionals wanted fewer ICU admissions, uses of CPR, and ventilators (21%, 8%, 10%, respectively) than patients and families (58%, 49%, 44%, respectively). More physicians (79%) and nurses (61%) than patients (58%) and families (48%) preferred being home or in a hospice if they had a terminal illness with only a short time to live. CONCLUSIONS: Quality of life was more important for physicians and nurses than patients and families. More medical professionals want fewer ICU treatments and prefer being home or in a hospice for a terminal illness than patients and families.

Neonatal transport of very low birth weight infants in Jerusalem, revisited.

BACKGROUND: Maternal transport, rather than neonatal transport, to tertiary care centers is generally advocated. Since a substantial number of premature deliveries still occur in hospitals with level I and level II nurseries, it is imperative to find means to improve their outcome. OBJECTIVES: To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very low birth weight infants, accounting for sociodemographic, obstetric and perinatal variables, with reference to earlier published data. METHODS: We compared 129 premature infants with birth weights of 750-1250 g delivered between 1996 and 2000 in a hospital providing neonatal intensive care to 99 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistical significant association with the outcome variables and dissimilar distribution in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression. RESULTS: Accounting for the covariates, the odds ratios (outborns relative to inborns) were 0.31 (95% confidence interval = 0.11-0.86, P = 0.03) for mortality, 1.37 (95% CI = 0.64-2.96, P = 0.42) for severe intraventricular hemorrhage, and 0.86 (95% CI = 0.38-1.97, P = 0.78) for bronchopulmonary dysplasia. The odds ratio for survival without severe intraventricular hemorrhage was 1.10 (95% CI = 0.55-2.20, P = 0.78). Comparing the current results with earlier (1990-94) published data from the same institution showed that mortality decreased in both the outborn and inborn infants (OR = 0.23, 95% CI = 0.09-0.58, P = 0.002 and 0.46; 95% CI = 0.20-1.04, P = 0.06, respectively), but no significant change in the incidence of severe intraventricular hemorrhage or brochopulmonary dysplasia was observed. Increased survival was observed also in these infants receiving surfactant, more so among the outborn. The latter finding could be attributed to the early, pre-transport surfactant administration, implemented only in the current study. CONCLUSIONS: Our data suggest that very low birth weight outborn infants may share an outcome comparable with that of inborn babies, if adequate perinatal care including surfactant administration is provided prior to transportation to a tertiary center.

Nurse involvement in end-of-life decision making: the ETHICUS Study.

OBJECTIVE: The purpose was to investigate physicians' perceptions of the role of European intensive care nurses in end-of-life decision making. DESIGN: This study was part of a larger study sponsored by the Ethics Section of the European Society of Intensive Care Medicine, the ETHICUS Study. Physicians described whether they thought nurses were involved in such decisions, whether nurses initiated such a discussion and whether there was agreement between physicians and nurses. The items were analyzed and comparisons were made between different regions within Europe. SETTING: The study took place in 37 intensive care units in 17 European countries. PATIENTS AND PARTICIPANTS: Physician investigators reported data related to patients from 37 centers in 17 European countries. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Physicians perceived nurses as involved in 2,412 (78.3%) of the 3,086 end-of-life decisions (EOLD) made. Nurses were thought to initiate the discussion in 66 cases (2.1%), while ICU physicians were cited in 2,438 cases (79.3%), the primary physician in 328 cases (10.7%), the consulting physician in 105 cases (3.4%), the family in 119 cases (3.9%) and the patient in 19 cases (0.6%). In only 20 responses (0.6%) did physicians report disagreement between physicians and nurses related to EOLD. A significant association was found between the region and responses to the items related to nursing. Physicians in more northern regions reported more nurse involvement. CONCLUSIONS: Physicians perceive nurses as involved to a large extent in EOLDs, but not as initiating the discussion. Once a decision is made, there is a sense of agreement. The level of perceived participation is different for different regions.