Validation of the type 1 diabetes distress scale (T1-DDS) in a large Danish cohort: Content validation and psychometric properties.

Aim: To validate the Type 1 Diabetes Distress Scale (T1-DDS) in a large sample of adults with Type 1 diabetes (T1D) from diabetes clinics in Denmark. Methods: Altogether 40 adults with T1D were interviewed to explore the content of T1-DDS in a Danish setting and to validate the translation of the T1-DDS into Danish. Subsequently, a survey including T1-DDS, the Problem Areas In Diabetes scale (PAID-20), fear of hypoglycemia, social support, and diabetes duration was answered by 2201 people with T1D. Other person characteristics were collected from the National Patient Register. HbA1c was obtained from the Clinical Laboratory Information System. Data distribution, internal consistency, convergent and construct validity, factor structure, three weeks retest, and cut-points were explored. Results: Interview data supported the relevance of all T1-DDS items for the assessment of diabetes distress among adults with T1D. The T1-DDS showed good content and acceptable construct validity, and the ability to detect high diabetes distress levels. A high correlation between T1-DDS and PAID-20 (rho = 0.91) was found. The retest scores showed a good reliability (all rho ≥0.68) with the highest variability in the Friends/Family Distress and Physician Distress subscales and the lowest variability in the Powerlessness and Eating Distress subscales of the T1-DDS. Qualitative findings pointed out relevant concerns of people with T1D, which were not included in the T1-DDS. Conclusion: The study supports the use of the Danish T1-DDS, but also highlights that existing diabetes distress questionnaires including T1-DDS do not cover all potential diabetes stressors and worries.

A new perspective on diabetes distress using the type 2 diabetes distress assessment system (T2-DDAS): Prevalence and change over time.

AIMS: To establish cut-points and thresholds for elevated diabetes distress; document change over time; and define minimal clinically important differences (MCID) using the new Type 2 Diabetes Distress Assessment System (T2-DDAS). METHODS: A national sample of adults with type 2 diabetes completed the T2-DDAS CORE distress scale and the 7 T2-DDAS SOURCE distress scales at baseline and 6-months. Scores were computed separately for insulin- and non-insulin users. Spline regression models defined CORE cut-points and SEM formulas defined MCID. A rational "threshold" approach defined elevated SOURCE scores. RESULTS: 471 participants (205 insulin, 266 non-insulin) completed both assessments. Analyses yielded ≥2.0 as the cut-point for both elevated CORE and elevated SOURCE. Prevalence of elevated CORE was 61.8 % (69.9 % over 6 months). Elevated SOURCE scores varied from 30.6 % (Stigma/Shame) to 76.4 % (Management); 87.5 % indicated at least 1 elevated SOURCE score. Most (77.1 %) reported multiple elevated SOURCES. 81.8 % with elevated CORE distress at baseline remained elevated at 6 months. MCID analyses yielded +/- 0.25 as significant change. Few differences between insulin- and non-insulin users occurred. CONCLUSIONS: Elevated CORE distress is highly prevalent and persistent over time; most participants reported multiple SOURCES of distress. Findings highlight the need for comprehensive assessment of diabetes distress.

Worries and concerns about hypoglycemia in adults with type 1 diabetes: An examination of the reliability and validity of the Hypoglycemic Attitudes and Behavior Scale (HABS).

AIMS: To examine the factor structure, validity and reliability of the Hypoglycemic Attitudes and Behavior Scale (HABS) in T1D adults (previously examined only in T2D adults), and to determine if it has unique value, after controlling for hypoglycemic fear. METHODS: The original 14 HABS items were submitted to a confirmatory factor analysis (CFA) with T1D participants. Construct validity criteria included diabetes distress, generalized anxiety, well-being, hypoglycemic fear, hypoglycemia history and self-reported glycemic control. RESULTS: A CFA yielded a similar 3-factor solution, with all items loading on the same factors as in the analyses with T2D adults: Hypoglycemia Anxiety, Avoidance and Confidence. Higher levels of Anxiety and Avoidance were significantly associated with poorer well-being and higher levels of generalized anxiety, diabetes distress and hypoglycemic fear, with correlations in the reverse direction for Confidence. After controls (including hypoglycemic fear), the HABS subscales were significantly linked to several criterion variables. CONCLUSIONS: Though originally developed and validated with T2D adults, the HABS demonstrates sufficient validity and reliability for use with a T1D population; and it captures unique critical elements of hypoglycemic concerns. Thus, it may contribute to a greater understanding of hypoglycemia management and more targeted clinical interventions in a T1D population.

There is value in treating elevated levels of diabetes distress: the clinical impact of targeted interventions in adults with Type 1 diabetes.

AIM: To compare the effect of targeted interventions to reduce high diabetes distress among adults with Type 1 diabetes with a comparison sample of similar but untreated individuals, and to document the stability of untreated diabetes distress over time. METHODS: A total of 51 adults with Type 1 diabetes with elevated baseline diabetes distress (distress score ≥ 2.0) and HbA1c levels (≥ 58 mmol/mol) were identified from a longitudinal, non-intervention study, and compared with a similar sample of 51 participants in an intervention study. Both groups completed the T1-DDS diabetes distress questionnaire at baseline and 9 months. RESULTS: Large and significant reductions in diabetes distress scores were recorded in the intervention group (mean ± sd change = -0.6 ± 0.6), while minimal change was found in the non-intervention group (-0.2 ± 0.6, group effect P = 0.002; effect size d = 0.67). Additional analyses using the established minimal clinically important difference for the T1-DDS showed that diabetes distress increased significantly (minimal clinically important difference ≥ 1) or persisted at high levels for 51% of participants in the non-intervention group, compared with 23.5% in the intervention group. CONCLUSION: Our results showed that targeted interventions led to dramatic reductions in diabetes distress compared with a lack of treatment. We also conclude that elevated diabetes distress, when left unaddressed, does not resolve over time and often remains chronic. (Clinical Trials Registry no.: NCT02175732).

Descriptions of diabetes burnout from individuals with Type 1 diabetes: an analysis of YouTube videos.

AIM: The purpose of the study was to analyse self-descriptions of diabetes burnout in individuals with Type 1 diabetes via YouTube videos. METHODS: In this qualitative descriptive study, a systematic approach was used to search YouTube videos with a title, description or content specifically about diabetes burnout dated between 2007 and 2017. Irrelevant or duplicated videos were excluded using eligibility criteria. All videos meeting inclusion criteria (n = 32) from individuals with Type 1 diabetes were transcribed verbatim and analysed using a qualitative content analysis approach. Descriptive statistics were used to analyse video characteristics. RESULTS: The four major themes associated with diabetes burnout were: (i) feeling mentally drained and physically tired of dealing with self-care; (ii) experiencing a detachment from self, diabetes care and support system; (iii) being powerless and paralysed to 'climb out' of diabetes burnout; and (iv) contributing potential factors to diabetes burnout. CONCLUSIONS: Self-descriptions of diabetes burnout suggest that it is a combination of emotions and behaviours on a spectrum from exhaustion to detachment accompanied by an overwhelming sense of powerlessness. More studies are needed to further clarify diabetes burnout and its distinction from, or overlap with, other related psychosocial concepts in diabetes care.

Can the Routine Use of Patient-Reported Outcome Measures Improve the Delivery of Person-Centered Diabetes Care? A Review of Recent Developments and a Case Study.

PURPOSE OF REVIEW: In recent years, the recommendation for and use of patient-reported outcome measures (PROMs) in routine diabetes care has significantly increased. We review recent evidence and highlight key opportunities and challenges related to the active clinical use of PROMs to support person-centered diabetes care and focus areas for future research in the area. RECENT FINDINGS: Recent pragmatic studies support that integration of multi-dimensional PROMs for diabetes in clinical care as part of a care improvement strategy can be acceptable for and valued by people with diabetes (PWD) and healthcare professionals (HCPs) and may improve multiple aspects of quality of care, including screening, medical care monitoring and decision support, individualization of self-management support and goal-setting, and broader benefits related to active patient participation and person-centred diabetes care. We identify multiple intervention, individual, and care setting characteristics, which influence acceptability, feasibility, implementation, and effectiveness of PROMs in routine care. Recent clinical PROM studies highlight the value of mixed methods research and systematic involvement of PWD, clinicians, and other stakeholders in the design and implementation of questionnaires for patient input in routine diabetes care. We identified a new significant trend towards participatory development of multi-dimensional PROMs with the aim of IT-enabled integration into routine diabetes care to facilitate multiple components of person-centered diabetes care and better clinical, quality of life, and cost outcomes. While results from large-scale randomized controlled studies are still limited, a growing number of pragmatic implementation studies support that user-centric PROM interventions have the potential to facilitate significant improvements in care for PWD.

Addressing diabetes distress in clinical care: a practical guide.

Addressing the emotional side of diabetes and its management has received considerable attention in recent years. At the centre of most of these efforts is the concept of 'diabetes distress', a generic term that captures the primary sources and intensity of emotional distress associated with diabetes and its management over time. As interest in diabetes distress has grown, however, it has been difficult to integrate and translate the various strands of clinical research in a manner that can guide diabetes distress intervention efforts in the real world of clinical care. The aim of this paper is to fill this gap by outlining practical strategies for intervention in clinical settings and to assist diabetes healthcare professionals in thinking through how diabetes distress might be addressed practically in their clinics. To address these goals, this review is divided into five sections: a definition of diabetes distress, ways diabetes distress can be assessed and monitored, information about diabetes distress for use in intervention planning, topics to be considered for inclusion in diabetes distress interventions, and alternatives for where in the care process a diabetes distress intervention might be considered. We focus on diabetes distress experienced by adults with both Type 1 and Type 2 diabetes.

Two for one? Effects of a couples intervention on partners of persons with Type 2 diabetes: a randomized controlled trial.

AIMS: To compare the outcomes of partners who participated in a telephone couples behavioural intervention to improve glycaemic control in persons with Type 2 diabetes with those of untreated partners of participants in an individual intervention or education; to explore 'ripple effects', i.e. positive behaviour changes seen in untreated partners. METHODS: The Diabetes Support Project was a three-arm randomized telephone intervention trial comparing outcomes of couples calls (CC), individual calls (IC) and diabetes education calls (DE). Couples included one partner with Type 2 diabetes and HbA1c ≥ 58 mmol/mol (7.5%). All arms received self-management education (two calls). CC and IC arms participated in 10 additional behaviour change calls. CC included partners, emphasizing partner communication, collaboration and support. Blinded assessments were performed at 4, 8 and 12 months. Partner outcomes were psychosocial (diabetes distress, relationship satisfaction, depressive symptoms), medical (BMI, blood pressure) and behavioural (fat intake, activity). RESULTS: Partners' (N = 268) mean age was 55.8 years, 64.6% were female and 29.9% were from minority ethnic groups. CC (vs. IC and DE) partners had greater reductions in diabetes distress, greater increases in marital satisfaction (4 and 8 months), and some improvements in diastolic BP. There were no consistent differences among arms in other outcomes. There was no evidence of a dietary or activity behaviour ripple effect on untreated partners, i.e. comparing partners in the IC and DE arms. CONCLUSIONS: A collaborative couples intervention resulted in significant improvements in partner diabetes distress and relationship satisfaction. There were no consistent effects on behavioural or medical partner outcomes, and no evidence of diet or activity behaviour ripple effects, suggesting that partners should be targeted directly to achieve these changes. (Clinical Trial Registry No: NCT01017523).

The impact of non-severe hypoglycemia on quality of life in patients with type 2 diabetes.

AIMS: To determine the impact of frequency of non-severe hypoglycemic events (NSHE) and the perceived burden of NSHE on quality of life (QOL) over time. METHODS: T2D adults (n = 424) were re-contacted two years after initial QOL assessment. Responding subjects (n = 290) reported the frequency and burden of NSHE over time and completed six generic and diabetes-specific QOL measures. RESULTS: Most subjects (86%) reported ≥ one NSHE over time. Higher frequency of NSHE was significantly associated with decrements in QOL. Greater perceived burden of NSHE was significantly linked to decreases in QOL over time for all six QOL measures. Interaction terms indicated that participants with a higher frequency of NSHE and higher perceived burden reported the greatest decrease in QOL; participants who experienced frequent NSHE but did not perceive these events as burdensome evidenced little worsening in QOL over time. CONCLUSIONS: NSHE have a negative impact on QOL over time in T2D adults. However, it is not just the occurrence of NSHE that affects QOL; it is the individual's felt burden of these events that is critical. The greatest reductions in QOL are seen among those subjects reporting a higher frequency of NSHE and indicating that such events are burdensome.

A practical framework for encouraging and supporting positive behaviour change in diabetes.

A wide range of diabetes-directed interventions - including novel medications, devices and comprehensive education programmes - have been shown to be effective in clinical trials. But in the real world of diabetes care their efficacy is often dependent upon on how well a clinician is able to support personal engagement and motivation of the person with diabetes to use these new tools and knowledge consistently, and as directed. Although many person-centred motivational and behavioural strategies have been developed, for example, action planning, motivational interviewing and empowerment-based communication, the sheer number and apparent lack of clear differences among them have led to considerable confusion. The primary goal of this review, therefore, is to provide a practical framework that organizes and structures these programmes to enhance their more systematic use in clinical care. Its purpose is to enhance clinician efforts to respectfully encourage and support engagement and motivation for behaviour change in people with diabetes. The three-step framework for organizing and describing the specific clinical processes involved is based on self-determination theory and includes: clinician preparation for a different type of clinical encounter, clinician/person with diabetes relationship building, and clinician utilization of specific behavioural tools. We conclude with practical considerations for application of this framework to the real world of clinical care.

Diabetes distress is linked with worsening diabetes management over time in adults with Type 1 diabetes.

AIM: To determine the cross-sectional and longitudinal associations between diabetes distress and diabetes management. METHODS: In a non-interventional study, 224 adults with Type 1 diabetes were assessed for diabetes distress, missed insulin boluses, hypoglycaemic episodes, and HbA1c at baseline and 9 months. RESULTS: At baseline, greater distress was associated with higher HbA1c and a greater percentage of missed insulin boluses. Longitudinally, elevated baseline distress was related to increased missed insulin boluses, and decreases in distress were associated with decreases in HbA1c . In supplementary analyses, neither depression symptoms nor a diagnosis of major depressive disorder was associated with missed insulin boluses, HbA1c or hypoglycaemic episodes in cross-sectional or longitudinal analyses. CONCLUSIONS: Significant cross-sectional and longitudinal associations were found between diabetes distress and management; in contrast, no parallel associations were found for major depressive disorder or depression symptoms. Findings suggest that elevated distress may lead to more missed insulin boluses over time, suggesting a potential intervention target. The covarying association between distress and HbA1c points to the complex and likely interactive associations between these constructs. Findings highlight the need to address distress as an integral part of diabetes management in routine care.

Prevalence of depression in Type 1 diabetes and the problem of over-diagnosis.

AIMS: To determine the prevalence of depression and diabetes distress in adults with Type 1 diabetes and the rate of false-positives when compared with rates of major depressive disorder. METHODS: The sample consisted of 368 individuals with Type 1 diabetes, aged > 19 years. Individuals completed: the eight-item Patient Health Questionnaire depression scale (PHQ8), which was coded using four scoring criteria (scores > 10, >12 and >15, and Diagnostic and Statistical Manual of Mental Disorders 5 (DSM) algorithm scores); the Type 1 Diabetes Distress Scale; and the Structured Clinical Interview for DSM Disorders (SCID) to assess major depressive disorder. RESULTS: The prevalence rates of depression according to the eight-item Patient Health Questionnaire were: score >10, 11.4%; score >12, 7.1%; score >15, 3.8%; and positive algorithm result, 4.6%. The prevalence of major depressive disorder was 3.5%; and the prevalence of at least moderate diabetes distress was 42.1%. Depending on the criterion used, the false-positive rate when using the Patient Health Questionnaire compared with the results when using the SCID varied from 52 to 71%. Of those classified as depressed on the PHQ-8 or Structured Clinical Interview for DSM Disorders, between 92.3 and 96.2% also reported elevated diabetes distress. No significant association was found between any group classed as having depression according to the PHQ8 or the SCID and HbA1c concentration. Depression was significantly associated with more other life stress, more complications and a lower level of education. CONCLUSIONS: We found an unexpectedly low rate of current depression and major depressive disorder in this diverse sample of adults with Type 1 diabetes, and a very high rate of false-positive results using the Patient Health Questionnaire. Considering the high prevalence of diabetes distress, much of what has been considered depression in adults with Type 1 diabetes may be attributed to the emotional distress associated with managing a demanding chronic disease and other life stressors and not necessarily to underlying psychopathology.

Identifying the worries and concerns about hypoglycemia in adults with type 2 diabetes.

AIMS: To identify the hypoglycemic concerns of adults with type 2 diabetes (T2D) and examine how these concerns are associated with key patient characteristics. METHODS: Qualitative interviews with 16 T2D adults and 11 diabetes care providers were conducted. Survey items were then developed and submitted to exploratory factor analyses (EFAs). Construct validity was assessed by correlations with diabetes distress, anxiety and depressive symptoms, well-being, hypoglycemic fear, hypoglycemia history and glycemic control (A1C). RESULTS: An EFA with 226 insulin users and 198 non-insulin users yielded 3 factors (14 items): Hypoglycemia Anxiety, Avoidance and Confidence. For both T2D groups, higher Anxiety and Avoidance were significantly associated with more hypoglycemia, lower well-being, and greater diabetes distress, depressive symptoms and hypoglycemic fear. Similar associations, in the converse direction, were found for Confidence. Among insulin users only, Anxiety was independently associated with greater emotional distress and more hypoglycemia, while Confidence was independently linked to less emotional distress and lower A1C. Avoidance was independently associated with greater emotional distress in both groups. CONCLUSIONS: Using the new 14-item Hypoglycemic Attitudes and Behavior Scale (HABS), we found that hypoglycemic concerns are significant in T2D adults, are linked to emotional distress and A1C, and merit attention in clinical practice.

Impact of baseline patient characteristics on interventions to reduce diabetes distress: the role of personal conscientiousness and diabetes self-efficacy.

AIMS: To improve patient-centred care by determining the impact of baseline levels of conscientiousness and diabetes self-efficacy on the outcomes of efficacious interventions to reduce diabetes distress and improve disease management. METHODS: Adults with Type 2 diabetes with diabetes distress and self-care problems (N = 392) were randomized to one of three distress reduction interventions: computer-assisted self-management; computer-assisted self-management plus problem-solving therapy; and health education. The baseline assessment included conscientiousness and self-efficacy, demographics, diabetes status, regimen distress, emotional burden, medication adherence, diet and physical activity. Changes in regimen distress, emotional burden and self-care between baseline and 12 months were recorded and ancova models assessed how conscientiousness and self-efficacy qualified the significant improvements in distress and management outcomes. RESULTS: Participants with high baseline conscientiousness displayed significantly larger improvements in medication adherence and emotional burden than participants with low baseline conscientiousness. Participants with high baseline self-efficacy showed greater improvements in diet, physical activity and regimen distress than participants with low baseline self-efficacy. The impact of conscientiousness and self-efficacy were independent of each other and occurred across all three intervention groups. A significant interaction indicated that those with both high self-efficacy and high conscientiousness at baseline had the biggest improvement in physical activity by 12 months. CONCLUSIONS: Both broad personal traits and disease-specific expectations qualify the outcomes of efficacious interventions. These findings reinforce the need to change from a one-size-fits-all approach to diabetes interventions to an approach that crafts clinical interventions in ways that fit the personal traits and skills of individual people.

What is so tough about self-monitoring of blood glucose? Perceived obstacles among patients with Type 2 diabetes.

AIMS: To identify patient-reported obstacles to self-monitoring of blood glucose among those with Type 2, both insulin users and non-insulin users, and to investigate how obstacles are associated with frequency of self-monitoring and use of self-monitoring data. METHODS: Patients with Type 2 diabetes (n = 886, 65% insulin users) who attended a 1-day diabetes education conference in cities across the USA completed a survey on current and recommended self-monitoring of blood glucose frequency, how they used self-monitoring results and perceived obstacles to self-monitoring use. Exploratory factor analysis examined 12 obstacle items to identify underlying factors. Regression analyses examined associations between self-monitoring of blood glucose use and the key obstacle factors identified in the exploratory factor analysis. RESULTS: Three obstacle factors emerged: Avoidance, Pointlessness and Burden. Avoidance was the only significant independent predictor of self-monitoring frequency (ß = -0.23, P < 0.001). Avoidance (ß = -0.12, P < 0.01) and Pointlessness (ß = -0.15, P < 0.001) independently predicted how often self-monitoring data were shared with healthcare professionals and whether or not data were used to make management adjustments (Avoidance: odds ratio = 0.74, P < 0.001; Pointlessness: odds ratio = 0.75, P < 0.01). Burden was not associated with any of the self-monitoring behavioural measures. Few differences between insulin users and non-insulin users were noted. CONCLUSIONS: Obstacles to self-monitoring of blood glucose use, both practical and emotional, were common. Higher levels of Avoidance and Pointlessness, but not Burden, were associated with less frequent self-monitoring use. Addressing patients' self-monitoring-related emotional concerns (Avoidance and Pointlessness) may be more beneficial in enhancing interest and engagement with self-monitoring of blood glucose than focusing on day-to-day, behavioural issues (Burden).

Patient perspectives on once-weekly medications for diabetes.

AIM: to examine patient beliefs, preferences and concerns regarding a once-weekly (QW) glucose-lowering medication option. METHODS: a total of 1516 adults with type 2 diabetes drawn from a national Chronic Illness Panel completed an anonymous online survey that assessed perceived attributes of QW therapy, willingness to take an injectable QW medication and patient characteristics that might influence their willingness, such as current perceived glycaemic control and diabetes quality of life (DQOL). RESULTS: positive attitudes regarding QW medication were common, with current injection users significantly more likely than non-injection users to view beneficial aspects: greater convenience, better medication adherence, improved quality of life (QOL) and a less overwhelming sense of treatment (in all cases, p < 0.001). In all, 46.8% reported that they would likely take an injectable QW medication if recommended by their physician, with current injection users more than twice as likely as non-injection users (73.1 vs. 31.5%; p < 0.001). Greater willingness to take QW medications was associated with poorer DQOL [injection users only; odds ratio (OR) = 1.37, p < 0.01] and poorer perceived glycaemic control (non-injection users only; OR = 1.24, p < 0.05). Concerns arose about consistency of dosage over time, potential forgetfulness and cost. CONCLUSIONS: QW glucose-lowering medications are viewed positively by patients with type 2 diabetes, especially if they are current injection users or are dissatisfied with their current treatments or outcomes. Greater convenience, better medication adherence and improved QOL are commonly endorsed attributes. Clinicians may need to review both the positive attributes of QW medications as well as common patient concerns, when considering this option.

Predicting diabetes distress in patients with Type 2 diabetes: a longitudinal study.

AIMS: Diabetes distress (DD) is a condition distinct from depression that is related to diabetes outcomes. In those without distress initially, little is known about what indicators place patients at risk for subsequent distress over time. METHODS: From a community-based, three-wave, 18-month study of Type 2 diabetic patients (n = 506), we identified patients with no DD at T1 who displayed DD at T2, T3 or both (n = 57). Using logistic regression with full and trimmed models, we compared them with patients with no DD at all three time points (n = 275) on three blocks of variables: patient characteristics (demographics, depression, extra-disease stress), biological (HbA(1c), body mass index, comorbidities, complications, blood pressure, non-high-density lipoprotein-cholesterol), and behavioural variables (diet, exercise). Selected interactions with stress and major depressive disorder (MDD) were explored. RESULTS: The odds of becoming distressed over time were higher for being female, previously having had MDD, experiencing more negative events or more chronic stress, having more complications, and having poor diet and low exercise. Negative life events increased the negative effects of both high HbA(1c) and high complications on the emergence of distress over time. CONCLUSIONS: We identified a list of significant, independent direct and interactive predictors of high DD that can be used for patient screening to identify this high-risk patient cohort. Given the impact of high DD on diabetes behavioural and biological indicators, the findings suggest the usefulness of regularly appraising both current life and disease-related stressors in clinical care.

Primary heterologous carcinosarcoma (metaplastic carcinoma) of the urinary bladder: a clinicopathologic, immunohistochemical, and ultrastructural analysis of eight cases and a review of the literature.

BACKGROUND: Heterologous carcinosarcomas of the urinary bladder are rare neoplasms, the histogenesis of which is still disputed. METHODS: The clinicopathologic, immunohistochemical, and ultrastructural features of eight cases were analyzed. RESULTS: The patients, 5 males and 3 females, had a median age of 70 years. Gross hematuria, dysuria, and urinary tract infections were the main presenting symptoms. Tumors were solitary in all cases and located in the right wall in six cases. Tumor size ranged from 2 to 12 cm (median, 5 cm). Four patients died of disease 2, 6, 17, and 42 months postoperatively, respectively. Microscopically, the tumors consisted mostly of a varied mixture of high grade transitional cell carcinoma with chondrosarcoma, osteosarcoma, rhabdomyosarcoma, and undifferentiated spindle cell (leiomyosarcoma-like) components with occasional transitional features between one component and another. All tumors but one invaded the muscularis propria or the perivesical fatty tissue. Immunohistochemically, keratin expression was observed focally in the sarcoma component as well as the carcinoma component. Reactivity for vimentin, desmin, muscle specific actin, and S-100 protein was observed in poorly differentiated areas in addition to the expected positivity of each histologic subtype of sarcoma. Ultrastructurally, one tumor showed evidence of both epithelial and chondrosarcomatous differentiation, whereas three contained rhabdomyosarcomatous elements. CONCLUSIONS: On the basis of the current series and a review of 55 reports from the literature, primary heterologous carcinosarcoma of the urinary bladder proved to be a highly malignant type of neoplasm occurring predominantly in elderly males that was most often in an advanced stage at presentation and rapidly became lethal. Histogenetically, some heterologous carcinosarcomas should be regarded as a variant of sarcomatoid carcinoma (metaplastic carcinoma) that shows prominent heterologous differentiation.

A flexible environment for the visualization of three-dimensional biological structures.

"Ducky" is a flexible and versatile software system for processing, rendering, and animating 3D datasets. The system is based on a powerful run-time interpreted language similar to C. The language includes many built-in functions for animation, rendering, shading, surface definition, and the creation of interactive menu and window-based visualization environments. Both volume and surface rendering methods are provided and may be combined in a single visualization. Ducky can create animations of a sequence of different views of a structure either within a 3D volume or across a series of volumes. Scripts implementing several common visualization tasks are provided. The system is readily extendible. Existing scripts can be modified or new scripts written to create additional interactive environments and processes.

Programs for visualization in three-dimensional microscopy.

Three-dimensional data representing biological structures can be derived using several methods, including serial section reconstruction, optical sectioning, and tomography. The investigation, comprehension, and communication of structural relationships to others is greatly facilitated by computer-based visualization procedures. We describe SYNU, a suite of programs developed for interactive investigation of three-dimensional structure and for the production of high-quality three-dimensional images and animations. We illustrate the capabilities of SYNU in applications to biological data obtained by confocal light microscopy, serial section, and high-resolution electron microscopy from investigations at the cellular, subcellular, and molecular levels.