Bridging the Age Gap: a prognostic model that predicts survival and aids in primary treatment decisions for older women with oestrogen receptor-positive early breast cancer.

BACKGROUND: A prognostic model was developed and validated using cancer registry data. This underpins an online decision support tool, informing primary treatment choice for women aged 70 years or older with hormone receptor-positive early breast cancer. METHODS: Data from women diagnosed between 2002 and 2010 in the English Northern and Yorkshire and West Midlands regions were used to develop the model. Primary treatment options of surgery with adjuvant endocrine therapy or primary endocrine therapy were compared. Models predicting the hazard of breast cancer-specific mortality and hazard of other-cause mortality were combined to derive survival probabilities. The model was validated externally using data from the Eastern Cancer Registration and Information Centre. RESULTS: The model was developed using data from 23 842 women, and validated externally on a data set from 14 526 patients. The overall model calibration was good. At 2 and 5 years, predicted mortality from breast cancer and other causes differed from the observed rate by less than 1 per cent. At 5 years, there were slight overpredictions in breast cancer mortality (2629 predicted versus 2556 observed deaths; P = 0·142) and mortality from all causes (6399 versus 6320 respectively; P = 0·583). The discrepancy varied between subgroups. Model discrimination was 0·75 or above for all mortality measures. CONCLUSION: A prognostic model for older women with oestrogen receptor-positive early breast cancer was developed and validated in the present study. This forms a basis for an online decision support tool (https://agegap.shef.ac.uk/).

ANTECEDENTES: Se ha desarrollado y validado un modelo pronóstico utilizando datos del registro de cáncer. Ello ha permitido ofrecer una herramienta online para facilitar la toma de decisiones respecto a la elección del tratamiento inicial en mujeres mayores de 70 años con cáncer de mama precoz y receptores de hormonas positivos. MÉTODOS: Se incluyeron un total de 23.842 mujeres, diagnosticadas entre 2002 y 2010 en las regiones del Norte, Yorkshire y West Midlands inglesas que cumplieron con los criterios de inclusión. Se compararon dos opciones de tratamiento: cirugía primaria asociada a tratamiento endocrino adyuvante o tratamiento primario endocrino. Para estimar la probabilidad de supervivencia se combinaron modelos predictivos para el riesgo de mortalidad específica por cáncer de mama y para el riesgo de mortalidad por otras causas. Se realizó una validación externa con datos del Eastern Cancer Registration and Information Center (n = 14.526). RESULTADOS: La calibración global del modelo fue buena. A los 2 y 5 años, la mortalidad anticipada por cáncer de mama y por otras causas difería de la observada en menos del 1%. A los 5 años, hubo una ligera sobrevaloración de la predicción de mortalidad por cáncer de mama (prevista versus real: 2.629 versus 2.556, P = 0,78) y de la mortalidad por todas las causas (6.399 versus 6.320, P = 0,14). Esta discrepancia varió entre subgrupos. La capacidad discriminativa del modelo fue del 0,75 o superior para todas las medidas de mortalidad. CONCLUSIÓN: En este estudio, se desarrolló y validó un modelo pronóstico para mujeres mayores con cáncer de mama precoz positivo para receptores de estrógenos. Esta herramienta que facilita la toma de decisiones está disponible online (https://agegap.shef.ac.uk/).

Omission of surgery in older women with early breast cancer has an adverse impact on breast cancer-specific survival.

BACKGROUND: Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer-specific survival (BCSS) in older women. METHODS: Cancer registration data for 2002-2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER)-positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation. RESULTS: Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78·5 per cent) were identified as having ER-positive disease; of these, 10 087 (53·9 per cent) had surgery and 8643 (46·1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5-year BCSS rate 69·4 and 89·9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co-morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival. CONCLUSION: BCSS in older women with ER-positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit.

Adjuvant Chemotherapy for Breast Cancer in Older Women: An Analysis of Retrospective English Cancer Registration Data.

AIMS: Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data. MATERIALS AND METHODS: Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation. RESULTS: In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67-0.81). DISCUSSION: Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference.

Looking beyond the forest: Using harvest plots, gap analysis, and expert consultations to assess effectiveness, engage stakeholders, and inform policy.

We describe a combination of methods for assessing the effectiveness of complex interventions, especially where substantial heterogeneity with regard to the population, intervention, comparison, outcomes, and study design of interest is expected. We applied these methods in a recent systematic review of the effectiveness of reinforced home-based palliative care (rHBPC) interventions, which included home-based care with an additional and explicit component of lay caregiver support. We first summarized the identified evidence, deemed inappropriate for statistical pooling, graphically by creating harvest plots. Although very useful as a tool for summary and presentation of overall effectiveness, such graphical summary approaches may obscure relevant differences between studies. Thus, we then used a gap analysis and conducted expert consultations to look beyond the aggregate level at how the identified evidence of effectiveness may be explained. The goal of these supplemental methods was to step outside of the conventional systematic review and explore this heterogeneity from a broader perspective, based on the experience of palliative care researchers and practitioners. The gap analysis and expert consultations provided valuable input into possible underlying explanations in the evidence, which could be helpful in the further adaptation and testing of existing rHBPC interventions or the development and evaluation of new ones. We feel that such a combination of methods could prove accessible, understandable, and useful in informing decisions and could thus help increase the relevance of systematic reviews to the decision-making process.

Ten-year follow-up study of three alternative bearing surfaces used in total hip arthroplasty in young patients: a prospective randomised controlled trial.

AIMS: We present the ten-year data of a cohort of patients, aged between 18 and 65 years (mean age 52.7 years; 19 to 64), who underwent total hip arthroplasty. Patients were randomised to be treated with a cobalt-chrome (CoCr) femoral head with an ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE) or ceramic-on-ceramic (CoC) bearing surface. PATIENTS AND METHODS: A total of 102 hips (91 patients) were randomised into the three groups. At ten years, 97 hips were available for radiological and functional follow-up. Two hips (two patients) had been revised (one with deep infection and one for periprosthetic fracture) and three were lost to follow-up. Radiological analysis was performed using a validated digital assessment programme to give linear, directional and volumetric wear of the two polyethylene groups. RESULTS: There was a significantly reduced rate of steady-state linear wear with XLPE (0.07 mm/yr) compared with UHMWPE (0.37 mm/yr) (p = 0.001). Volumetric wear was also significantly reduced in the XLPE group (29.29 mm3/yr) compared with the UHMWPE group (100.75mm3/yr) (p = 0.0001). There were six patients with UHMWPE who had non-progressive osteolysis and none in the XLPE group. All three bearing groups had significant improvements in 12-item short form health survey scores, Western Ontario and McMaster Universities Osteoarthritis Index score and Harris Hip Score. However, the improvement in HSS was significantly less in the UHMWPE group (p = 0.0188) than in the other two groups. At ten years, the rates of volumetric and linear wear in the XLPE group remain low and predominantly below the estimated threshold for osteolysis (1 mm/yr). The rate of linear wear in the XLPE group was three times less than in the UHMWPE group at five-year follow-up and five times less at ten years. The rate of volumetric wear was also three times less in the XLPE group at ten years. CONCLUSION: While CoC also performs well, XLPE at ten years remains a safe and excellent bearing option in young patients, with low rates of wear and no evidence of osteolysis. Cite this article: Bone Joint J 2017;99-B:1590-5.

N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor.

Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. Objective To define the molecular mechanisms through which VWF N-linked glycan structures influence in vivo clearance. Methods By use of a series of exoglycosidases, different plasma-derived VWF (pd-VWF) glycoforms were generated. In vivo clearance of these glycoforms was then assessed in VWF-/- mice in the presence or absence of inhibitors of asialoglycoprotein receptor (ASGPR), or following clodronate-induced macrophage depletion. Results Reduced amounts of N-linked and O-linked sialylation resulted in enhanced pd-VWF clearance modulated via ASGPR. In addition to this role of terminal sialylation, we further observed that progressive N-linked glycan trimming also resulted in markedly enhanced VWF clearance. Furthermore, these additional N-linked glycan effects on clearance were ASGPR-independent, and instead involved enhanced macrophage clearance that was mediated, at least in part, through LDL receptor-related protein 1. Conclusion The carbohydrate determinants expressed on VWF regulate susceptibility to proteolysis by ADAMTS-13. In addition, our findings now further demonstrate that non-sialic acid carbohydrate determinants expressed on VWF also play an unexpectedly important role in modulating in vivo clearance through both hepatic ASGPR-dependent and macrophage-dependent pathways. In addition, these data further support the hypothesis that variation in VWF glycosylation may be important in the pathophysiology underlying type 1C VWD.

Self-report pain and symptom measures for primary dysmenorrhoea: a critical review.

Primary dysmenorrhoea (PD) is highly prevalent among women of reproductive age and it can have significant short- and long-term consequences for both women and society as a whole. Validated symptom measures are fundamental for researchers to understand women's symptom experience of PD and to test symptom interventions. The objective of this paper was to critically review the content and psychometric properties of self-report tools to measure symptoms of PD. Databases including PubMed, PsychoINFO, Cumulative Index of Nursing and Allied Health Literature, and Health and Psychosocial Instruments were searched for self-report symptom measures that had been used among women with either PD or perimenstrual symptoms. A total of 15 measures met inclusion criteria and were included in the final analysis. The measures were categorized into generic pain measures, dysmenorrhoea-specific measures, and tools designed to measure perimenstrual symptoms. These measures had varying degrees of comprehensiveness of symptoms being measured, relevance to PD, multidimensionality and psychometric soundness. No single measure was found to be optimal for use, but some dysmenorrhoea-specific measures could be recommended if revised and further tested. Key issues in symptom measurement for PD are discussed. Future research needs to strengthen dysmenorrhoea-specific symptom measures by including a comprehensive list of symptoms based on the pathogenesis of PD, exploring relevant symptom dimensions beyond symptom severity (e.g., frequency, duration, symptom distress), and testing psychometric properties of the adapted tools using sound methodology and diverse samples.

Specialist integrated haematological malignancy diagnostic services: an Activity Based Cost (ABC) analysis of a networked laboratory service model.

AIMS: Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) were introduced as a standard of care within the UK National Health Service to reduce diagnostic error and improve clinical outcomes. Two broad models of service delivery have become established: 'co-located' services operating from a single-site and 'networked' services, with geographically separated laboratories linked by common management and information systems. Detailed systematic cost analysis has never been published on any established SIHMDS model. METHODS: We used Activity Based Costing (ABC) to construct a cost model for our regional 'networked' SIHMDS covering a two-million population based on activity in 2011. RESULTS: Overall estimated annual running costs were £1 056 260 per annum (£733 400 excluding consultant costs), with individual running costs for diagnosis, staging, disease monitoring and end of treatment assessment components of £723 138, £55 302, £184 152 and £94 134 per annum, respectively. The cost distribution by department was 28.5% for haematology, 29.5% for histopathology and 42% for genetics laboratories. Costs of the diagnostic pathways varied considerably; pathways for myelodysplastic syndromes and lymphoma were the most expensive and the pathways for essential thrombocythaemia and polycythaemia vera being the least. CONCLUSIONS: ABC analysis enables estimation of running costs of a SIHMDS model comprised of 'networked' laboratories. Similar cost analyses for other SIHMDS models covering varying populations are warranted to optimise quality and cost-effectiveness in delivery of modern haemato-oncology diagnostic services in the UK as well as internationally.

Psychological adjustment in adults with cancer: the self as mediator.

The role of the self in adjustment to cancer has been noted but is not well understood. Research and theory on the self suggest that discrepancies between actual and ideal self-conceptions influence adjustment and mediate the effects of disease-related health problems on psychological well-being. This relationship was investigated in a cross-sectional study of 108 persons with cancer. Cancer patients who had more symptoms and worse functional health and perceived their cancer as a chronic rather than an acute disease had higher levels of self-discrepancies and poorer adjustment. Self-discrepancy was a significant mediator of the effects of perceived health status on purpose in life, positive relations with others, and depression.

Patient satisfaction and pain severity as outcomes in pain management: a longitudinal view of one setting's experience.

Longitudinal data from quality assurance studies of pain outcomes (pain severity and patient satisfaction) were critically examined to explore the reasons that patients are satisfied with their care even when they are in pain. Data were acquired from three sources: self-report surveys of patients during inpatient admission or ambulatory clinic visit (N = 306), telephone interviews of patients after discharge (N = 869), and chart reviews (N = 112). These data were compared to baseline data obtained 2 years ago, before the implementation of a number of programs designed to improve pain management. Findings reveal little change from baseline with respect to patient satisfaction with pain management--an overwhelming percentage are satisfied or highly satisfied. Similarly, there has been little change in pain intensity ratings--on average, patients' worst pain is approximately 7 on a 0-10 scale. In addition, almost all analgesic orders continue to be written for "as needed" administration. Based on these findings, we postulate that patients are satisfied even though they are in pain because they experience a commonly expected peak and trough pattern of pain relief, a pattern that occurs with "as needed" administration. That is, we conclude that pattern of pain relief, not pain severity, may be the critical determinant of satisfaction.

Perceived control mediates the relationship between pain severity and patient satisfaction.

The factors that account for patient satisfaction with acute pain management remain a mystery. Consistently, there has been an inverse, but very small association between pain severity and patient satisfaction; most patients are in severe pain, yet report they are satisfied with pain management. The hypothesis that perceived control mediates the relationship between pain severity and patient satisfaction was examined in 137 patients who underwent elective inpatient orthopedic surgery. Postoperatively, patients rated their pain severity (the highest level of pain experienced), their perceptions of control over the pain and taking pain medication, and their satisfaction with the relief they obtained from analgesics. Path analysis using LISREL was used to test for mediation. Pain severity was associated inversely with perceptions of control over pain and with satisfaction. There was a significant association between perceived control and satisfaction and perceived control partially mediated the relationship between pain severity and satisfaction. Although individuals who report experiencing severe pain are less satisfied with pain relief than individuals with less pain, it is the interpretation or perception of having control over the pain that most relates to satisfaction with pain relief. Clinically, it is important to examine ways in which individuals control their pain, teach them methods to exert control, and educate them that it is preferable to not allow pain to become severe--it is easier to "control" pain if you intervene at an early point.

Judgments of concept similarity by normal and aphasic subjects: relation to naming and comprehension.

A study was conducted in which aphasic patients, age-matched normals, and normal young adults performed five types of matching judgments for object pictures. These required matching for physical identity, basic object identity, and membership in the same superordinate category. Spoken name-to-picture matching was tested for the last two conditions. An analogous set of conditions was presented for letters. Latency patterns across the conditions showed general slowing for the aphasic patients, but with a differential decrement in the conditions that involved auditory (spoken name) input for the matching task. Results showed that variations in semantic judgment capability among the aphasics did not predict the patients' object naming ability.

Decision latencies for phonological and semantic information in object identification.

Several on-line studies in the literature have been cited in support of a two-stage model of name-retrieval in which semantic processing precedes and mediates access to phonology. Because of inconsistencies in prior studies an off-line experiment was designed to provide converging evidence on this issue. An experiment is reported in which young and elderly adults were required to give speeded judgments of whether a pictured object matched a named category, a named physical attribute, or a rhyming cue. Latencies for the young adults were fastest for category judgments and slowest for rhyming judgments. For the elderly adults physical attributes and rhyming judgments were equivalent. Results are discussed in terms of "lemma" theory in object naming.

Patient-related barriers to cancer pain management in Taiwan.

The reluctance of patients with cancer to report pain and to use analgesics hinders the management of their pain. In the United States, this reluctance is related to the patient's misconceptions regarding addiction and tolerance to analgesics and the desire to be a "good patient" who does not complain. Reports in the literature suggest that patients in Taiwan may have these same concerns and misconceptions. This study was designed to explore (a) the concerns of patients in Taiwan about reporting pain and using analgesics and (b) the relationship between these concerns and the adequacy of analgesics used by the patients. Sixty-three patients with cancer completed the Barriers Questionnaire-Taiwan (BTQ) form, a self-report instrument that measures the extent to which patients have eight specific concerns about reporting pain and using analgesics. The responses indicated that patients who were less educated were more likely to have concerns and that patients in general were most worried about tolerance. Patients who were inadequately medicated, as determined by an index of "adequate pain management" constructed for the study, had significantly higher levels of concerns. Open communication between health professionals and patients and educational programs about pain and about the concerns measured in this study could help overcome these concerns and misconceptions and improve pain management.

Caregiving demands and appraisal of stress among family caregivers.

Ambulatory treatment for cancer has increased patients' self-care requirements and placed demands on family members to manage the illness and treatment side effects at home. This exploratory study was undertaken to assess family caregiving demands (load) and to examine caregivers' appraisals of the illness/caregiving experience. Forty-seven persons involved in the care of patients receiving radiotherapy for cancer were observed. Appraisal of stress was measured with the Appraisal of Caregiving Scale (ACS). This newly developed measure, derived from cognitive appraisal theory, is designed to assess the intensity of four possible appraisals of caregiving: harm/loss, threat, challenge, or benign. Participants also completed the Caregiver Load Scale, a measure of the time spent in caregiving activities. Satisfactory reliabilities were obtained for both measures. Family caregivers reported spending the most time in providing transportation, giving emotional support, and in extra household tasks. They received the most assistance from family and friends, and made minimal use of professional services. Caregiver load was correlated positively with the length of time on treatment and with patient dependency. Caregivers in the poorest health, those with less education, and those of lower socioeconomic status had higher scores on the ACS appraisals of harm/loss and threat. Older caregivers had significantly higher challenge and benign appraisals. There was a strong positive correlation between caregiver load and the harm/loss and threat appraisals. Findings suggest a need for frequent reassessment of demands on family caregivers throughout the course of treatment and offer direction for future research.

Responding maintained under intermittent schedules of electric-shock presentation: "Safety" or schedule effects?

Four experiments were conducted in which lever pressing by squirrel monkeys was maintained under multiple, mixed, or chained schedules of electric-shock presentation. In the first two experiments, a multiple schedule was employed in which a fixed-interval schedule of shock presentation alternated with a signaled two-minute component. Initially, no events were scheduled during the two-minute component (a safety period). In the first experiment, the safety period was "degraded" by introducing and systematically increasing the frequency of periodic shocks presented during that component. In the second experiment, the proportion of overall safe time to unsafe time was decreased by decreasing the value of the fixed-interval schedule while holding constant shock frequency during the two-minute component. In the third experiment, the overall arrangement was changed from a multiple to a mixed schedule in an attempt to determine whether fixed-interval responding would be maintained when a single exteroceptive stimulus was associated with both components. In the fourth experiment, the overall arrangement was changed from a multiple to a chained schedule in an effort to determine whether fixed-interval responding would be maintained when its consequence was presentation of a signaled "unsafe" period. Fixed-interval responding was well maintained under all experimental conditions; the varied relationships obtained lend more support to conceptualizations of shock-maintained behavior as exemplifying schedule-controlled behavior than to suggestions that such behavior may be readily accounted for by "safety theory."

The role of the self in adjustment to cancer in elderly women.

One way that people may adjust to illness is through a redefinition of the self, especially with respect to the relationship between ideal self and actual self. To investigate psychological adjustment in community-dwelling elderly women, women with cancer (n = 17) were compared to women with other health problems (n = 30) based on measures of psychological distress and well-being, actual self, ideal self, and the discrepancy between actual self and ideal self. Women with cancer scored no differently than other women on measures of psychological well-being, psychological distress, and actual self, but their ideal-self ratings were lower. The positive adjustment of women with cancer may be the result of their ability to lower their ideal-self expectations, thereby reducing self-discrepancies that can result in psychological distress.

Nurse and patient satisfaction with three types of venous access devices.

PURPOSE/OBJECTIVES: To examine patient and nurse satisfaction with three types of venous access devices (VADs)--port, Groshong (Bard Access Systems, Salt Lake City, UT), and Hicman (Bard Access Systems)--and to identify the problems and benefits experienced with each type of device. DESIGN: A descriptive, correlational quality-assurance study. SETTING: An outpatient oncology/hematology clinic in a midwestern United States academic hospital with a comprehensive cancer center. SAMPLE: A convenience sample of 85 patients who had a port, Groshong catheter, or Hickman catheter and the clinic nurses who provided their care. METHOD: Consecutive patients meeting study criteria were invited to complete self-report questionnaires at the time of their clinic visits. Clinic nurses who cared for these patients also completed questionnaires. FINDINGS: Patients' reports of benefits did not differ by device, but they reported fewer blood-drawing problems with ports than with Groshong on Hickman catheters. Patients and nurses reported infections and clots more often with Groshong catheters than with the other two devices, Patients indicated that healthcare workers seemed most knowledgeable about Hickman catheters. Patients with ports reported more problems with access to the device, development of hematomas, and anxiety. Nurses reported more flow rate problems with Groshong catheters than with Hickman catheters. Patients and nurses reported no flow rate problems with ports. CONCLUSIONS: Each device was associated with a specific problem, yet in the global satisfaction ratings, patients expressed the greatest satisfaction with Hickman catheters and ports. Nurses tended to be least satisfied with Groshong catheters. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to ensure that other care providers have appropriate information on the care of VADs. This could be accomplished via written instructions on VAD care and followup telephone calls to care providers. A need exists for continued patient education on VAD care to minimize complications. The selection of an appropriate VAD should be based on the patient's best interests rather than on nurses' preferences.

Tetracycline sclerotherapy for the treatment of recurrent pooling of plasma in the submandibular tissue space: case report.

We present an unusual case of recurrent swelling after removal of the submandibular and sublingual salivary glands which was found to be the result of a collection of plasma. This was successfully treated by an injection of tetracycline to induce sclerosis.