Allied health transdisciplinary models of care in hospital settings: A scoping review  .

Improving the productivity of the allied health workforce is a global priority in response to the increasing incidence of chronic disease, associated healthcare costs, and insufficient workforce volume. Team-based healthcare, specifically allied health transdisciplinary teams, might be a solution to improve the utilization of workforce while maintaining high-quality and value-based healthcare. Allied health transdisciplinary teams can be a valuable solution in settings where care is delivered by different allied health professionals. Transdisciplinary teams embrace overlapping skills and blur traditional professional boundaries, allowing one professional to deliver certain aspects of care without eroding the skills and knowledge that each profession offers. The objective of this scoping review is to systematically examine and map the characteristics, outcomes, facilitators, and barriers of contemporary allied health transdisciplinary models of care that have been implemented in hospital settings. The scoping review was guided by the Joanna Briggs Institute methodology and reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Three screening rounds were completed by two independent reviewers. Included sources were synthesized using descriptive and tabular analysis. Nine studies that evaluated hospital-based allied health transdisciplinary teams were included. One study was a randomized controlled trial, five were experimental quantitative studies, two utilized qualitative analyses, and one was a conference abstract. Most studies reported improvements in time-efficiency, quality of care, and positive stakeholder perceptions. One study reported labor and capital cost savings. Barriers and facilitators of transdisciplinary teams were categorized by the authors as person/interpersonal, workflow, organizational or implementation factors. This review presents some evidence that demonstrates the potential of hospital-based allied health transdisciplinary teams, however high-quality evidence is scarce. Further primary research should focus on stakeholder perceptions, and labor and capital cost outcomes.

Protocol of trans-Tasman feasibility randomised controlled trial of the Younger Women's Wellness After Breast Cancer (YWWACP) lifestyle intervention.

BACKGROUND: Younger women (defined as those < 50 years who are likely pre-menopausal at time of diagnosis) with breast cancer often experience persistent treatment-related side effects that adversely affect their physical and psychological wellbeing. The Women's Wellness After Cancer Program (WWACP) was adapted and piloted in Australia to address these outcomes in younger women. The aims of this feasibility study are to determine (1) the potential to translate the Younger WWACP (YWWACP) intervention to a broader population base in Aotearoa/New Zealand and Australia, and (2) the potential for success of a larger, international, phase ΙΙΙ, randomised controlled trial. METHODS: This bi-national, randomised, single-blinded controlled trial involves two main study sites in Aotearoa/New Zealand (Kowhai study) and Australia (EMERALD study). Young women aged 18 to 50 years who completed intensive treatment (surgery, chemotherapy, and/or radiotherapy) for breast cancer in the previous 24 months are eligible. The potential to translate the YWWACP to women in these two populations will be assessed according to several feasibility outcomes. These include examining intervention accessibility, acceptability and uptake; intervention sustainability and adherence; the prevalence components of the intervention in the control group; intervention efficacy; participants' perception of measurement burden; the effectiveness of planned recruitment strategies; and trial methods and procedures. The studies collectively aim to enrol 60 participants in the intervention group and 60 participants in the control group (total = 120 participants). DISCUSSION: Ethical approval has been received from the Southern Health and Disability Ethics Committee (Kowhai ref: 19/STH/215), and UnitingCare Human Research Ethics Committee (EMERALD ref: 202103). This study will provide important data on the feasibility of the refined YWWACP in the trans-Tasman context. This study will account for and harmonise cross-country differences to ensure the success of a proposed international grant application for a phase ΙΙΙ randomised controlled trial of this program to improve outcomes in younger women living with breast cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): Kowhai ACTRN12620000260921 , registered on 27 February 2020. EMERALD ACTRN12621000447853 , registered on 19 April 2021.

Effects of exercise on vasomotor symptoms in menopausal women: a systematic review and meta-analysis.

The frequency and severity of menopausal vasomotor symptoms negatively impact quality of life. This systematic review evaluates the potential of exercise to relieve the subjective frequency and severity of vasomotor symptoms. We searched four databases to identify randomized controlled trials (RCTs) that evaluated the effect of structured exercise (e.g. aerobic training) on the severity and/or frequency of vasomotor symptoms in menopausal women. Two reviewers independently screened records for eligibility, extracted data and assessed risks of bias and evidence certainty using the Cochrane tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE). When suitable, data were pooled using random-effect meta-analyses. We appraised 21 RCTs involving 2884 participants. Compared to no-treatment control, exercise significantly improved severity of vasomotor symptoms (10 studies, standardized mean difference [SMD] = 0.25; 95% confidence interval [CI]: 0.04 to 0.47, p = 0.02, very low certainty of evidence); the effect size was attenuated when studies with a high risk of bias were excluded (SMD = 0.11, 95% CI: -0.03 to 0.26, p = 0.13). No significant changes in vasomotor frequency were found between exercise and control (SMD = 0.14, 95% CI: -0.03 to 0.31, p = 0.12, high certainty of evidence). In conclusion, exercise might improve vasomotor symptom severity. Future rigorous RCTs addressing the limitations of current review are warranted to explore the optimal exercise prescription principles to target the severity of vasomotor symptoms.

Cancer cachexia: an overview of diagnostic criteria and therapeutic approaches for the accredited practicing dietitian.

BACKGROUND: Cancer cachexia (CC) is a multifactorial syndrome characterised by ongoing skeletal muscle loss that leads to progressive functional impairment driven by reduced food intake and abnormal metabolism. Despite the traditional use of non-volitional weight loss as the primary marker of CC, there is no consensus on how to diagnose and manage CC. METHODS: The aim of this narrative review was to describe and discuss diagnostic criteria and therapeutic approaches for the accredited practicing dietitian with respect to identifying and managing CC. RESULTS: Available diagnostic criteria for cachexia include the cancer-specific (Fearon and Cachexia Score) and general criteria (Evans and Global Leadership Initiative on Malnutrition). These include phenotypic criteria [weight loss, body mass index, (objective) muscle mass assessments, quality of life] and aetiological criteria (disease burden, inflammation, energy expenditure, anorexia and inadequate food intake) and can be incorporated into the nutrition care process (NCP). This informs the nutrition diagnosis of 'chronic disease- or condition-related malnutrition (undernutrition) as related to increased nutrient needs, anorexia or diminished intake due to CC'. Optimal nutrition care and management of CC is multidisciplinary, corrects for increased energy expenditure (via immunonutrition/eicosapentaenoic acid), suboptimal protein/energy intake and poor nutrition quality of life, and includes a physical exercise intervention. Monitoring of intervention efficacy should focus on maintaining or slowing the loss of muscle mass, with weight change as an alternative gross indicator. CONCLUSIONS: Dietitians and the NCP can play an essential role with respect to identifying and managing CC, focusing on aspects of nutrition screening, assessment and intervention.

Benchmarking nurse outcomes in Australian Magnet® hospitals: cross-sectional survey.

BACKGROUND: Positive reports of nursing-related outcomes such as quality nursing care, nursing engagement with work and good practice environment are crucial in attaining and maintaining Magnet® designation. The majority of Magnet®-designated organisations (N = 482) are in the USA, with their aggregate nursing outcomes widely published as benchmark data. Australian Magnet® outcomes have not been aggregated or published to date. METHODS: The aims are to benchmark educational preparation, occupational burnout, job satisfaction, intention to leave and working environment of nurses in Australian Magnet®-designated facilities and to determine the reliability of the Practice Environment Scale-Australia.The design is a cross-sectional multisite survey set in all three Australian Magnet®-designated organisations.The demographics included age, gender, level of education, years in practice, level of seniority and position title. Two items measured job satisfaction and intent to stay in current employment. The Maslach Burnout Inventory explored the three domains of nursing engagement: depersonalisation, personal achievement and emotional exhaustion. The Australian version of the Practice Environment Scale interrogated participants' perceptions of their work environments. RESULTS: 2004 nurses participated (response rate 45.9%). Respondents' mean age was 39.2 years (range 20-72). They were predominantly female and had worked in their current facility for more than 5 years. Eighty five percent had a minimum of a Bachelor's degree. Eighty-six percent of respondents were satisfied or very satisfied with their current position. Eighty eight percent had no intention of leaving their current employer within the next 12 months. Participants rated their hospitals highly in all domains of the practice environment. Respondents reported less burnout in the personal accomplishment and depersonalisation domains than in the emotional exhaustion domain, in which they reported average levels of burnout. The internal consistency of the Practice Environment Scale-Australia was confirmed in this sample (Cronbach α's 0.87-0.9 for subscales and 0.89 for composite score). CONCLUSION: In this paper, we present nursing outcome data from all Australian Magnet® hospitals for the first time. This provides a benchmark that facilitates comparison with nursing outcomes published by Australian non-Magnet® hospitals and with international Magnet® organisations.

Validation of a frailty index in older cancer patients with solid tumours.

BACKGROUND: Frailty is an indicator of physiological reserve in older people. In non-cancer settings, frailty indices are reliable predictors of adverse health outcomes. The aims of this study were to 1) derive and validate a frailty index (FI) from comprehensive geriatric assessment (CGA) data obtained in the solid tumour chemotherapy setting, and 2) to explore whether the FI-CGA could predict chemotherapy decisions and survival in older cancer patients with solid tumours. METHODS: Prospective cohort study of a consecutive series sample of 175 cancer patients aged 65 and older with solid tumours. A frailty index was calculated using an accumulated deficits model, coding items from the comprehensive geriatric assessment tool administered prior to chemotherapy decision-making. The domains of physical and cognitive functioning, nutrition, mood, basic and instrumental activities of daily living, and comorbidities were incorporated as deficits into the model. RESULTS: The FI-CGA had a right-skewed distribution, with median (interquartile range) of 0.27 (0.21-0.39). The 99% limit to deficit accumulation was below the theoretical maximum of 1.0, at 0.75. The FI-CGA was significantly related (p < 0.001) to vulnerability as assessed by the Vulnerable Elders Survey-13 and to medical oncologists' assessments of fitness or vulnerability to treatment. Baseline frailty as determined by the FI-CGA was also associated with treatment decisions (Treatment Terminated, Treatment Completed, No Planned Treatment) (p < 0.001), with the No Planned Treatment group significantly frailer than the other two groups. CONCLUSION: The FI-CGA is a potentially useful adjunct to cancer clinical decision-making that could predict chemotherapy outcomes in older patients with solid tumours.

Heart failure following cancer treatment: characteristics, survival and mortality of a linked health data analysis.

BACKGROUND: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. A patient may survive cancer only to develop heart failure (HF), which has a higher mortality rate than some cancers. AIM: This study aimed to describe the characteristics and outcomes of HF in patients with blood or breast cancer after chemotherapy treatment. METHODS: Queensland Cancer Registry, Death Registry and Hospital Administration records were linked (1996-2009). Patients were categorised as those with an index HF admission (that occurred after cancer diagnosis) and those without an index HF admission (non-HF). RESULTS: A total of 15 987 patients was included, and 1062 (6.6%) had an index HF admission. Median age of HF patients was 67 years (interquartile range 58-75) versus 54 years (interquartile range 44-64) for non-HF patients. More men than women developed HF (48.6% vs 29.5%), and a greater proportion in the HF group had haematological cancer (83.1%) compared with breast cancer (16.9%). After covariate adjustment, HF patients had increased mortality risk compared with non-HF patients (hazard ratios 1.67 (95% confidence interval, 1.54-1.81)), and 47% of the index HF admission occurred within 1 year from cancer diagnosis and 70% within 3 years. CONCLUSION: Cancer treatment may place patients at a greater risk of developing HF. The onset of HF occurred soon after chemotherapy, and those who developed HF had a greater mortality risk.

Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) is a valid screening tool in chemotherapy outpatients.

PURPOSE: In the oncology population where malnutrition prevalence is high, more descriptive screening tools can provide further information to assist triaging and capture acute change. The Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) is a component of a nutritional assessment tool which could be used for descriptive nutrition screening. The purpose of this study was to conduct a secondary analysis of nutrition screening and assessment data to identify the most relevant information contributing to the PG-SGA SF to identify malnutrition risk with high sensitivity and specificity. METHODS: This was an observational, cross-sectional study of 300 consecutive adult patients receiving ambulatory anti-cancer treatment at an Australian tertiary hospital. Anthropometric and patient descriptive data were collected. The scored PG-SGA generated a score for nutritional risk (PG-SGA SF) and a global rating for nutrition status. Receiver operating characteristic curves (ROC) were generated to determine optimal cut-off scores for combinations of the PG-SGA SF boxes with the greatest sensitivity and specificity for predicting malnutrition according to scored PG-SGA global rating. RESULTS: The additive scores of boxes 1-3 had the highest sensitivity (90.2 %) while maintaining satisfactory specificity (67.5 %) and demonstrating high diagnostic value (AUC = 0.85, 95 % CI = 0.81-0.89). The inclusion of box 4 (PG-SGA SF) did not add further value as a screening tool (AUC = 0.85, 95 % CI = 0.80-0.89; sensitivity 80.4 %; specificity 72.3 %). CONCLUSIONS: The validity of the PG-SGA SF in chemotherapy outpatients was confirmed. The present study however demonstrated that the functional capacity question (box 4) does not improve the overall discriminatory value of the PG-SGA SF.

Cross-sectional survey of the health behaviour of southeast Queensland women with cancer-treatment induced menopause: implications for cancer and primary care nurses.

PURPOSE: Women who experience cancer treatment-induced menopause are at risk of long-term chronic morbidity. This risk can be prevented or offset with adherence to health promotion and risk reduction guidelines. The purpose of this study was to explore health behaviours in younger female survivors of cancer and the variables (quality of life and psychological distress) believed to moderate health behaviours. DESIGN: Cross-sectional survey of a convenience sample of women (n=85) in southeast Queensland. METHODS: Health behaviour and health status were elicited with items from the Australian Health Survey and the Behavioural Risk Factor Surveillance System. The WHO Quality of Life (Brief) measured participants' self-reported quality of life and their satisfaction with their health. The Brief Symptom Inventory-18 measured psychological distress. FINDINGS: Higher self-reported health status was associated with regular exercise and better quality of life. However, a substantial proportion of participants did not engage in the physical activity, dietary or cervical screening practices recommended by Australian guidelines. CONCLUSIONS: The participants require education regarding the benefits of diet, exercise, weight loss and decreased alcohol intake, as well as information on future health risks and possible comorbidities. These education sessions could be addressed by a nurse-led health promotion model of care at the time of discharge or in the community.

Dietary modification for women after breast cancer treatment: a narrative review.

Diet is thought to account for about 25% of cancers in developed countries. It is well documented that the risks associated with both the breast cancer itself and its treatments are important for women previously treated for breast cancer. Women are at risk of recurrence of the primary disease and prone to develop treatment-induced co-morbidities, some of which are thought to be modified by diet. With a view to making dietary recommendations for the breast cancer patients we encounter in our clinical nursing research, we mined the literature to scope the most current robust evidence concerning the role of the diet in protecting women against the recurrence of breast cancer and its potential to ameliorate some of the longer-term morbidities associated with the disease. We found that the evidence about the role of the diet in breast cancer recurrence is largely inconclusive. However, drawing on international guidelines enabled us to make three definitive recommendations: women at risk of breast cancer recurrence, or who experience co-morbidities as a result of treatment, should limit their exposure to alcohol, moderate their nutritional intake so it does not contribute to post-menopausal weight gain, and should adhere to a balanced diet. Nursing education planned for breast cancer patients about dietary issues should ideally be individually tailored, based on a good understanding of the international recommendations and the evidence underpinning them.

Association of gestational diabetes with abnormal maternal vascular endothelial function.

OBJECTIVE: To evaluate vascular endothelial function in isolated small arteries from women with gestational diabetes. METHODS: Small subcutaneous arteries (mean luminal diameter approximately 250 microns) were dissected from biopsies obtained at caesarean section in 14 normotensive women with gestational diabetes and in 18 normotensive nondiabetic pregnant women. Vascular function was determined after mounting the arteries on a small vessel myograph. RESULTS: Pre-constricted arteries from gestational diabetic pregnant women demonstrated poor relaxation to acetylcholine, an endothelium-dependent vasodilator (pEC50, mean [SE], 6.98 [0.10] vs normal pregnant, 7.28 [0.08], P < 0.03; % maximum relaxation, median [range], 88.2 [42.4-99.4] vs normal pregnant 94.2 [71.8-100.0], P < 0.01). In the presence of indomethacin relaxation to acetylcholine was similar in both groups suggesting a deficiency in dilator prostaglandin synthesis in the arteries from the diabetic women. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine further reduced sensitivity of arteries to acetylcholine but to a similar degree in both normal pregnant and gestational diabetic women. Relaxation to sodium nitroprusside, an indicator of sensitivity of the vascular smooth muscle to nitric oxide, was similar in both groups. CONCLUSIONS: Maternal vascular endothelial dysfunction may contribute to the increased incidence of cardiovascular disorders in women with gestational diabetes.

Control of vascular resistance in the maternal and feto-placental arterial beds.

This review aims to provide a comprehensive summary of the mechanisms involved in the physiological adaptation of the vasculature to pregnancy. Profound changes occur both systemically and in discrete circulations in the mother, but it is debatable which factors are responsible. Similarly, whilst the feto-placental circulation must be substantially controlled by humoral mechanisms, the exact role of each potential contributor is not known. In view of the hitherto unappreciated and very important role of the endothelium-derived vasodilator, nitric oxide, in the control of peripheral vascular resistance, considerable emphasis will be placed on the many recent investigations in this area.

Endothelium-dependent relaxation of human resistance arteries in pregnancy.

OBJECTIVE: Reduced peripheral vascular resistance is an integral component of vascular adaptation in pregnancy. The precise mediators of the reduced resistance are unknown, however, and are often assessed by indirect means. In this study we investigated endothelium-dependent relaxation directly by examining acetylcholine-mediated relaxation in small arteries dissected from the subcutaneous fat layer undergoing biopsy at the time of gynecologic surgery and cesarean section. STUDY DESIGN: By means of a small vessel myograph we measured tension in resistance arteries of normal pregnant (n = 22) and nonpregnant (n = 10) women and assessed the contributions of vasodilatory prostanoids and endothelium-derived relaxing factor on endothelium-dependent relaxation, as elicited by acetylcholine (1 nmol/L to 10 mumol/L) after precontraction with 3 mumol/L norepinephrine. RESULTS: Endothelium-dependent relaxation was similar in arteries of pregnant and nonpregnant women. Sodium nitroprusside-induced relaxation was similar in arteries of pregnant and nonpregnant women. CONCLUSION: This study fails to demonstrate any increase in acetylcholine-induced endothelium-dependent relaxation in small subcutaneous arteries in pregnancy.

Functional characteristics of small placental arteries.

OBJECTIVES: The aim of this study was to investigate characteristics of placental arteries capable of influencing vasomotor tone in the fetoplacental vascular bed. Contractile characteristics and endothelium-dependent and endothelium-independent relaxation were examined. STUDY DESIGN: By means of a small vessel myograph arteries of mean normalized internal diameter 353.22 +/- 13.14 microns were studied under isometric conditions. Contractile function was assessed with a variety of agonists, including angiotensin II, endothelin-1, the thromboxane mimetic U46619, prostaglandin E2, and prostaglandin F2 alpha. The effect of physiologic and supraphysiologic PO2 on vascular function was also examined. Relaxation was assessed in response to known endothelium-dependent vasodilators, including acetylcholine, bradykinin, histamine, and A23187 and to sodium nitroprusside (endothelium independent). The effect of indomethacin and the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester on contractile function was also evaluated. RESULTS: Sensitivity to sodium nitroprusside was reduced by a high PO2. U46619 was the most potent constrictor agonist studied. The response of precontracted arteries to known endothelium-dependent vasodilators was minimal, other than for histamine, which led to modest relaxation. The constrictor response to U46619 was increased in the presence of NG-nitro-L-arginine methyl ester. CONCLUSIONS: Oxygen tension may be an important determinant of relaxation in small placental arteries. Receptor-mediated release of endothelium-derived relaxing factor is not a major mechanism in the fetoplacental circulation.

Abnormal endothelial cell function of resistance arteries from women with preeclampsia.

OBJECTIVE: There is substantial indirect evidence that the vascular endothelium may be dysfunctional in preeclampsia and that reduced production of endothelial-derived vasodilators may account for the increased vascular resistance and enhanced pressor sensitivity characteristic of this disorder. In this study we directly investigated endothelial function by examining acetylcholine-mediated relaxation in small arteries dissected from the subcutaneous fat layer examined at the time of cesarean section. STUDY DESIGN: By means of a small vessel myograph we measured tension in resistance arteries of normal pregnant women (n = 12) and women with preeclampsia (n = 12) and assessed the contributions of vasodilatory prostanoids and endothelium-derived relaxing factor to endothelium-dependent relaxation, as elicited by acetylcholine, 1 nmol/L to 10 mumol/L, after precontraction with 3 mumol/L norepinephrine. RESULTS: Endothelium-dependent relaxation was impaired in arteries of women with preeclampsia compared with arteries from normotensive pregnant women. Endothelium-independent relaxation as assessed by sodium nitroprusside was not altered in the arteries from preeclamptic women. CONCLUSIONS: This study provides direct evidence of abnormal endothelial function in preeclampsia. No deficiency in endothelium-independent relaxation could be detected.

Endothelium-dependent relaxation and noradrenaline sensitivity in mesenteric resistance arteries of streptozotocin-induced diabetic rats.

1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries of control and streptozotocin-induced diabetic rats. 2. The diabetic rats demonstrated enhanced vascular sensitivity to noradrenaline compared with age-matched controls (pEC50 5.99 +/- 0.06 for diabetic rats, n = 25, versus 5.82 +/- 0.03 for controls, n = 45, P < 0.05). 3. Significant impairment of acetylcholine-induced relaxation was observed in arteries from the diabetic animals compared with controls (pEC50 6.81 +/- 0.17 for diabetic rats, n = 21, versus 7.54 +/- 0.17 for controls, n = 45, P < 0.001). 4. The difference between acetylcholine-induced relaxation in diabetic and control arteries remained in the presence of 10 microM indomethacin (pEC50 6.41 +/- 0.11 for diabetic rats, n = 16, versus 7.59 +/- 0.08 for controls, n = 20, P < 0.001). 5. The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) produced profound inhibition of acetylcholine-induced relaxation in diabetic arteries but partial inhibition in controls. The incomplete inhibition of acetylcholine-induced relaxation by L-NMMA in the control arteries was the result of ineffective inhibition of nitric oxide synthase since an alternative inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), led to similar inhibition to that seen in the diabetic arteries with L-NMMA. The endothelium-derived relaxing factor (EDRF)-mediated component of acetylcholine-induced relaxation determined by use of the nitric oxide synthase inhibitors was, therefore, apparently reduced in diabetic rats compared with control animals.6. In further experiments L-NAME was found to enhance the response to noradrenaline in control rats but not in diabetic animals, suggesting that the abnormal response to noradrenaline in the diabetic animals was also due to reduced EDRF release.7. Nitroprusside-induced relaxation (endothelium-independent) was similar in arteries from control anddiabetic rats (pEC5o 7.61 +/- 0.13 for diabetic arteries, n = 18, versus 7.68 +/- 0.15 in the controls, n = 20, P not significant).8. These results suggest that endothelial function is abnormal in mesenteric resistance arteries of streptozotocin-induced diabetic rats and that this is predominantly due to reduced EDRF release.

Human herpes virus 6 and endogenous biotin in salivary glands.

AIMS: To detect the presence of human herpes virus 6 (HHV6) and endogenous biotin in paraffin wax embedded and frozen salivary glands. METHODS: Two stage indirect and streptavidin-biotin immunoperoxidase techniques were used to visualise the antigens. RESULTS: HHV6 could not be shown in any of the tissues. However, considerable endogenous biotin antigenicity was detected in the glandular elements of the paraffin wax embedded material. CONCLUSIONS: Results obtained with avidin-biotin detection systems should be interpreted with caution, especially when glandular epithelium is being stained. This may apply to both immunoperoxidase and in situ hybridisation techniques. The use of an anti-biotin antibody as a standard control should be considered.

Increase in severity of graft versus host disease by cytomegalovirus.

An allogeneic transplant recipient developed severe graft versus host disease (GvHD) 48 days after transplantation that was concomitant with a cytomegalovirus (CMV) viraemia, from which she subsequently died. CMV infection was detected in blood by the polymerase chain reaction and later in tissue by immunohistochemical techniques. CMV should be considered in patients in whom GvHD does not respond to appropriate treatment, and this case suggests that herpes viruses may increase the severity of GvHD by synergistically enhancing the graft versus host reaction.

Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer. An immunohistochemical study.

Expression of the estrogen-regulated lysosomal protease, cathepsin D, was studied in a series of 94 breast cancers using an immunohistochemical technique. Granular staining of tumor cell cytoplasm was detected in 62 cases. Positive staining was associated with a significant increase in overall time to relapse and when survival was analyzed in terms of intensity of cathepsin D staining there was a significant trend for both increased time to relapse and increased length of survival. The presence of estrogen receptor was associated with positive cathepsin D immunostaining, and in the subgroup of estrogen receptor-positive tumors cathepsin D staining was associated with significantly prolonged survival; this was not the case for estrogen receptor-negative tumors. Positive cathepsin D immunostaining was associated with significant prognostic advantage in patients with confirmed lymph node metastasis but not in node-negative patients. It is suggested that cathepsin D expression reflects the functional integrity of the estrogen response pathway. Cathepsin D may prove a clinically useful adjunct to assessment of estrogen receptor status.