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Introduction Targeted oral anticancer agents (OAAs) are increasingly used to treat cancer, including haematological malignancies and ovarian cancer, but they can cause serious symptomatic side effects such as arrhythmias, hypertension, and hyperglycaemia. Unaddressed OAA symptoms or inadequately managed symptoms may also lead to unnecessary and unscheduled healthcare use that decreases patient quality of life and financially burdens both patients and the healthcare system. Limited information is available about patient symptoms, self-management behaviours, and use of healthcare services over time while taking targeted OAAs, but is needed to ensure successful OAA therapy. The primary objective is to understand patient experiences and behaviours on initiating targeted OAA, and elicit cancer care clinicians’ (ie, physicians, advanced practice practitioners, nurses, and pharmacists) perspectives on supporting patients during therapy. Study results will inform comprehensive and realistic interventions that minimise disruptions to therapy while maximising quality of life.Methods and analysis We will conduct a remote single-arm, convergent-parallel mixed-methods cohort study within a large academic medical centre. A minimum of 60 patients will be enrolled. Patients will complete several validated patient-reported outcome measures at six timepoints over 6 months. Mixed-effects logistic regression will be used to predict the primary binary outcome of unscheduled healthcare use by patient self-efficacy for symptom self-management. Semistructured interviews will be conducted with patients and clinicians and thematically analysed. Triangulated quantitative and qualitative results will be reported using cross-case comparison joint display.Ethics and dissemination This study protocol is approved by the Institutional Review Board of University of Michigan Medical School (IRBMED). Study results will be published in peer-reviewed journals, presented at conferences, and disseminated to study participants.

Background COVID-19 has strained healthcare systems globally. In this and future pandemics, providers with limited critical care experience must distinguish between moderately ill patients and those who will require aggressive care, particularly endotracheal intubation. We sought to develop a machine learning-informed Early COVID-19 Respiratory Risk Stratification (ECoRRS) score to assist in triage, by providing a prediction of intubation within the next 48 hours based on objective clinical parameters.Methods Electronic health record data from 3447 COVID-19 hospitalizations, 20.7% including intubation, were extracted. 80% of these records were used as the derivation cohort. The validation cohort consisted of 20% of the total 3447 records. Multiple randomizations of the training and testing split were used to calculate confidence intervals. Data were binned into 4-hour blocks and labeled as cases of intubation or no intubation within the specified time frame. A LASSO (least absolute shrinkage and selection operator) regression model was tuned for sensitivity and sparsity.Results Six highly predictive parameters were identified, the most significant being fraction of inspired oxygen. The model achieved an area under the receiver operating characteristic curve of 0.789 (95% CI 0.785 to 0.812). At 90% sensitivity, the negative predictive value was 0.997.Discussion The ECoRRS score enables non-specialists to identify patients with COVID-19 at risk of intubation within 48 hours with minimal undertriage and enables health systems to forecast new COVID-19 ventilator needs up to 48 hours in advance.Level of evidence IV.

Objectives Explore the views of two main stakeholders: mental health professionals and volunteers from three European countries, on the provision of volunteering in mental healthcare.Design A multicountry, multilingual and multicultural qualitative focus group study (n=24) with n=119 participants.Participants Volunteers and mental health professionals in three European countries (Belgium, Portugal and the UK).Results Mental health professionals and volunteers consider it beneficial offering volunteering to their patients. In this study, six overarching themes arose: (1) there is a framework in which volunteering is organised, (2) the role of the volunteer is multifaceted, (3) every volunteering relationship has a different character, (4) to volunteer is to face challenges, (5) technology has potential in volunteering and (6) volunteering impacts us all. The variability of their views suggests a need for flexibility and innovation in the design and models of the programmes offered.Conclusions Volunteering is not one single entity and is strongly connected to the cultural context and the mental healthcare services organisation. Despite the contextual differences between these three European countries, this study found extensive commonalities in attitudes towards volunteering in mental health.

Recent infectious disease outbreaks, including the ongoing global COVID-19 pandemic and Ebola in the Democratic Republic of the Congo, have demonstrated the critical importance of resilient health systems in safeguarding global health security. Importantly, the human, economic and political tolls of these crises are being amplified by health systems’ inabilities to respond quickly and effectively. Improving resilience within health systems can build on pre-existing strengths to enhance the readiness of health system actors to respond to crises, while also maintaining core functions. Using data gathered from a scoping literature review, interviews with key informants and from stakeholders who attended a workshop held in Dhaka, Bangladesh, we developed a Health System Resilience Checklist (‘the checklist’). The aim of the checklist is to measure the specific capacities, capabilities and processes that health systems need in order to ensure resilience in the face of both infectious disease outbreaks and natural hazards. The checklist is intended to be adapted and used in a broad set of countries as a component of ongoing processes to ensure that health actors, institutions and populations can mount an effective response to infectious disease outbreaks and natural hazards while also maintaining core healthcare services. The checklist is an important first step in improving health system resilience to these threats, but additional research and resources will be necessary to further refine and prioritise the checklist items and to pilot the checklist with the frontline health facilities that would be using it. This will help ensure its feasibility and durability for the long-term within the health systems strengthening and health security fields.

Background Cognitive–behavioural theories of panic disorder posit that panic attacks arise from a positive feedback loop between arousal-related bodily sensations and perceived threat. In a recently developed computational model formalising these theories of panic attacks, it was observed that the response to a simulated perturbation to arousal provided a strong indicator of vulnerability to panic attacks and panic disorder. In this review, we evaluate whether this observation is borne out in the empirical literature that has examined responses to biological challenge (eg, CO2 inhalation) and their relation to subsequent panic attacks and panic disorder.Method We searched PubMed, Web of Science and PsycINFO using keywords denoting provocation agents (eg, sodium lactate) and procedures (eg, infusion) combined with keywords relevant to panic disorder (eg, panic). Articles were eligible if they used response to a biological challenge paradigm to prospectively predict panic attacks or panic disorder.Results We identified four eligible studies. Pooled effect sizes suggest that there is biological challenge response has a moderate prospective association with subsequent panic attacks, but no prospective relationship with panic disorder.Conclusions These findings provide support for the prediction derived from cognitive–behavioural theories and some preliminary evidence that response to a biological challenge may have clinical utility as a marker of vulnerability to panic attacks pending further research and development.Trial registration number 135908.

AIM--To assess the value of vimentin and cytokeratin (CK) intermediate filament proteins (IFPs) in distinguishing between nodular hyperplasia and carcinoma of the prostate and in predicting prognosis in prostatic cancer. METHODS--Fifteen carcinomas and 49 cases of nodular hyperplasia were studied using frozen sections and monoclonal antibodies to CK and vimentin IFPs. RESULTS--There was no statistically significant difference in vimentin expression between nodular hyperplasia and carcinoma. The luminal epithelium in both also reacted with antibodies which detect CK8, 18 and 19. CK 7 expression was found in 57% of cases of nodular hyperplasia and was not identified in any carcinoma. There was a reaction with antibodies to CK1, 2, 3, 4, 10, 11, and 13 in only a minority of cases. There was no statistically significant difference in vimentin and CK reactivity in high and low grade carcinomas. CONCLUSION--Neither vimentin nor CK expression assists in establishing whether a prostatic lesion is benign or malignant or in predicting the biological behaviour of a prostatic carcinoma. [ABSTRACT FROM PUBLISHER]

A case of signet-ring cell lymphoma affecting the bone marrow and diagnosed by bone marrow trephine biopsy is reported. Normal marrow was replaced totally by cells with large central vacuoles, many of which displaced the nucleus to the periphery of the cell, imparting a signet-ring appearance. Initially, the favoured morphological diagnosis was metastatic signet-ring adenocarcinoma, but on immunocytochemistry the tumour cells were strongly positive for CD45 (leucocyte common antigen) and the B cell marker CD20 (L26). Electron microscopy revealed electron-lucent vacuoles with no discernable internal structure. The tumour was classified as a high grade centroblastic lymphoma using the upgraded Kiel classification. Despite chemotherapeutic treatment, the patient died during an episode of septicaemic shock within two months of presentation. [ABSTRACT FROM PUBLISHER]

AIM--To carry out a comprehensive study of cytokeratin expression in benign and malignant breast epithelium and breast myoepithelial cells; to examine changes in the cytokeratin profile in malignant and benign epithelium and in carcinomas of increasing histological grade. METHODS--Frozen sections from fibroadenomas (19 cases), fibrocystic disease (19 cases), and infiltrating ductal (68 cases), lobular (seven cases), and mucinous carcinomas (three cases) were examined using a panel of monoclonal antibodies. RESULTS--The luminal epithelium in all fibroadenomas and all cases of fibrocystic disease, as well as tumour cells in most carcinomas, reacted with the specific antibodies to cytokeratins 7, 8, 18, and 19 and to antibodies which included these cytokeratins in their specificities (Cam 5.2, AE1, AE3, RCK102, and LP34). In a few ductal carcinomas none of the tumour cells reacted for cytokeratins 7, 8, or 18. Three ductal carcinomas expressed cytokeratin 14. Only occasional cases expressed cytokeratins 3, 4, 10, and 13. Antibodies which included cytokeratins 5 and 14 in their specificities detected myoepithelial cells less efficiently than antiactin antibodies. CONCLUSION--The cytokeratin profiles in the luminal epithelium in benign breast disease and in tumour cells in most carcinomas are similar in most cases. Some carcinomas, however, are negative for cytokeratins 7, 8, or 18. This may provide a means of predicting the biological behaviour of a histologically borderline lesion. [ABSTRACT FROM PUBLISHER]

AIMS--To determine vimentin expression in epithelial cells in benign breast disease and malignant breast tumours; to assess the value of vimentin expression as a prognostic indicator in breast carcinoma. METHODS--Frozen and formalin fixed, paraffin wax embedded sections from 78 carcinomas, three phyllodes tumours, 19 fibroadenomas and 19 cases of fibrocystic disease were examined with a monoclonal antibody from the V9 clone. A correlation between vimentin expression and known prognostic indicators was sought in ductal carcinomas. The intracellular localisation of vimentin was examined in benign and malignant lesions. RESULTS--Vimentin expression was identified on frozen section in the cells of ductal (53%), lobular (86%), and mucinous (33%) carcinomas and in the luminal epithelium of fibroadenomas (68%), cases of fibrocystic disease (47%), and a malignant phyllodes tumour. Formalin fixation reduced the percentage of carcinomas and cases of benign disease in which vimentin was detected. This reduction was more pronounced in fibroadenoma and fibrocystic disease than in ductal carcinoma. Associations were identified between vimentin expression as detected on frozen section and tumour grade, size, number of lymph nodes affected, oestrogen receptor content and growth fraction. Only the association with grade was significant (p = 0.045). There was no significant correlation between any of these prognostic variables and vimentin expression on paraffin wax sections. There was no difference in the intracellular localisation of vimentin staining between benign and malignant lesions, or between low and high grade ductal carcinomas. CONCLUSION--There is some loss of vimentin immunoreactivity after formalin fixation. Vimentin expression does not assist in differentiating between benign and malignant breast disease, but is correlated with tumour grade in ductal carcinoma. [ABSTRACT FROM PUBLISHER]

Conventional light and electron microscopic studies, together with cytochemical and immunocytochemical staining procedures, were carried out to ascertain whether the lymphomata of four elderly female patients living within 10 kilometers of each other, who presented within a short space of time with massive splenomegaly and varying cytopenia, belonged to any particular subgroup of lymphoma. In each case the lymphoma had a diffuse pattern and mature B cell phenotype. The malignant cells were of uniform cell type, slightly larger than admixed polymorphonuclear leucocytes, and showed minimal nuclear irregularity and positivity for tartrate resistant acid phosphatase (TRAP) staining. Their clinical and morphological features were compared with those of other lymphoproliferative disorders, but while sharing some features in common with each condition, this small group of patients seemed to have a unique combination of findings. The cytopenias of all four responded well after removal of the spleen and their disease has not been aggressive. It is concluded that these patients have a distinct subgroup of lymphoma, which it is important to recognise so that inappropriate use of aggressive cytotoxic drugs can be avoided. [ABSTRACT FROM PUBLISHER]

The need for specialised forms of clinical audit was highlighted by the report of the Confidential Enquiry into Perioperative Deaths (CEPOD). Necropsy rates in a Northern Ireland teaching hospital were studied with particular reference to perioperative deaths. To provide an overall context for these observations, the pattern of the necropsy services in Northern Ireland as a whole was also determined. For 600 consecutive deaths in a major teaching hospital, the overall necropsy rate was 180 (30%). In the 74 perioperative deaths in this group (as defined by the CEPOD) the necropsy rate was 26 (35%), compared with 16 out of 72 (22%) for other surgical deaths and 89 out of 386 (23%) for medical cases. More coroners' necropsies were carried out in the perioperative group. These figures are within the range of the CEPOD experience. In 1987, in the whole of Northern Ireland, there were 8859 hospital deaths, 520 (5.9%) hospital necropsies, and 516 (5.8%) coroners' necropsies, giving an overall necropsy rate of 11.7%. Outside the two major Belfast teaching hospitals, however, there were 6799 hospital deaths, 76.6% of all hospital deaths for Northern Ireland. In this group there were 180 (2.6%) hospital necropsies and 383 (5.6%) coroners' cases, the overall necropsy rate being only 8.2%. These wide variations reflect the fact that the number of pathologists in post in the peripheral areas of the province falls substantially short of levels recommended by the Royal College of Pathologists. If clinical audit along CEPOD lines is to be effective nationally, more emphasis should be placed on the value of necropsy and local deficiencies in provision will have to be identified and remedied. It is suggested that this could be achieved by combining audit provisions with budgetary incentives. [ABSTRACT FROM PUBLISHER]

The effects of cytotoxic therapy on the structure and function of the proximal jejunum were studied in six patients receiving intravenous cyclophosphamide (300 mg/m2), methotrexate (40 mg/m2), and 5-fluorouracil (600 mg/m2) as adjuvant therapy for breast cancer. Using a steady state, triple lumen tube perfusion system the absorption of water and electrolytes was measured before and 48 h after administration of the cytotoxic agents. Jejunal biopsies were obtained at each perfusion. Median (range) water absorption fell from 126 (40-142) to 84 (46-142) ml/h/30 cm, with parallel changes for electrolytes; none of the changes was significant. Brush border disaccharidases did not change at 48 h after chemotherapy, while mature enterocytes appeared normal by both light and electron microscopy. Crypt cells and immature enterocytes, however, showed focal vacuolation by light microscopy, corresponding to the occurrence of large residual bodies (secondary lysosomes) containing partially degraded fragments of damaged crypt cells. The confinement of ultrastructural changes to the immature cell population may explain the failure of this study to show a consistent change in the absorptive function of the jejunum 48 h after chemotherapy. [ABSTRACT FROM PUBLISHER]

A series of 213 perioperative deaths was studied out of a total of 1451 consecutive necropsies carried out over three years. Discrepancies between the clinical and the necropsy diagnosis were assessed under four classes of discrepant diagnosis: class I, patient survival affected, treatable; class II, patient survival affected but not treatable; class III, correlated to cause of death but treatable; and class IV, incidental diagnosis which could not have been made before death. Major discrepancies of classes I and II were found in 44 (21%) and 62 (29%) cases, respectively. Minor discrepancies of classes III and IV were found in 63 (30%) and 101 (47%) cases, respectively. No discrepancies were found in 50 (23.5%) cases. These results confirm the continuing value of the necropsy in the assessment of perioperative deaths. [ABSTRACT FROM PUBLISHER]

The case is argued for wider use of electron microscopy as an aid to histological diagnosis in problem cases such as tumours of uncertain histogenesis. In practical terms, electron microscopy can produce results as "immediate" as many special stains in regular use. The cost of providing an effective service can be favourably compared with that of various other diagnostic aids commonly called upon in normal clinical practice. It is suggested that exploitation of this growth area of morphological pathology will enhance the attractions of the discipline of histopathology to talented potential recruits. [ABSTRACT FROM PUBLISHER]

A case is described of primary hyperparathyroidism in a patient with both a parathyroid cyst within the thymus gland and a concomitant parathyroid adenoma. The parathyroid adenoma contained microcystic areas of degeneration, and it is thought that the parathyroid cyst reflected degenerative change in a pre-existing adenoma. Parathyroid cyst should be considered in the differential diagnosis of cystic lesions within the thymus. Fine needle aspiration and parathyroid hormone assay on cyst fluid may provide a preoperative diagnosis. [ABSTRACT FROM AUTHOR]