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Background: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 μg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. Methods: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. Results: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2–2.6). Median time from baseline CT to study drug was 62.5 (55–80) minutes, and from study drug to early post-dose CT was 19 (14.5–30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (−0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8–8.3) in the placebo arm ( P =0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (−2.6 to 8.3) in the rFVIIa arm and 0.7 mL (−1.6 to 2.1) in the placebo arm ( P =0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71–1.43]; P =0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994–1.003]; P =0.50; Table 3). Conclusions: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01359202.

Patellofemoral pain (PFP) is common and has a poor long-term prognosis. There is a lack of clarity about the clinical reasoning of recognised inter-disciplinary experts in the published literature.To help identify best practice by exploring the clinical reasoning of a range of inter-disciplinary experts that regularly diagnose and treat PFP.Qualitative study with semi-structured interviews.Recruitment resulted in a convenience sample for semi-structured interview, which were recorded and transcribed verbatim. Data were analysed until theoretical saturation, as determined by multiple investigators.Interviews with 19 clinical experts (15 men, 4 women; mean experience 18.6 years ± 8.6) from four broad professions yielded four themes. Firstly, the assessment and diagnosis process should include a thorough history and examination to rule in PFP. Secondly, information provision should aim to increase patients' understanding, aid in controlling symptoms, and facilitate behaviour change. Thirdly, active rehabilitation, which was a salient theme and included advocacy of combined hip and knee exercise that is adapted to the individual. Finally, treatment adjuncts, which can be used selectively to modify symptoms, may include running retraining, taping, or foot orthoses.PFP should be diagnosed clinically, and tailored treatment programmes should be prescribed for people with PFP. Exercise was considered the most effective treatment and underlying psychological factors should be addressed to improve prognosis.

Treatment with endovascular therapy in the extended time window for acute ischaemic stroke with large vessel occlusion involves stringent selection criteria based on the two landmark studies DAWN and DEFUSE3. Current protocols typically include the requirement of advanced perfusion imaging which may exclude a substantial proportion of patients from receiving a potentially effective therapy. Efforts to offer endovascular reperfusion therapies to all appropriate candidates may be facilitated by the use of simplified imaging selection paradigms with widely available basic imaging techniques, such as non-contrast CT and CT angiography. Currently available evidence from our literature review suggests that patients meeting simplified imaging selection criteria may benefit as much as those patients selected using advanced imaging techniques (CT perfusion or MRI) from endovascular therapy in the extended time window. A comprehensive understanding of the role of imaging in patient selection is critical to optimising access to endovascular therapy in the extended time window and improving outcomes in acute stroke. This article provides an overview on current developments and future directions in this emerging area.

Background Patellofemoral pain (PFP) is common and long-term treatment outcomes are unsatisfactory. Qualitative exploration of diagnosis and management from the perspective of people with PFP is lacking. Objectives To inform care and improve intervention delivery by exploring the experience of people with patellofemoral pain (PFP) regarding diagnosis and management. Design Qualitative study with semi-structured interviews. Method Online recruiting yielded a convenience sample of participants with PFP for semi-structured interviews. Interviews were recorded, transcribed verbatim and analysed using thematic analysis until theoretical saturation by multiple investigators to determine themes and sub-themes. Results 12 participants were interviewed, with three themes identified; the value of diagnosis, the need for tailored (individualised) care, and the role of education. Participants viewed a diagnosis as essential to guide management, yet this was rarely provided, causing uncertainty about pain mechanisms; “it's nice to be told what it is that's wrong”. Interventions needed to be tailored to the individual as not all participants responded in the same way to treatment(s) or had the same needs; “everyone copes and reacts differently”. Finally, participants viewed education as essential to empower them to understand and manage the condition; “if I'd have been given more information, I think I'd know how to deal with it more”. Conclusions The overarching narrative from three themes was a desire for clearly communicated personalised care that meets individual needs. People with PFP desire a diagnosis to explain their pain, tailored interventions, and appropriate education to optimise their experience and outcomes.

Introduction: Medical student training and experiences in nursing homes are often viewed as negative; however, long-term care services represent a growing aspect of our medical system that receives little attention in medical education. The University of New England College of Osteopathic Medicine Learning by Living Nursing Home Immersion Project accelerates students learning about older adult care and the importance of empathy. Methods: Learning by Living applies qualitative ethnographic/autobiographic research methods to answer the question: “What is it like for me to live the life of an older adult nursing home resident?” Two first year medical students (female, 25 y/o & male, 27 y/o) were “admitted” into two different nursing homes for 11 days each. The students were wheelchair reliant from their assigned diagnoses of dominant-side paralysis secondary to stroke and aspiration pneumonia; requiring standard procedures of care experienced by older adults residents with similar conditions. Data were collected in the form of journal notes for pre-fieldwork, fieldwork, and post-fieldwork and included subjective and objective reporting of observations, experiences, and resident encounters. Analyses included journal review and thematic categorization and coding through content analysis. Results: Four themes of significance intersected for the two medical students: 1) control; 2) quality of life; 3) communication; and 4) isolation. Being immersed in nursing home life provided the students with firsthand experiences of loss and challenges faced by nursing home residents. This aided students’ learning about empathy and communication as key components of providing health care. Conclusion: This experience imparted knowledge to the medical students’ about aging, dignity, and the importance of making meaningful connections in order to thrive. These insights provided a gateway to establish a model of patient-centered care that is comprehensive and empathic for the older adult population.

I support the right of local authorities and institutions to impose and police a ban on any “managed” outdoor spaces visited by the public.1 With the indoor ban (which also generated opposition and the constant invocation of “personal freedom”) in place, the air in some public spaces, especially thresholds, is heavily contaminated with cigarette smoke. A ban in outdoor public places would build on the incredible success of the …

Between April 1988 and December 1992, 37 patients with small, previously unirradiated, primary non-small cell carcinomas of the bronchus causing symptoms due to endobronchial disease were treated at the Christie Hospital, Manchester, with a single fraction of high dose rate intraluminal radiotherapy (ILT) using the microSelectron-HDR machine. Small primary (SP) lesions were defined as being less than 2 cm in diameter in a direction perpendicular to the central axis of the iridium-192 treatment source. Fifteen patients (41%) were treated to a dose of 15 Gy and 22 patients (59%) to 20 Gy at a distance of 1 cm from the central axis of the source. At 6 weeks following ILT, improvement in symptoms was seen in the following percentages of patients: haemoptysis 96%, pulmonary collapse 69%, cough 55% and dyspnoea 52%. The magnitude of improvement in these symptoms was largely maintained in patients surviving to 4 months and then 12 months post-ILT. Median actuarial survival was 709 days, 2-year survival 49.4% and 5-year survival 14.1%. Overall, there was no significant difference in survival after treatment with 20 Gy compared with 15 Gy at 1 cm. At the close of study, there were four patients still alive without disease recurrence with survivals of 38, 48, 49 and 63 months. All had had biopsy-proven squamous cell carcinomas and all had been treated with 20 Gy at 1 cm. Five patients died from massive haemoptysis as a terminal event at 4, 9, 9, 10 and 11 months post-ILT, well below the median survival for this group of patients. Again, all had been treated with 20 Gy as opposed to 15 Gy at 1 cm. Over the same time period, 287 patients with non-small cell carcinomas of more than 2 cm in diameter (large primary lesions, LP), were treated with a single fraction of ILT only, as their initial treatment. A consistently greater percentage of patients with SP lesions showed an improvement in the symptoms of haemoptysis and pulmonary collapse when compared with patients with LP lesions. Patients with LP lesions demonstrated a decreased actuarial survival when compared with SP lesions, with median survival being 156 days, 2-year survival 3.1% and no survivors beyond 39 months. This study demonstrates that, in patients with small endobronchial carcinomas a single fraction of ILT can give efficient palliation of symptoms and lead to long term disease-free survival, but that a dose of 20 Gy may be at the limit of bronchial radiation tolerance for a single dose technique employing a high dose rate source.

In April 1988 the Christie Hospital started using the microSelectron-HDR machine to deliver intraluminal radiotherapy (ILT) to inoperable bronchial carcinomas causing symptoms due to endobronchial disease. Results of treatment in the first 406 patients with primary non-small-cell carcinoma are presented. Three main categories of patient were defined. Category 1 consisted of 324 patients (79.8%) who were previously unirradiated and received a single fraction of ILT as their primary treatment, mostly to a dose of 1500 cGy (76%) or 2000 cGy (23%) at 1 cm from the centre of the iridium-192 treatment source. The percentage of these patients whose symptoms or signs were improved at 6 weeks following ILT were as follows: stridor 92%, haemoptysis 88%, cough 62%, dyspnoea, 60%, pain, 50% and pulmonary collapse, 46%. Approximately two-thirds of these patients (67.3%) derived long lasting palliation and required no further treatment during their lifetime. The other third of patients needed subsequent treatment at some stage because of recurrence of their symptoms and in this situation external beam radiotherapy (EB) or a repeat ILT treatment was effectively utilised. Category 2 consisted of 65 patients (16%) who had previously received EB but required ILT when their tumour recurred. At 6 weeks post-ILT levels of symptom palliation were broadly similar to those obtained if ILT was used in previously unirradiated individuals, although the improvement was not so well sustained with time and only 7% showed improvement in pulmonary collapse at 6 weeks. Category 3 consisted of 17 patients (4.2%) in whom ILT was used concurrently with EB as a combined initial treatment. Similar levels of palliation were seen when compared with patients who received a single ILT treatment only. Overall, ILT was well tolerated in terms of early and late morbidity. In conclusion, the efficiency of a single ILT treatment in palliating symptoms due to endobronchial tumour in previously unirradiated individuals is comparable with that reported in series where treatment for advanced lung cancer combines a prolonged course of EB concurrently with several ILT treatments.

Fifty patients with inoperable, symptomatic endobronchial carcinoma were treated by a single exposure of intraluminal radiotherapy. A high dose rate afterloading system (the micro-Selectron-HDR) was used to minimise radiation exposure for staff. Haemoptysis was relieved in 24 of 28 patients, breathlessness in 21 of 33 patients, and cough in nine of 18 patients. Radiological collapse resolved in 11 of 24 patients. Treatment was given on an outpatient basis and was well tolerated. Intraluminal radiotherapy appears to offer an effective alternative to conventional fractionated external beam radiotherapy.

The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit.

Epidermal growth factor receptor (EGF-R) expression was assessed in 63 lung tumour samples with a monoclonal antibody (EGF-R1) by indirect immunoperoxidase staining on cryostat sections. All 15 small cell lung cancer samples were negative whereas over 80% of the 48 non small lung cancer stained positively. In 30 bronchial biopsies two monoclonal antibodies against the cytoplasmic part of the EGF-R were evaluated. These antibodies showed weaker staining than EGF-R1. No additional or enhanced staining as compared with EGF-R1 was observed, suggesting a lack of enhanced expression of a truncated EGF-R analogous to the v-erb-B oncogene product. Monoclonal antibodies against the EGF-R may be helpful diagnostically in differentiating small cell from non small cell lung cancer and may also be important in elucidating biological differences in primary lung cancer. Images Figure 2

One hundred sixty-three patients with small cell lung cancer were treated with six courses, at 3-week intervals, of ifosfamide (5 g/m2) with mesna and etoposide. Thoracic radiotherapy was delivered to the limited stage (LS) patients. The complete response rate (CR, determined clinically and radiologically) was 76% for the 78 LS patients with a further 14% partial response (PR). The majority of the CRs were confirmed on a follow-up bronchoscopy. The CR rate was 27% for extensive stage (ES) patients with another 38% undergoing a partial response. The median survival for LS patients was 11 months, (16 months for CR confirmed by rebronchoscopy) and 8 months for ES patients. The 2-year actuarial survival for LS patients is 27%, follow-up ranges from 12 months to 30 months with a median of 22 months. Toxicity was not severe for the patient population, of whom only 20% had a good performance status before chemotherapy. Parental antibiotics were required on 4% of all 844 chemotherapy courses and 12% of courses were delayed due to side effects. The majority of responses occurred within the first two courses of chemotherapy and there was a corresponding improvement in the patients' symptoms and performance status. The regimen produced rapid tumor response with corresponding improvement in symptoms without marked toxicity and allowed further treatment development.

Thirty-nine patients with histologically proven widely metastatic bronchogenic carcinoma were treated with cyclophosphamide and Corynebacterium parvum. The dosage of cyclophosphamide was higher than conventional as previous work had indicated better results with increased dosage. Experimental work had suggested that the addition of Corynebacterium parvum would increase the antitumour effect and possibly reduce the cyclophosphamide induced granulocytopenia. A short treatment programme using three i.v. injections of cyclophosphamide, 1.5 g/m2, 2.5 g/m2 then 3.5 g/m2, at 3 week intervals were given. Four days after each cyclophosphamide injection, C. parvum 2 mg/m2 i.v. was administered. An overall 38% tumour response rate was observed, 18% for patients with non-small-cell carcinoma and 65% for small-cell carcinoma patients. The median survival for the 39 patients was 5 months (range 1-16+ months). These results, particularly for the non-small-cell patient group are comparable to those obtained with intensive combination chemotherapy regimens administered intermittently over much longer periods. An important consideration, objectively assessed in the present study, was the effect of treatment on quality of life and breathlessness. Improvement was noted not only in those patients with tumour response but also in a proportion of those who did not fulfil the criteria of response. Toxicity was also carefully assessed and, although the cyclophosphamide dosages were higher than conventionally used, no undue problems were noted. The addition of C. parvum did not have any noticeable beneficial effect. Cyclophosphamide given at dosages higher than is usual but which do not require bone marrow rescue is worthy of further study.

Metastasis to the lung occurs quite commonly from certain types of extrapulmonary primary carcinoma. Spread to the bronchial lumen is relatively rare. When this does occur, symptoms resembling those of primary bronchial carcinoma are often present, in association with partial or complete obstruction of the bronchial lumen. Palliation of such symptoms is possible with the use of intraluminal radiotherapy (ILT). Between 1990 and 1998, 37 patients with endobronchial metastases were treated using this modality; a single fraction of radiation was delivered by the remote afterloading high dose rate microSelectron system. Data regarding these patients' characteristics and outcome are presented, following a retrospective review of case notes. The commonest symptoms were dyspnoea, cough and haemoptysis; the commonest primary tumour sites were breast, colorectum, oesophagus and kidney. Twenty-four (64·9%) patients had some improvement in symptoms following treatment. Mean overall survival was 280 days, range 9–1145 days. No serious adverse effects occurred. ILT is a relatively simple, safe and effective treatment in the palliation of symptoms due to endobronchial metastases.