Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial.

BACKGROUND: Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma. METHODS: This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 1010 viral particles administered by 5·00 × 107 NSCs, the second cohort a dose of 1·25 × 1011 viral particles administered by 1·00 × 108 NSCs, and the third cohort a dose of 1·875 × 1011 viral particles administered by 1·50 × 108 NSCs. No further dose escalation was planned. Within 10-14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134. FINDINGS: Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 108 NSCs loading 1·875 × 1011 viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 108 NSCs loading 1·875 × 1011 viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5-not reached) and median overall survival was 18·4 months (15·7-not reached). INTERPRETATION: NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial. FUNDING: US National Institutes of Health.

Just-in-Time Training for High-Risk Low-Volume Therapies: An Approach to Ensure Patient Safety.

High-risk low-volume therapies are those therapies that are practiced infrequently and yet carry an increased risk to patients because of their complexity. Staff nurses are required to competently manage these therapies to treat patients' unique needs and optimize outcomes; however, maintaining competence is challenging. This article describes implementation of Just-in-Time Training, which requires validation of minimum competency of bedside nurses managing high-risk low-volume therapies through direct observation of a return-demonstration competency checklist.

Australian academic primary health-care careers: a scoping survey.

This study was undertaken to provide a snapshot of the academic primary health-care workforce in Australia and to provide some insight into research capacity in academic primary health care following changes to funding for this sector. A convenience sample of individuals self-identifying as working within academic primary health care (n=405) completed an anonymous online survey. Respondents were identified from several academic primary health-care mailing lists. The survey explored workforce demographics, clarity of career pathways, career trajectories and enablers/barriers to 'getting in' and 'getting on'. A mix of early career (41%), mid-career (25%) and senior academics (35%) responded. Early career academics tended to be female and younger than mid-career and senior academics, who tended to be male and working in 'balanced' (teaching and research) roles and listing medicine as their disciplinary background. Almost three-quarters (74%) indicated career pathways were either 'completely' or 'somewhat unclear', irrespective of gender and disciplinary backgrounds. Just over half (51%) had a permanent position. Males were more likely to have permanent positions, as were those with a medical background. Less than half (43%) reported having a mentor, and of the 57% without a mentor, more than two-thirds (69%) would like one. These results suggest a lack of clarity in career paths, uncertainty in employment and a large number of temporary (contract) or casual positions represent barriers to sustainable careers in academic primary health care, especially for women who are from non-medicine backgrounds. Professional development or a mentoring program for primary health-care academics was desired and may address some of the issues identified by survey respondents.

Investigating the sustainability of careers in academic primary care: a UK survey.

BACKGROUND: The UK National Health Service (NHS) is undergoing institutional reorganisation due to the Health and Social Care Act-2012 with a continued restriction on funding within the NHS and clinically focused academic institutions. The UK Society for Academic Primary Care (SAPC) is examining the sustainability of academic primary care careers within this climate and preliminary qualitative work has highlighted individual and organisational barriers. This study seeks to quantify the current situation for academics within primary care. METHODS: A survey of academic primary care staff was undertaken. Fifty-three academic primary care departments were selected. Members were invited to complete a survey which contained questions about an individual's career, clarity of career pathways, organisational culture, and general experience of working within the area. Data were analysed descriptively with cross-tabulations between survey responses and career position (early, mid-level, senior), disciplinary background (medical, scientist), and gender. Pearson chi-square test was used to determine likelihood that any observed difference between the sets arose by chance. RESULTS: Responses were received from 217 people. Career pathways were unclear for the majority of people (64%) and 43% of the workforce felt that the next step in their career was unclear. This was higher in women (52% vs. men 25%; χ(2)(3) = 14.76; p = 0.002) and higher in those in early career (50% vs. senior career, 25%) and mid-career(45%; vs. senior career; χ(2)(6) = 29.19, p < 0.001). The workforce appeared geographically static but unstable with only 50% of people having their contract renewed or extended. The majority of people (59%) have never been promoted by their institution. There were perceptions of gender equality even in the context of females being underrepresented in senior positions (19% vs. males 39%; χ(2)(3) = 8.43, p = 0.015). Despite these findings, the majority of the workforce reported positive organisational and cultural experiences. CONCLUSIONS: Sustainability of a academic primary care career is undermined by unclear pathways and a lack of promotion. If the discipline is to thrive, there is a need to support early and mid-career individuals via greater transparency of career pathways. Despite these findings staff remained positive about their careers.

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare.

BACKGROUND: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. METHODS: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. RESULTS: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patient-caregiver interaction, self-care and metabolic transmission were reported for some communication technologies. CONCLUSIONS: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals.

Habituation of the Light-Startle Response of Orange Head Cockroaches (Eublaberus posticus): Effects of Acclimation, Stimulus Duration, Presence of Food, and Intertrial Interval.

The purpose of this paper is to establish the orange head cockroach (Eublaberus posticus) as a useful insect subject for research in comparative psychology by investigating habituation of the light-startle response (LSR). While one goal of comparative psychology is to compare the behavior of a diversity of species, many taxa, including cockroaches, are grossly underrepresented. Our work serves to improve this deficit by investigating habituation learning in the orange head cockroach in four experiments. In our first experiment, we found that LSR, and habituation of LSR, occurs to both lights being turned on and lights being turned off. In our second experiment, we found that the duration of a light did not affect response, and that spontaneous recovery of LSR occurs after 24 h intervals. In our third experiment, we found that the presence of food inhibited LSR. In our final experiment, we found that the rate of LSR habituation decreased as intertrial interval increased, in a manner predicted by established principles of habituation. Our work lays a strong foundation for future research on the behavior of orange head cockroaches as well as learning in cockroaches in general. We hope that our findings help establish cockroaches as practical insect subjects for research in comparative psychology and related fields such as behavior analysis and behavioral ecology.

A first-in-human phase 0 clinical study of RNA interference-based spherical nucleic acids in patients with recurrent glioblastoma.

Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference-based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial (NCT03020017) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment-related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129-treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.

It's about time: physicians' perceptions of time constraints in primary care medical practice in three national healthcare systems.

BACKGROUND: As physicians are pressured to deliver an increasing number of preventive services, follow guidelines, engage in evidence-based practice, and deliver patient-centered care in managerially driven organizations, they struggle with how much control they have over their time. METHODS: A secondary analysis was conducted with data from 3 parallel studies of clinical decision making in Germany, the United Kingdom, and the United States with 128 physicians per country. Physicians reported how much time they were allocated and how much time they needed for high-quality care for new patient appointments, routine consultations, and complete physicals. They also reported how much control they had over their time in the office and spending adequate time with patients. RESULTS: German, British, and American physicians were allocated (on average) 16/11/32 minutes for a new patient appointment, 6/10/18 minutes for a routine visit, and 12/20/36 minutes for a complete physical, but felt that they needed more time. Over half of German and American physicians felt that they always or usually had control over the hours they were required to be in their office or spending sufficient time with their patients while less than half of British physicians felt this way. CONCLUSION: German physicians had the least time allocated and needed for most types of appointment. American physicians had the most time allocated and needed for each type of appointment. However, British physicians felt they had the least control over time in their office and spending sufficient time with patients.

Women and men with coronary heart disease in three countries: are they treated differently?

BACKGROUND: Nonmedical determinants of medical decision making were investigated in an international research project in the United States, the United Kingdom, and Germany. The key question in this paper is whether and to what extent doctors' diagnostic and therapeutic decisions in coronary heart disease (CHD) are influenced by patient gender. METHODS: A factorial experiment with a videotaped patient consultation was conducted. Professional actors played the role of patients with symptoms of CHD. Several alternative versions were taped featuring the same script with patient-actors of different gender, age, race, and socioeconomic status. The videotapes were presented to a randomly selected sample of 128 primary care physicians in each country. Using an interview with standardized and open-ended questions, physicians were asked how they would diagnose and treat such a patient after they had seen the video. RESULTS: Results show gender differences in the diagnostic strategies of the doctors. Women were asked different questions, CHD was mentioned more often as a possible diagnosis for men than for women, and physicians were less certain about their diagnosis with female patients. Gender differences in management decisions (therapy and lifestyle advice) are less pronounced and less consistent than in diagnostic decisions. Magnitude of gender effect on doctors' decisions varies between countries with smaller influences in the United States. CONCLUSION: Although patients with identical symptoms were presented, primary care doctors' behavior differed by patients' gender in all 3 countries under study. These gender differences suggest that women may be less likely to receive an accurate diagnosis and appropriate treatment than men.

Country differences in the diagnosis and management of coronary heart disease - a comparison between the US, the UK and Germany.

BACKGROUND: The way patients with coronary heart disease (CHD) are treated is partly determined by non-medical factors. There is a solid body of evidence that patient and physician characteristics influence doctors' management decisions. Relatively little is known about the role of structural issues in the decision making process. This study focuses on the question whether doctors' diagnostic and therapeutic decisions are influenced by the health care system in which they take place. This non-medical determinant of medical decision-making was investigated in an international research project in the US, the UK and Germany. METHODS: Videotaped patients within an experimental study design were used. Experienced actors played the role of patients with symptoms of CHD. Several alternative versions were taped featuring the same script with patients of different sex, age and social status. The videotapes were shown to 384 randomly selected primary care physicians in the three countries under study. The sample was stratified on gender and duration of professional experience. Physicians were asked how they would diagnose and manage the patient after watching the video vignette using a questionnaire with standardised and open-ended questions. RESULTS: Results show only small differences in decision making between British and American physicians in essential aspects of care. About 90% of the UK and US doctors identified CHD as one of the possible diagnoses. Further similarities were found in test ordering and lifestyle advice. Some differences between the US and UK were found in the certainty of the diagnoses, prescribed medications and referral behaviour. There are numerous significant differences between Germany and the other two countries. German physicians would ask fewer questions, they would order fewer tests, prescribe fewer medications and give less lifestyle advice. CONCLUSION: Although all physicians in the three countries under study were presented exactly the same patient, some disparities in the diagnostic and patient management decisions were evident. Since other possible influences on doctors treatment decisions are controlled within the experimental design, characteristics of the health care system seem to be a crucial factor within the decision making process.

Art museum-based intervention to promote emotional well-being and improve quality of life in people with dementia: The ARTEMIS project.

ARTEMIS (ART Encounters: Museum Intervention Study) is an art-based intervention designed especially for people with dementia and their care partners that involves a combination of museum visits and artistic activity. This paper reports the results of a randomized wait-list controlled study on the influence of the ARTEMIS intervention on the emotional state, well-being, and quality of life of dementia patients. People with mild-to-moderate dementia (n = 44) and their care partners (n = 44) visited the Frankfurt Städel Museum once a week on six pre-arranged occasions. The intervention consisted of six different guided art tours (60 minutes), followed by art-making in the studio (60 minutes). Independent museum visits served as a control condition. A mixed-methods design was used to assess several outcomes including cognitive status, emotional well-being, self-rated aspects of quality of life, and subjective evaluations by informal caregivers. In a pre-post-assessment, we found significant improvements in participants' self-rated quality of life (t = -3.15, p < .05). In a situational assessment of emotional well-being immediately before and after each of the museum sessions, we were able to demonstrate statistically significant positive changes with medium effect sizes (dcorr = .74-.77). Furthermore, the total Neuropsychiatric Inventory score as well as the affective (depressed mood and anxiety) and apathy subscales were significantly lower after the ARTEMIS intervention (tNPI total = 2.43; tNPI affective = 2.24; tNPI apathy = 2.52; p < .05). The results show that art museum-based art interventions are able to improve the subjective well-being, mood, and quality of life in people with dementia. This promising psychosocial approach deserves further attention in future studies and consideration in community-based dementia care programs.

Report of the Key Opinion Leaders Meeting on Stem Cell-derived Beta Cells.

Beta cell replacement has the potential to restore euglycemia in patients with insulin-dependent diabetes. Although great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association in collaboration with the Harvard Stem Cell Institute, the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells. The following summary highlights current technology, recent significant breakthroughs, unmet needs and roadblocks to stem cell-derived beta cell therapies, with the aim of spurring future preclinical collaborative investigations and progress toward the clinical application of stem cell-derived beta cells.

Barriers to the use of e-health technology in nurse practitioner-patient consultations.

PURPOSE: This paper examines primary care nurse practitioners' (NPs') use of information available via e-health technology (EHT) within consultations. It explores which information resources NPs use in clinical decision making, their comparative use of electronic versus paper-based and human information resources, the reasons behind their choices and how the use of different resources impacts on patient interactions. METHODS: Semi-structured interviews were undertaken with 12 NPs recruited from 11 different general practitioner (GP) practices and five primary care trusts (PCTs) within the West Midlands South Strategic Health Authority, UK. FINDINGS: The key finding was that for NPs an effective information resource is one that provides sufficient information to generate a patient management plan rapidly. Speed, familiarity and trust are vital ingredients for regular use. Paper-based information resources therefore retain a significant role, and together with human information resources are still more frequently used than most electronic, and particularly web-based, resources. The latter are not yet well established within the context of patient consultations. Electronic clinical support systems (such as Mentor, Prodigy and GPnotebook) are regularly used, however, because they are often linked electronically to patient records, and generate brief information in a form accessible to both nurses and patients. By contrast, searching for information from web-based resources was considered time-consuming, technically difficult and disruptive to patients. All NPs reported some negative effects on patients of using computers: mostly disrupted rapport and longer consultations. However, the majority had developed ways of working to overcome these difficulties and that helped them to maintain their patient-centred focus. CONCLUSIONS: Study NPs had received only very limited information technology (IT) training, but nevertheless were enthusiastic about computer use. This suggests that with further training they could adapt their practice to embrace more EHT, which would enhance their ability to be more autonomous and to base their practice on sound clinical evidence.

How do doctors in different countries manage the same patient? Results of a factorial experiment.

OBJECTIVE: To determine the relative contributions of: (1) patient attributes; (2) provider characteristics; and (3) health care systems to health care disparities in the management of coronary heart disease (CHD) and depression. DATA SOURCES/STUDY SETTING: Primary experimental data were collected in 2001-2 from 256 randomly sampled primary care providers in the U.S. (Massachusetts) and the U.K. (Surrey, Southeast London, and the West Midlands). STUDY DESIGN: Two factorial experiments were conducted in which physicians were shown, in random order, two clinically authentic videotapes of "patients" presenting with symptoms strongly suggestive of CHD and depression. "Patient" characteristics (age, gender, race, and socioeconomic status [SES]) were systematically varied, permitting estimation of unconfounded main effects and the interaction of patient, provider, and system-level influences. DATA COLLECTION/DATA EXTRACTION METHODS: Analysis of variance was used to measure provider decision-making outcomes, including diagnosis, information seeking, test ordering, prescribing behavior, lifestyle recommendations, and referrals/follow-ups. PRINCIPAL FINDINGS: There is a high level of consistency in decision making for CHD and depression between the U.S. and the U.K. Most physicians in both countries correctly identified conditions depicted in the vignettes, although U.S. doctors engage in more information seeking, are more likely to prescribe medications, and are more certain of their diagnoses than their U.K. counterparts. The absence of any national differences in test ordering is consistent for both of the medical conditions depicted. U.K. physicians, however, were more likely than U.S. physicians to make lifestyle recommendations for CHD and to refer those patients to other providers. CONCLUSIONS: Substantively, these findings point to the importance of patient and provider characteristics in understanding between-country differences in clinical decision making. Methodologically, our use of a factorial experiment highlights the potential of these methods for health services research-especially the estimation of the influence of patient attributes, provider characteristics, and between-country differences in the quality of medical care.

Patient characteristics and inequalities in doctors' diagnostic and management strategies relating to CHD: a video-simulation experiment.

Numerous studies examine inequalities in health by gender, age, class and race, but few address the actions of primary care doctors. This factorial experiment examined how four patient characteristics impact on primary care doctors' decisions regarding coronary heart disease (CHD). Primary care doctors viewed a video-vignette of a scripted consultation where the patient presented with standardised symptoms of CHD. Videotapes were identical apart from varying patients' gender, age (55 versus 75), class and race, thereby removing any confounding factors from the social context of the consultation or other aspects of patients' symptomatology or behaviour. A probability sample of 256 primary care doctors in the UK and US viewed these video-vignettes in a randomised experimental design. Gender of patient significantly influenced doctors' diagnostic and management activities. However, there was no influence of social class or race, and no evidence of ageism in doctors' behaviour. Women were asked fewer questions, received fewer examinations and had fewer diagnostic tests ordered for CHD. 'Gendered ageism' was suggested, since midlife women were asked fewest questions and prescribed least medication appropriate for CHD. Primary care doctors' behaviour differed significantly by patients' gender, suggesting doctors' actions may contribute to gender inequalities in health.

A new simple six-step model to promote recruitment to RCTs was developed and successfully implemented.

OBJECTIVES: How a randomized controlled trial (RCT) is explained to patients is a key determinant of recruitment to that trial. This study developed and implemented a simple six-step model to fully inform patients and to support them in deciding whether to take part or not. STUDY DESIGN AND SETTING: Ninety-two consultations with 60 new patients were recorded and analyzed during a pilot RCT comparing surgical and nonsurgical interventions for hip impingement. Recordings were analyzed using techniques of thematic analysis and focused conversation analysis. RESULTS: Early findings supported the development of a simple six-step model to provide a framework for good recruitment practice. Model steps are as follows: (1) explain the condition, (2) reassure patients about receiving treatment, (3) establish uncertainty, (4) explain the study purpose, (5) give a balanced view of treatments, and (6) Explain study procedures. There are also two elements throughout the consultation: (1) responding to patients' concerns and (2) showing confidence. The pilot study was successful, with 70% (n = 60) of patients approached across nine centers agreeing to take part in the RCT, so that the full-scale trial was funded. CONCLUSION: The six-step model provides a promising framework for successful recruitment to RCTs. Further testing of the model is now required.

UK FASHIoN: feasibility study of a randomised controlled trial of arthroscopic surgery for hip impingement compared with best conservative care.

BACKGROUND: Femoroacetabular impingement (FAI) is a syndrome of hip or groin pain associated with shape abnormalities of the hip joint. Treatments include arthroscopic surgery and conservative care. This study explored the feasibility of a randomised controlled trial to compare these treatments. OBJECTIVES: The objectives of this study were to estimate the number of patients available for a full randomised controlled trial (RCT); to explore clinician and patient willingness to participate in such a RCT; to develop consensus on eligibility criteria, surgical and best conservative care protocols; to examine possible outcome measures and estimate the sample size for a full RCT; and to develop trial procedures and estimate recruitment and follow-up rates. METHODS: Pre-pilot work: we surveyed all UK NHS hospital trusts (n = 197) to identify all FAI surgeons and to estimate how much arthroscopic FAI surgery they performed. We interviewed a purposive sample of 18 patients, 36 physiotherapists, 18 surgeons and two sports physicians to explore attitudes towards a RCT and used consensus-building methods among them to develop treatment protocols and patient information. Pilot RCT: we performed a pilot RCT in 10 hospital trusts. Patients were randomised to receive either hip arthroscopy or best conservative care and then followed up at 3, 6 and 12 months using patient-reported questionnaires for hip pain and function, activity level, quality of life, and a resource-use questionnaire. Qualitative recruitment intervention: we performed semistructured interviews with all researchers and clinicians involved in the pilot RCT in eight hospital trusts and recorded and analysed diagnostic and recruitment consultations with eligible patients. RESULTS: We identified 120 surgeons who reported treating at least 1908 patients with FAI by hip arthroscopy in the NHS in the financial year 2011/12. There were 34 hospital trusts that performed ≥ 20 arthroscopic FAI operations in the year. We found that clinicians were positive about a RCT: only half reported equipoise, but most said that they would be prepared to randomise patients. Patients strongly supported a RCT, but expressed concerns about its design; these were used to develop patient information for the pilot RCT. We developed a surgical protocol and showed that this could be used in a RCT. We developed a physiotherapy-led exercise-based package of best conservative care called 'personalised hip therapy' and showed that this was practicable. In the pilot RCT, we recruited 42 out of 60 eligible patients (70%) across nine sites. The mean duration and recruitment rate across all sites were 4.5 months and one patient per site per month, respectively. The lead site recruited for the longest period (9.3 months) and accrued the largest number of patients (2.1 patients per month). We recorded and analysed 84 diagnostic and recruitment consultations in 60 patients and used these to develop a model for an optimal recruitment consultation. We identified the International Hip Outcome Tool at 12 months as an appropriate outcome measure and estimated the sample size for a full trial as 344 participants: a number that could be recruited in 25 centres over 18 months. CONCLUSION: We have demonstrated that it is feasible to perform a RCT to establish the clinical effectiveness of hip arthroscopy compared with best conservative care for FAI. We have designed a full trial and developed and tested procedures for it, including an innovative approach to recruitment. We propose that a full trial be implemented. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Survival of Anisakis simplex in arrowtooth flounder (Atheresthes stomia) during frozen storage.

Survival of naturally occurring larvae of Anisakis simplex in fresh arrowtooth flounder (Atheresthes stomia) was determined after storage for specified periods at four freezing temperatures. All larvae were killed by 96, 60, 12, and 9 h at temperatures of -15, -20, -30, and -40 degrees C, respectively. The average percentages of live larvae per fillet at the next shortest holding time were as follows: 72 h at -15 degrees C, 0 to 3%; 48 h at -20 degrees C, 11 to 30%; 9 h at -30 degrees C, 5%; and 6 h at -40 degrees C, 0 to 3%. Larval survival was directly related to fillet thickness or weight (P < or = 0.05). Larval death was directly correlated to freezing temperatures. Holding time necessary to kill larval nematodes decreased as storage temperature decreased.

Population dynamics of the philometrid nematode Margolisianum bulbosum in the southern flounder Paralichthys lethostigma (Pisces: Paralichthyidae) in South Carolina, USA.

This is the first report of the philometrid nematode Margolisianum bulbosum Blaylock and Overstreet, 1999 from the southern flounder Paralichthys lethostigma on the east coast of the USA. Observation of adult female worms was used as an indication of the parasite's presence in the fish. Adult females were found only in P. lethostigma >50 mm total length. The overall prevalence was 74%, with a mean intensity of 5 female nematodes per parasitized fish. Infected flounders were found throughout the year with a statistically significant decrease in intensity in the winter months. Neither salinity, water temperature, fish gender nor fish age were found to influence either prevalence or intensity of infection in the flounder. While larvigerous (gravid) females were found throughout the year, the significant decrease in their occurrence during the summer through fall, in concert with an observed decrease in intensity of infection during the winter, indicated that the life cycle of this philometrid species is likely to be annual.