Studying a disease with no home - lessons in trial recruitment from the PATCH II study

<p>Abstract</p> <p>Background</p> <p>Cellulitis is a very common condition that often recurs. The PATCH II study was designed to explore the possibility of preventing future episodes of cellulitis, with resultant cost savings for the NHS. This was the first trial to be undertaken by the UK Dermatology Clinical Trials Network. As such, it was the first to test a recruitment model that involved many busy clinicians each contributing just a few patients.</p> <p>Methods</p> <p>A double-blind randomised controlled trial comparing prophylactic antibiotics (penicillin V) with placebo tablets, for the prevention of repeat episodes of cellulitis of the leg. Primary outcome was time to subsequent recurrence of cellulitis.</p> <p>Results</p> <p>The PATCH II study was closed to recruitment having enrolled 123 participants from a target of 400. Whilst the recruitment period was extended by 12 months, it was not possible to continue beyond this point without additional funds. Many factors contributed to poor recruitment: (i) changes in hospital policy and the introduction of community-based intravenous teams resulted in fewer cellulitis patients being admitted to hospital; ii) those who were admitted were seen by many different specialties, making it difficult for a network of dermatology clinicians to identify suitable participants; and iii) funding for research staff was limited to a trial manager and a trial administrator at the co-ordinating centre. With no dedicated research nurses at the recruiting centres, it was extremely difficult to maintain momentum and interest in the study. Attempts to boost recruitment by providing some financial support for principal investigators to employ local research staff was of limited success.</p> <p>Discussion</p> <p>The model of a network of busy NHS clinicians all recruiting a few patients into large clinical studies requires further testing. It did not work very well for PATCH II, but this was probably because patients were not routinely seen by dermatologists, and recruitment took place prior to research support being available through the Comprehensive Clinical Research Network (CCRN). There is a balance to be struck between asking a lot of centres to recruit just a few patients, and asking a few centres to recruit a lot of patients. Giving modest funds to principal investigators to buy local research nurse time did not work well, probably because too little research time was bought, and it was difficult to separate research tasks from the nurses existing clinical duties. National research infrastructure networks such as the Comprehensive Clinical Research Network will overcome many of the problems encountered in the PATCH II trial.</p> <p>Trial Registration</p> <p>The trial registration number is ISRCTN03813200.</p

Magnetic resonance imaging of the knee in Norway 2002–2004 (national survey): rapid increase, older patients, large geographic differences

<p>Abstract</p> <p>Background</p> <p>Magnetic resonance imaging (MRI) of the knee is the second most common MRI examination in Norway after head/brain MRI. Little has been published internationally on trends in the use of knee MRI after 1999. This study aimed to describe levels and trends in ambulant knee MRI utilisation in Norway 2002–2004 in relation to type of radiology service, geographic regions, number of MRI-scanners, patient age and gender, and type of referring health care provider.</p> <p>Methods</p> <p>We analysed administrative data on all claims for reimbursement of ambulant knee MRI performed in Norway in 2002, 2003 and 2004 and noted nominal reimbursement. We also recorded the referring health care provider from clinical requests of ambulant knee MRI done consecutively during two months in 2004 at one private institute and three hospitals. Number of MRI-scanners was given by manufacturers and radiology services.</p> <p>Results</p> <p>In Norway, the rate of knee MRI claims for 2004 was 15.6 per 1000 persons. This rate was 74% higher in East than in North region (18.4 vs. 10.6), slightly higher for men than women (16.4 vs. 14.7) and highest for ages 50–59 years (29.0) and 60–69 years (21.2). Most claims (76% for 2004) came from private radiology services. In 2004, the referring health care provider was a general practitioner in 63% of claims (unspecified in 24%) and in 83.5% (394/472) of clinical requests. From 2002 to 2004, the rate of knee MRI claims increased 64%. In the age group 50 years or above the increase was 86%. Rate of MRI-scanners increased 43% to 21 scanners per million persons in 2004. Reimbursement for knee MRI claims (nominal value) increased 80% to 70 million Norwegian kroner in 2004.</p> <p>Conclusion</p> <p>Ambulant knee MRI utilisation in Norway increases rapidly especially for patients over 50, and shows large geographic differences. Evaluation of clinical outcomes of this activity is needed together with clinical guidelines for use of knee MRI.</p

Cost-effectiveness of general practice care for low back pain: a systematic review

Care from a general practitioner (GP) is one of the most frequently utilised healthcare services for people with low back pain and only a small proportion of those with low back pain who seek care from a GP are referred to other services. The aim of this systematic review was to evaluate the evidence on cost-effectiveness of GP care in non-specific low back pain. We searched clinical and economic electronic databases, and the reference list of relevant systematic reviews and included studies to June 2010. Economic evaluations conducted alongside randomised controlled trials with at least one GP care arm were eligible for inclusion. Two reviewers independently screened search results and extracted data. Eleven studies were included; the majority of which conducted a cost-effectiveness or cost-utility analysis. Most studies investigated the cost-effectiveness of usual GP care. Adding advice, education and exercise, or exercise and behavioural counselling, to usual GP care was more cost-effective than usual GP care alone. Clinical rehabilitation and/or occupational intervention, and acupuncture were more cost-effective than usual GP care. One study investigated the cost-effectiveness of guideline-based GP care, and found that adding exercise and/or spinal manipulation was more cost-effective than guideline-based GP care alone. In conclusion, GP care alone did not appear to be the most cost-effective treatment option for low back pain. GPs can improve the cost-effectiveness of their treatment by referring their patients for additional services, such as advice and exercise, or by providing the services themselves

An examination of the long-term business value of investments in information technology

In this paper, we examine the effects of investments in Information Technology (IT) on the long term business values of organizations. The regression discontinuity design is used in this research to examine eight hundred and ten IT investment announcements collected from the period 1982–2007. Our results found that press releases can affect the market value of a firm by possibly providing investors with a better idea of a firm’s current and future operations and strategy. On the other hand, these press releases also appear to attract more transient investors. The attraction of transient investors likely suggests the market believes the IT investing firm is serious about its potential for growth and expansion

Postpartum psychiatric disorders

Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential

Management of adults with primary frozen shoulder in secondary care (UK FROST): a multicentre, pragmatic, three-arm, superiority randomised clinical trial

Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection. In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508. Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release). All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective. The National Institute for Health Research Health Technology Assessment programme. [Abstract copyright: Copyright © 2020 The Author(s). Publishedx by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Cell death during sepsis: integration of disintegration in the inflammatory response to overwhelming infection

Sepsis is a major health problem and a leading cause of death worldwide. In recent years, a crescendo of attention has been directed to the mechanisms of cell death that develop during this disease, since these are viewed as important contributors to the proinflammatory and anti-inflammatory responses associated with poor outcome. Here we discuss mechanisms of cell death evident severe bacterial infection and sepsis including necrosis, apoptosis, pyroptosis, and extracellular trap-associated neutrophil death, with a particular emphasis on lymphocyte apoptosis and its contribution to the immunosuppressed phenotype of late sepsis. Individual bacterial pathogens express virulence factors that modulate cell death pathways and influence the sepsis phenotype. A greater knowledge of cell death pathways in sepsis informs the potential for future therapies designed to ameliorate immune dysfunction in this syndrome

Cost-effectiveness of surgery versus cast immobilization for adults with a bicortical fracture of the scaphoid waist: an economic evaluation of the SWIFFT trial

Aims The aim of the Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) was to determine the optimal treatment for adults with a bicortical undisplaced or minimally displaced fracture of the waist of the scaphoid, comparing early surgical fixation with initial cast immobilization, with immediate fixation being offered to patients with nonunion. Methods A cost-effectiveness analysis was conducted to assess the relative merits of these forms of treatment. The differences in costs to the healthcare system and quality-adjusted life years (QALYs) of the patients over the one-year follow-up of the trial in the two treatment arms were estimated using regression analysis. Results Our base case analysis found that patients randomized to early surgical fixation had statistically significantly higher mean costs to the NHS of £1,295 more than for the cast immobilization arm (p < 0.001), primarily due to the cost of surgery. They also had a marginally better quality of life, over the period, of 0.0158 QALYs; however, this was not statistically significant (p = 0.379). The mean combined cost per additional QALY was £81,962, well above the accepted threshold for cost-effectiveness used in the UK and internationally. The probability of early surgery being cost-effective in this setting was only 5.6%. Conclusion Consistent with the clinical findings of SWIFFT, these results indicate that initial cast immobilization of minimally displaced scaphoid fractures, with immediate fixation only offered to patients with nonunion, is the optimal form of treatment, resulting in comparable outcomes with less cost to the healthcare system