Design and intermediate results of the Lower Extremity Arterial Disease Event Reduction (LEADER)* trial of bezafibrate in men with lower extremity arterial disease [ISRCTN41194621]

BACKGROUND: Raised levels of both triglycerides and fibrinogen, each of which are reduced by bezafibrate, may contribute to lower extremity arterial disease (LEAD). This condition is characterized by a particularly high incidence of coronary heart disease (CHD) and stroke, but is little studied thus far in randomised controlled trials. METHOD: Patients were recruited through 85 practices in the British Medical Research Council General Practice Research Framework and through nine hospital vascular clinics. The treatment regimen, which is double-blind and placebo-controlled, is bezafibrate 400 mg/day. The 1568 patients recruited represent 86% of those eligible at screening. RESULTS: None of the anticipated side effects (mainly gastrointestinal) differed between the two groups. Nearly 80% of the total person-years accrued at 3 years were spent on trial treatment. Bezafibrate significantly reduced total cholesterol by approximately 8.0% and low-density lipoprotein (LDL)-cholesterol by approximately 9.0%, and increased high-density lipoprotein (HDL)-cholesterol by approximately 11.0% initially, falling to about 6.0% at 3 years. Triglycerides were significantly reduced by about 23.0% and fibrinogen by about 14.0%. Plasma creatinine rose by approximately 11% in those on active treatment. All of these effects were highly significant (P < 0.0001). Bezafibrate had no effect on the level of C-reactive protein (CRP). CONCLUSION: The trial recruited an unusually high proportion of eligible patients, ensuring the general applicability of its results. The fibrinogen-lowering and lipid-modifying effects of bezafibrate were confirmed. Although bezafibrate lowers fibrinogen, it has no effect on CRP; this suggests that the reduction in fibrinogen is due to an effect on its metabolism rather than suppression of an inflammatory response

Association between ultrasound assessment of glenohumeral subluxation and shoulder pain, muscle strength, active range of movement and upper limb function in people with stroke

Background: Glenohumeral subluxation (GHS) is a commonly reported post-stroke complication which has a negative effect on rehabilitation. Objective: To explore the association between GHS and other clinical outcomes in people with post-stroke hemiplegia. Methods: Patients with post-stroke hemiplegia (n=105, 71±11 years, median time since stroke 5.6 weeks), who gave informed consent, were recruited. GHS was assessed by the ultrasound method. Assessment of shoulder pain (visual analogue scale), active range of movement (AROM), muscle strength (Medical Research Council Scale), muscle tone (Modified Ashworth Scale) and the upper limb section of the Motor Assessment Scale (MAS) was undertaken. Results: GHS was present in 65 (62%) patients. There was a moderate negative correlation between GHS and muscle strength (r=-0.54,

Paying clinicians to join clinical trials : a review of guidelines and interview study of trialists

Background: The motivations of clinicians to participate in clinical trials have been little studied. This project explored the potential role of payment for participation in publicly funded clinical trials in the UK. The aims were to review relevant guidelines and to collate and analyse views of clinical trialists on the role of payments and other factors that motivated clinicians to join clinical trials. Methods: Review of guidelines governing payments to clinicians for recruitment to trials. Semistructured interviews with a range of NHS clinical trial leaders, analysed using qualititative methods. Results: While UK guidelines had little to say specifically on payments linked to recruitment, all payments have become highly regulated and increasingly transparent. Interview participants believed that expenses arising from research should be covered. Payments in excess of expenses were seen as likely to increase participation but with the risk of reducing quality. Motivations such as interest in the topic, the scope for patients to benefit and intellectual curiosity were considered more important. Barriers to involvement included bureaucracy and lack of time. Discussion: Limited scope exists for paying clinicians over-and-above the cost of their time to be involved in research. Most trialists favour full payment of all expenses related to research. Conclusion: Payment of clinicians beyond expenses is perceived to be a less important motivating factor than researching important, salient questions, and facilitating research by reducing bureaucracy and delay

Professorial roles: a study of the professorial populations within nursing and midwifery, social work and allied health professions

The professorial populations in nursing/midwifery, social work and allied health are relatively new in academia compared to longer established professions such as medicine and dentistry. Less is known about the roles, career pathways, characteristics and career aspirations of the professoriate within these emerging professions. A survey was undertaken from sample populations in each of the three professorial groups in order to obtain qualitative and quantitative data on professorial roles and activities, career pathway information and support mechanisms for professorial positions. This paper discusses the findings of the survey which relate specifically to professorial roles and activities and whether the identified roles reflect the professorial activities proposed by the National Conference of University Professors (NCUP) Other aspects of this survey including career pathways, findings relating to gender and support mechanisms will form the basis of future papers. Result

Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis

BACKGROUND: Since the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required. METHODS: A suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tuberculosis in Nairobi, done pretreatment and at 2, 7, 14 and 28 days. Treatment was with isoniazid and streptomycin, supplemented with either thiacetazone (SHT) or rifampicin + pyrazinamide (SHRZ). RESULTS: During days 0–2, a large kill due to isoniazid occurred, unrelated to treatment or HIV status; thereafter it decreased exponentially. SHRZ appeared to have greater sterilising activity than SHT during days 2–7 (p = 0.044), due to rifampicin, and during days 14–28, probably due mainly to pyrazinamide. The greatest discrimination between SHRZ and SHT treatments was found between regression estimates of kill over days 2–28 (p = 0.0005) in patients who remained positive up to 28 days with homogeneous kill rates. No associations were found between regression estimates and the age, sex, and extent of disease or cavitation. An increased kill in HIV seropositive patients, unrelated to the treatment effect, was evident during days 2–28 (p = 0.007), mainly during days 2–7. CONCLUSIONS: Surrogate marker studies should either be in small groups treated with monotherapy during days 2 to about 7 or as add-ons or replacements in isoniazid-containing standard regimens from days 2 to 28 in large groups

Quitting patient care and career break intentions among general practitioners in South West England: findings of a census survey of general practitioners

Objective: Given recent concerns regarding general practitioner (GP) workforce capacity, we aimed to describe GPs’ career intentions, especially those which might impact on GP workforce availability over the next 5 years. Design: Census survey, conducted between April and June 2016 using postal and online responses , of all GPs on the National Health Service performers list and eligible to practise in primary care. Two reminders were used as necessary. Setting: South West England (population 3.5  million), a region with low overall socioeconomic deprivation. Participants: Eligible GPs were 2248 out of 3370 (67 % response rate). Main outcome measures: Reported likelihood of permanently leaving or reducing hours spent in direct patient care or of taking a career break within the next 5 years and present morale weighted for non-response. Results: Responders included 217 7 GPs engaged in patient care. Of these, 863 (37% weighted, 95%  CI 35 % to 39 %) reported a high likelihood of quitting direct patient care within the next 5 years. Overall, 1535 (70% weighted, 95%  CI 68 % to 72 %) respondents reported a career intention that would negatively impact GP workforce capacity over the next 5 years, through permanently leaving or reducing hours spent in direct patient care, or through taking a career break. GP age was an important predictor of career intentions; sharp increases in the proportion of GPs intending to quit patient care were evident from 52 years. Only 305 (14% weighted, 95%  CI 13 % to 16 %) reported high morale, while 1195 ( 54 % weighted, 95%  CI 52 % to 56 %) reported low morale. Low morale was particularly common among GP partners. Current morale strongly predicted GPs’ career intentions; those with very low morale were particularly likely to report intentions to quit patient care or to take a career break. Conclusions: A substantial majority of GPs in South West England report low morale. Many are considering career intentions which, if implemented, would adversely impact GP workforce capacity within a short time period. Study registration: NIHR HS&DR - 14/196/02, UKCRN ID 20700

Concurrent Silicosis and Pulmonary Mycosis at Death

To examine risk for mycosis among persons with silicosis, we examined US mortality data for 1979–2004. Persons with silicosis were more likely to die with pulmonary mycosis than were those without pneumoconiosis or those with more common pneumoconioses. Health professionals should consider enhanced risk for mycosis for silica-exposed patients

What are the required elements needed to create an effective visual art intervention for people with dementia? A qualitative exploration

Background: This paper aims to advance understanding of ‘what works’ in visual art interventions from the perspective of key stakeholders’, including people with dementia, their family members and visual art professionals. Method: Semi-structured interviews were conducted with 22 participants, exploring their perceptions on barriers, facilitators, perceived benefits, experiences of delivering/attending a visual art intervention, and any recommendations for implementation. Results: Five factors were identified within the interviews that indicated important considerations for intervention structure and implementation, including: benefits of group work, a skilled facilitator, participant choice, artistic ability, and activity content. Whilst art therapists expressed a clear protection of professional boundaries, the success of all of the visual art interventions was largely attributed to the supportive facilitator who possessed certain core values such as empathy and compassion and had knowledge in both artistic practice and the impact of living with dementia. It was clear the group dynamic was valued, and it was important to provide enjoyable, failure-free activity content with a strong focus on the creative process. Conclusion: These findings offer a direction for evidence-based practice when implementing visual art interventions

Selective Inactivity of Pyrazinamide against Tuberculosis in C3HeB/FeJ Mice Is Best Explained by Neutral pH of Caseum

Pyrazinamide (PZA) is one of only two sterilizing drugs in the first-line antituberculosis regimen. Its activity is strongly pH dependent; the MIC changes by several orders of magnitude over a range of pH values that may be encountered in various in vivo compartments. We recently reported selective inactivity of PZA in a subset of C3HeB/FeJ mice with large caseous lung lesions. In the present study, we evaluated whether such inactivity was explained by poor penetration of PZA into such lesions or selection of drug-resistant mutants. Despite demonstrating similar dose-proportional PZA exposures in plasma, epithelial lining fluid, and lung lesions, no dose response was observed in a subset of C3HeB/FeJ mice with the highest CFU burden. Although PZA-resistant mutants eventually replaced the susceptible bacilli in BALB/c mice and in C3HeB/FeJ mice with low total CFU burdens, they never exceeded 1% of the total population in nonresponding C3HeB/FeJ mice. The selective inactivity of PZA in large caseous lesions of C3HeB/FeJ mice is best explained by the neutral pH of liquefying caseum