Palmar fasciitis and polyarthritis syndrome associated with transitional cell carcinoma of the bladder.

Palmar fasciitis and polyarthritis syndrome is a rare, disabling, paraneoplastic condition of unknown pathogenesis. There is no known effective treatment, although the condition may be halted by control of the cancer. Previously reported cases have mostly been in patients with advanced ovarian malignancies. We present the case of a 69-year-old woman with this condition in association with bladder carcinoma, together with a review of the literature and discussion of possible therapeutic options.

Optimising frontline learning and engagement between consultant-led neonatal teams in the West Midlands: a survey on the utility of an augmented simulation training technique.

BACKGROUND: In England, neonatal care is delivered in operational delivery networks, comprising a combination of the Neonatal Intensive Care (NICU), Local-Neonatal (LNU) or Special-Care Units (SCU), based on their ability to care for babies with different degrees of illness or prematurity. With the development of network care pathways, the most premature and sickest are mostly triaged for delivery in services linked to NICU. This has created anxiety for teams in LNU and SCU. Less exposure to sicker babies has resulted in limited opportunities to maintain expertise for when these babies unexpectedly deliver at their centre and thereafter require transfer for care, to NICU. Simultaneously, LNU and SCU teams develop skills in the care of the less ill and premature baby which would also be of benefit to NICU teams. A need for mutual learning through inter-unit multidirectional collaborative learning and engagement (hereafter also called neonatal networking) between teams of different designations emerged. Here, neonatal networking is defined as collaboration, shared clinical learning and developing an understanding of local systems strengths and challenges between units of different and similar designations. We describe the responses to the development of a clinical and systems focussed platform for this engagement between different teams within our neonatal ODN. METHOD: An interactive 1-day programme was developed in the West Midlands, focussing on a non-hierarchical, equal partnership between neonatal teams from different unit designations. It utilised simulation around clinical scenarios, with a slant towards consultant engagement. Four groups rotating through four clinical simulation scenarios were developed. Each group participated in a clinical simulation scenario, led by a consultant and supported by nurses and doctors in training together with facilitators, with a further ~two consultants, as observers within the group. All were considered learners. Consultant candidates took turns to be participants and observers in the simulation scenarios so that at the end of the day all had led a scenario. Each simulation-clinical debrief session was lengthened by a further ~ 20 min, during which freestyle discussion with all learners occurred. This was to promote further bonding, through multidirectional sharing, and with a systems focus on understanding the strengths and challenges of practices in different units. A consultant focus was adopted to promote a long-term engagement between units around shared care. There were four time points for this neonatal networking during the course of the day. Qualitative assessment and a Likert scale were used to assess this initiative over 4 years. RESULTS: One hundred fifty-five individuals involved in frontline neonatal care participated. Seventy-seven were consultants, supported by neonatal trainees, staff grade doctors, clinical fellows, advanced neonatal nurse practitioners and nurses in training. All were invited to participate in the survey. The survey response rate was 80.6%. Seventy-nine percent felt that this learning strategy was highly relevant; 96% agreed that for consultants this was appropriate adult learning. Ninety-eight percent agreed that consultant training encompassed more than bedside clinical management, including forging communication links between teams. Thematic responses suggested that this was a highly useful method for multi-directional learning around shared care between neonatal units. CONCLUSION: Simulation, enhanced with systems focussed debrief, appeared to be an acceptable method of promoting multidirectional learning within neonatal teams of differing designations within the WMNODN.

Pulmonary vasculitis mimicking chronic thromboembolic disease.

A 29-year-old female patient presented with chest pain, breathlessness and syncope on the background of constitutional symptoms, oral ulceration and a rash. Multiple investigations were performed, including a CT pulmonary angiogram (CTPA) that was initially felt to show imaging features consistent with a diagnosis of chronic thromboembolic disease (CTED). The patient was referred to a tertiary pulmonary hypertension centre and the possibility of pulmonary vasculitis was raised. Subsequent positron emission tomography (PET)-CT revealed imaging features supporting this diagnosis. The patient was treated with intravenous cyclophosphamide infusions, following which her symptoms improved. A repeat PET-CT 6 months after treatment showed resolution in pulmonary artery and mediastinal uptake, but persistence of pulmonary artery occlusions on a repeat CTPA. A final diagnosis of pulmonary vasculitis secondary to Behçet's disease was made. This case report aims to raise awareness of the imaging features of CTED and its mimics.

Using actigraphy to measure sleep patterns in rheumatoid arthritis: a pilot study in patients taking night-time prednisone.

OBJECTIVE: Poor sleep quality is a commonly reported but under-investigated consequence of rheumatoid arthritis (RA). Actigraphy is a non-invasive way of measuring sleep, estimated from the frequency and intensity of physical movement at the wrist. We used actigraphy to measure sleep parameters compared with sleep questionnaire data, and assessed the practicality of actigraph use in patients with RA. METHODS: In a pilot study of actigraphy conducted within an investigation of night-time prednisone treatment and circadian interleukin-6 concentrations in ten patients with active RA, we compared actigraphy with the St Mary's Hospital Sleep Questionnaire and assessed whether night-time administration of prednisone resulted in increased sleep disturbance. RESULTS: The actigraph watch was well tolerated by our patients, producing adequate data for analysis for 128 out of 133 test days (96.2%). The results indicated reasonable concordance between actigraph and sleep questionnaire data in the present sample. Patient satisfaction with sleep (question 11) strongly correlated with sleep efficiency measured by the actigraph (r = 0.71, p = 0.22) and showed a trend for inverse correlation with the fragmentation index (r = -0.60, p = 0.067). Quality of sleep (question 9) correlated non-significantly with the fragmentation index (r = -0.59, p = 0.072). We were unable to identify any significant correlations between clinical measures of disease and sleep parameters in this sample. There were no apparent detrimental consequences of the night-time dose of prednisone on the measures of sleep quality and quantity. CONCLUSION: In spite of the physical disability imposed by RA, the actigraph was well tolerated and gave a useful measure of sleep in patients with active disease. It has the potential for use in larger controlled trials.

Pharmacokinetics of modified-release prednisone tablets in healthy subjects and patients with rheumatoid arthritis.

In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain. Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients. Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night. Single-center crossover studies were conducted, each in ≤24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability. There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C(max) 97%, AUC(0-∞) 101%, 90% confidence intervals within the requisite range for bioequivalence). Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions. Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22:00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.

Efficacy, safety and mechanism of action of modified-release prednisone in rheumatoid arthritis.

Glucocorticoids (GCs) provide a powerful and widely used anti-inflammatory and disease-modifying therapy for rheumatoid arthritis (RA). However, concerns about adverse effects are driving efforts to find 'safer' GC or GC analogues. One novel approach has been to change the timing of GC delivery, targeting the early hours of the morning to suppress the observed circadian peak in interleukin-6 (IL-6). The CAPRA-1 study has shown that this produces a clinically useful beneficial improvement in morning stiffness and mechanistic studies have shown that this correlates with a strong suppression of the IL-6 early morning peak. With no obvious additional adverse reactions, this improvement in the therapeutic ratio offers additional treatment options in RA, and perhaps in other inflammatory diseases that show circadian variation in symptoms.

Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis.

The morning stiffness and pain of rheumatoid arthritis (RA) is accompanied by a rise in serum interleukin-6 (IL-6) from 2 am to 7 am. Using a formulation that releases prednisone at 2 am (after ingestion at 10 pm), we studied the circadian dynamics of serum IL-6, other cytokines, and cortisol in 9 patients before and after 2 weeks, therapy. Significant improvements occurred in morning stiffness, pain, disease activity, and the acute-phase response. Only IL-6 showed measurable cytokine circadian variation, its high pretreatment peak was abolished, and changes in IL-6 correlated with the changes in morning stiffness. Following treatment, afternoon and evening serum cortisol was reduced, but in the early morning cortisol peak concentration increased. Thus the severity of morning symptoms is related to nocturnal serum IL-6 concentration. The specific timing of the medication, linked to the interaction between IL-6 and the hypothalamic-pituitary-adrenal (HPA) axis, may correct a postulated deficiency in HPA control in RA.