Temocillin in the treatment of Burkholderia cepacia infection in cystic fibrosis

AbstractBackgroundInfections due to Burkholderia cepacia complex (Bcc) strains increase morbidity and mortality in cystic fibrosis (CF). Some transplant centres reject Bcc infected patients. We reviewed the results in patients treated with i.v temocillin.MethodsTwenty-three patients who received 38 courses of temocillin (1988–1998) were identified from the CF database at Royal Brompton Hospital. In three patients' data were inadequate; therefore analysis was done in 20. Outcome was measured as improvement, deterioration or no change (compared to admission) in the following categories: clinical (temperature, dyspnoea, sputum volume, chest pain), physiological (FEV1, FVC, oxygen saturation) and inflammatory markers (WBC, ESR, CRP). Patients who improved in two categories were classified as having improved. Antibiotic sensitivities and outcome were recorded.ResultsIn 18 of 32 courses (56.25%) improvement occurred. The organism (Bcc) in eight patients' sputum became resistant (three died). The antibiotics was changed in five patients with Bcc strains sensitive to temocillin because of no improvement and one patient due to allergy (rash). The average time to the next i.v antibiotic was 41 days. Eight patients died (in three the Bcc strain was resistant to temocillin). Fourteen patients with Bcc were transplanted and eight patients survived. Another patient who developed Bcc infection post-operatively, failing to respond to temocillin.ConclusionsThese results suggest the potential benefit of i.v temocillin in CF patients with Bcc for exacerbations and at the time of transplantation

Evaluation of methods for one-dimensional spatial analysis of two-dimensional patterns in mouse chimaeras

The relative extent of cell mixing in tissues of mouse chimaeras or mosaics can be studied by comparing the distributions of the two cell populations in the tissues. However, the mean patch size is misleading because it is affected by both the extent of cell mixing and the relative contributions of the two cell populations. Previous work suggested that effects attributable to differences in tissue composition among chimaeras can be factored out either by correcting the mean patch size or by using the median patch size for the minority cell population and restricting the analysis to grossly unbalanced chimaeras. In the present study, computer simulations of two-dimensional mosaic arrays of black and white squares (representing cells) were used to simulate chimaeric tissues. Random arrays simulated tissues with extensive cell mixing, arrays of cell clumps (representing coherent clones) simulated less mixed tissues, and striped arrays simulated tissues with elongated but fragmented descendent clones. The computer simulations predicted that (i) the median patch length (minority cell population) and the corrected mean patch length would both distinguish between random and clumped patterns and (ii) differences in the variation of the composition of two perpendicular series of one-dimensional transects would distinguished between stripes and randomly orientated patches. Both predictions were confirmed by analysis of histological sections of the retinal pigment epithelium from fetal and adult mouse chimaeras. This study demonstrates that two types of non-random two-dimensional variegated patterns (clumps and stripes) can be identified in chimaeras without two-dimensional reconstruction of serial sections

A woman with cystic fibrosis, severe hypoxaemia, an atrial thrombus and a patent foramen ovale: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cystic fibrosis is usually associated with chronic pulmonary sepsis and frequent infective exacerbations. We report a very unusual cause of severe hypoxaemia in a woman with cystic fibrosis caused by thrombus formation in the right atrium.</p> <p>Case presentation</p> <p>A 21-year-old Caucasian woman with cystic fibrosis and a totally implantable venous access device presented with severe hypoxaemia. This was initially treated with antibiotics but her oxygen levels did not improve significantly. Subsequently, a transient ischaemic attack occurred. Further investigations, including a contrast echocardiogram and a cardiac magnetic resonance scan, revealed the presence of a large right atrial thrombus and right-to-left intracardiac shunt through a patent foramen ovale.</p> <p>Conclusion</p> <p>This case highlights the need to consider a right-to-left shunt in chronic respiratory diseases when hypoxaemia is out of proportion to the degree of lung function impairment. Totally implantable venous access devices should always be considered as a source of thrombus formation.</p

Community pharmacists in Englands' opinions on skill-mix and delegation

Objectives Following the 2005 contractual framework amendment, the expanding role of community pharmacy team members required a shift in entrenched views on roles and duties. This study aimed to report on community pharmacists’ opinions on skill mix and explore how they can be addressed so that skill mix may be optimised. Methods An invitation to complete an online questionnaire was distributed via email, marked for the attention of the lead pharmacist. Following a low response, a paper‐based questionnaire was sent to all community pharmacies in England (n = 11,816). Questions elicited data about the respondent, the pharmacy (including staffing profile) and opinions on skill mix. Key findings A total of 1154 returns were received, representing a 10% response rate. Of these, most were pharmacy chains (76%; n = 877), with 5–9 staff (54%; n = 600); commonly open 40–49 hours (42%; n = 487), dispensing <6000 prescriptions per week (41%, n = 533). From 26 statements on skill mix, three factors were identified by principal‐components factor analysis: ‘working well’, ‘feeling the pressure’ and ‘open to development’. Characteristics associated with ‘working well’: pharmacy owners, single businesses, with pharmacy technician(s), dispensing fewer prescriptions and open shorter hours. Characteristics associated with ‘feeling the pressure’: pharmacy chains, open longer hours, large numbers of prescriptions and relief pharmacists. Characteristics associated with ‘open to development’: recently qualified, second pharmacists, working longer hours, chains and dispensing lower numbers of prescriptions. Conclusions Although limited by a low response, results suggest being in a position to influence (more experienced, business owners) may be associated with more positive opinions. Further training (including about legalities and leadership) could contribute to optimising skill mix in community pharmacies

Burkholderia cepacia complex and limited cutaneous vasculitis in patients with cystic fibrosis : a case series

There is a high association of reactive skin presentations, mainly limited cutaneous vasculitis in patients with cystic fibrosis and Burkholderia cepcia complex chronic infection. This may be due to raised levels of circulating inflammatory mediators.Publisher PDFPeer reviewe

Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis

AbstractBackgroundPulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)≥8 mmol L−1 (airway threshold), and are associated with acquisition of respiratory infection.MethodsTo determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry.ResultsAG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5–3 mmol L−1-vs.-0.5–1 mmol L−1, p<0.0001) when BG was ≥8 mmol L−1-vs.-<8 mmol L−1. Daily time with BG≥8 mmol L−1 was CFRD (49±25%), CF-NGT (6±5%), healthy volunteers (1±3%), p<0.0001. Staphylococcus aureus growth increased at ≥0.5 mmol L−1 (p=0.006) and Pseudomonas aeruginosa growth above 1–4 mmol L−1 glucose (p=0.039).ConclusionsBG≥8 mmol L−1 predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent ∼ 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD

An international/multicentre report on patients with cystic fibrosis (CF) over the age of 40 years

AbstractBackgroundThe lifespan of patients with cystic fibrosis (CF) is increasing significantly. The objective of this international pilot study was to study the characteristics of these long-term survivors.MethodsFour centres with large CF clinics from London (UK), Minneapolis (USA), Toronto (Canada) and Verona (Italy) identified 366 patients who had survived 40years and longer.ResultsAt all centres males survived longer than females. There were more pancreatic sufficient patients in Verona (60%) and Toronto (40%) than in London (16%) and Minneapolis (21%). The percentage of ΔF508 homozygous patients varied between 47% in London and 45% in Minneapolis to only 26% in Toronto and 9% in Verona.Average FEV1 and BMI values of the surviving population appeared to stabilise after 40years of age. FEV1 was on average 12% higher in patients who were pancreatic sufficient (p > 0.0001). There was no difference in survival between the centres. The overall median survival after the age of 40 was 13years. The estimated annual death rate was approximately 3.4% from the age of 40–60years.ConclusionsSignificant numbers of patients are now surviving to 40years or more, and it is hoped that an in-depth study of these patients may identify the factors contributing to longer survival

Does Manual Therapy Provide Additional Benefit To Breathing Retraining In The Management Of Dysfunctional Breathing? A Randomised Controlled Trial

Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB. Methods: Sixty subjects with primary DB were randomised into either breathing retraining (standard treatment; n¼30) or breathing retraining plus MT (intervention; n¼30) group. Both the groups received standardised respiratory physiotherapy, which included: DB education, breathing retraining, home regimen, and audio disc. Intervention group subjects additionally received MT following further assessment. Data from 57 subjects were analysed. Results: At baseline, standard treatment group subjects were statistically younger (41.7 + 13.5 versus 50.8 + 13.0 years; p¼0.001) with higher Nijmegen scores (38.6 + 9.5 versus 31.5 + 6.9; p¼0.001). However, no significant difference was found between the groups for primary outcome Nijmegen score (95% CI ( 1.1, 6.6) p¼0.162), or any secondary outcomes (Hospital Anxiety & Depression Score, spirometry or exercise tolerance). Conclusion: Breathing retraining is currently the mainstay of treatment for patients with DB. The results of this study suggest MT provides no additional benefit in this patient group.Juliana Burgess, Dr Robert Wilson, Royal Brompton & Harefield NHS Foundation Trust, and Dr Andy Jones fo

Governing cities for sustainable energy:The UK case

AbstractThe dependence of cities on intensive consumption of energy from fossil fuels is a major cause of climate disruption, and there is increasing interest in the potential for city governments to facilitate a transition to sustainable energy. Little is known, however, about the extent or structures of current urban energy initiatives. Our paper addresses this gap by mapping UK local authority energy plans and project investments and exploring governance processes in three leading cities. It uses socio-technical and urban studies' perspectives on neo-liberal governing and energy systems to interpret findings. This reveals both the gap between local ambitions and capacity to implement plans, and the potential for translation of neo-liberal governing into contrasting commercial and community urban energy enterprises, prefiguring different energy futures. Overall, however, the neo-liberal framework is associated with small scale and uneven initiatives, with limited contribution to a systemic shift to sustainable cities