A Longitudinal Study of Stargardt Disease: Clinical and Electrophysiologic Assessment, Progression, and Genotype Correlations

Purpose: To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype. Design: Cohort study of 59 patients. Methods: Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3 ms for the 30 Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken. Results: The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients. Conclusions: All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions. © 2013 Elsevier Inc. All rights reserved.

Brunetta’s reform swan song? An assessment of its success in local governments through the analysis of its tools

The work aims at assessing the success of Brunetta’s reform (Legislative Decree n. 150/2009), a far-reaching reform that aimed at improving both organizational and individual performance in Italian public administration through a specific planning and control process (the performance cycle) and most of all through two new tools, Performance Plan and Performance Report. The success of the reform is assessed, with particular emphasis on local governments, analyzing the diffusion and use of these new tools. The study has been conducted using a deductive-inductive methodology. Thus, after a study of managerial reforms in Italy and performance measurement literature, a possible model (PerformEL Model) local governments could follow to draw up Performance Plan and Report as effective tools for performance measurement has been designed (deductive phase). Performance Plans 2011-2013 and Performance Report 2011 downloaded from Italian big sized municipalities’ websites have been analyzed in the light of PerformEL Model, to assess the diffusion of the documents and their coherence with legal requirements and suggestions from literature (inductive phase). Data arising from the empirical analysis have been studied to evaluate the diffusion and the effectiveness of big sized municipalities’ Performance Plans and Reports as performance measurement tools and thus to assess the success of the reform (feedback phase). The study shows a scarce diffusion of the documents; they are mostly drew up because of their compulsoriness or to gain legitimization. The results testify the failure of Brunetta’s reform, at least with regard to local governments.

Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry:A randomised controlled trial

Background: Ivacaftor has shown a clinical benefit in patients with cystic fibrosis who have the G551D-CFTR mutation and reduced lung function. Lung clearance index (LCI) using multiple-breath washout might be an alternative to and more sensitive method than forced expiratory volume in 1 s (FEV₁) to assess treatment response in the growing number of children and young adults with cystic fibrosis who have normal spirometry. The aim of the study was to assess the treatment effects of ivacaftor on LCI in patients with cystic fibrosis, a G551D-CFTR mutation, and an FEV₁ >90% predicted. Methods: This phase 2, multicentre, placebo-controlled, double-blind 2×2 crossover study of ivacaftor treatment was conducted in patients with cystic fibrosis, at least one G551D-CFTR allele, and an FEV₁ >90% predicted. Patients also had to have an LCI higher than 7·4 at screening, age of 6 years or older, and a weight higher than or equal to 15 kg. Eligible patients were randomly allocated to receive one of two treatment sequences (placebo first followed by ivacaftor 150 mg twice daily [sequence 1] or ivacaftor 150 mg twice daily first followed by placebo [sequence 2]) of 28 days' treatment in each period, with a 28-day washout between the two treatment periods. Randomisation (ratio 1:1) was done with block sizes of 4, and all site personnel including the investigator, the study monitor, and the Vertex study team were masked to treatment assignment. The primary outcome measure was change from baseline in LCI. The study is registered at ClinicalTrials.gov, NCT01262352. Findings: Between February and November, 2011, 21 patients were enrolled, of which 11 were assigned to the sequence 1 group, and 10 to the sequence 2 group. 20 of these patients received treatment and 17 completed the trial (eight in sequence 1 group and 9 in sequence 2 group). Treatment with ivacaftor led to significant improvements compared with placebo in LCI (difference between groups in the average of mean changes from baseline at days 15 and 29 was -2·16 [95% CI -2·88 to -1·44]; p<0·0001). Adverse events experienced by study participants were similar between treatment groups; at least one adverse event was reported by 15 (79%) of 19 patients who received placebo and 13 (72%) of 18 patients who received ivacaftor. No deaths occurred during study period. Interpretation: In patients with cystic fibrosis aged 6 years or older who have at least one G551D-CFTR allele, ivacaftor led to improvements in LCI. LCI might be a more sensitive alternative to FEV₁ in detecting response to intervention in these patients with mild lung disease. Funding: Vertex Pharmaceuticals Incorporated. © 2013 Elsevier Ltd.

Enhanced clinical pharmacy service targeting tools: risk-predictive algorithms

Rationale, aims and objectives: This study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes. 

Methods: Predictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut-off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database. 

Results: Numbers of previous emergency admissions and admission medicines together with age-adjusted co-morbidity and diuretic receipt formed a 12-month post-discharge and/or readmission risk algorithm. Age-adjusted co-morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk-adjusted mortality index (RAMI). 

Conclusions: Algorithms created were valid in predicting risk of in-hospital and post-discharge mortality and risk of hospital readmission 3, 6 and 12 months post-discharge. The provision of ward-based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized.

Situation Background Assessment Recommendation (SBAR): Undergraduate Perspectives

Situation Background Assessment and Recommendation (SBAR): Undergraduate Perspectives C Morgan, L Adams, J Murray, R Dunlop, IK Walsh. Ian K Walsh, Centre for Medical Education, Queen’s University Belfast, Mulhouse Building, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6DP Background and Purpose: Structured communication tools are used to improve team communication quality.1,2 The Situation Background Assessment and Recommendation (SBAR) tool is widely adopted within patient safety.3 SBAR effectiveness is reportedly equivocal, suggesting use is not sustained beyond initial training.4-6 Understanding perspectives of those using SBAR may further improve clinical communication. We investigated senior medical undergraduate perspectives on SBAR, particularly when communicating with senior colleagues. Methodology: Mixed methods data collection was used. A previously piloted questionnaire with 12 five point Lickert scale questions and 3 open questions was given to all final year medical students. A subgroup also participated in 10 focus groups, deploying strictly structured audio-recorded questions. Selection was by convenience sampling, data gathered by open text questions and comments transcribed verbatim. In-vivo coding (iterative, towards data saturation) preceded thematic analysis. Results: 233 of 255 students (91%) completed the survey. 1. There were clearly contradictory viewpoints on SBAR usage. A recurrent theme was a desire for formal feedback and a relative lack of practice/experience with SBAR. 2. Students reported SBAR as having variable interpretation between individuals; limiting use as a shared mental model. 3. Brief training sessions are insufficient to embed the tool. 4. Most students reported SBAR helping effective communication, especially by providing structure in stressful situations. 5. Only 18.5% of students felt an alternative resource might be needed. Sub analysis of the themes highlighted: A. Lack of clarity regarding what information to include and information placement within the acronym, B. Senior colleague negative response to SBAR C. Lack of conciseness with the tool. Discussion and Conclusions: Despite a wide range of contradictory interpretation of SBAR utility, most students wish to retain the resource. More practice opportunities/feedback may enhance user confidence and understanding. References: (1) Leonard M, Graham S, Bonacum D. The human factor: the critical importance of effective teamwork and communication in providing safe care. Quality & Safety in Health Care 2004 Oct;13(Suppl 1):85-90. (2) d'Agincourt-Canning LG, Kissoon N, Singal M, Pitfield AF. Culture, communication and safety: lessons from the airline industry. Indian J Pediatr 2011 Jun;78(6):703-708. (3) Dunsford J. Structured communication: improving patient safety with SBAR. Nurs Womens Health 2009 Oct;13(5):384-390. (4) Compton J, Copeland K, Flanders S, Cassity C, Spetman M, Xiao Y, et al. Implementing SBAR across a large multihospital health system. Jt Comm J Qual Patient Saf 2012 Jun;38(6):261-268. (5) Ludikhuize J, de Jonge E, Goossens A. Measuring adherence among nurses one year after training in applying the Modified Early Warning Score and Situation-Background-Assessment-Recommendation instruments. Resuscitation 2011 Nov;82(11):1428-1433. (6) Cunningham NJ, Weiland TJ, van Dijk J, Paddle P, Shilkofski N, Cunningham NY. Telephone referrals by junior doctors: a randomised controlled trial assessing the impact of SBAR in a simulated setting. Postgrad Med J 2012 Nov;88(1045):619-626.