Long-term safety study of colistimethate sodium (Colobreathe®): Findings from the UK Cystic Fibrosis Registry.

BACKGROUND: As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics. METHODS: A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations. RESULTS: Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively). CONCLUSIONS: There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety.

Trial-based cost-utility comparison of percutaneous myocardial laser revascularisation and continued medical therapy for treatment of refractory angina pectoris.

This study examined from a health service perspective whether percutaneous myocardial laser revascularisation (PMR) plus standard medical management is cost-effective when compared with standard medical management alone in the treatment of refractory angina. This involved a cost-utility analysis using patient-specific data from a single-centre, randomised, controlled trial carried out in the United Kingdom. Of 73 patients diagnosed as having refractory angina and not suitable for conventional forms of revascularisation, 36 were randomised to PMR plus medical management and 37 to medical management alone. We collected costs to the health service of PMR and all secondary sector health care contacts and cardiac-related medication in the 12 months following randomisation. Patient utility, measured using the EuroQol EQ-5D questionnaire, was combined with 12-month survival data to generate quality-adjusted life years (QALYs). The mean 12-month cost per patient for PMR was 8,307 pounds, and that for medical management was 1,888 pounds, giving a cost difference of 6,410 pounds. The mean QALY difference favoured PMR at 0.126, giving an incremental cost per QALY of 50,873 pounds. The cost-effectiveness acceptability curve indicates that the probability of PMR being cost-effective over the first 12 months is quite low. Whilst a longer period of follow-up might indicate continued benefit from PMR, which would make the intervention economically more attractive, PMR could not be considered cost-effective based on 1-year follow-up data.

Percutaneous myocardial laser revascularization in patients with refractory angina pectoris.

This study aimed to determine the safety and efficacy of percutaneous myocardial laser revascularization (PMLR). Seventy-three patients with stable angina pectoris (class III or IV) who were unsuitable for conventional revascularization and had evidence of reversible ischemia by thallium-201 scintigraphy, ejection fraction of > or =25%, and myocardial wall thickness > or =8 mm were randomized to optimal medical therapy alone (n = 37) or PMLR with optimal medical therapy (n = 36). Patients were followed up at 3, 6, and 12 months. The primary end point was exercise time. Secondary end points included angina scores, left ventricular ejection fraction, quality of life, changes in medical therapy, and hospitalizations. All 36 patients randomized to PMLR underwent the procedure successfully with no periprocedure deaths. One patient developed sustained ventricular tachycardia that required electrical cardioversion, and 1 patient developed cardiac tamponade that required surgical drainage. At 12 months, exercise times improved by 109 seconds in the PMLR group but decreased by 62 seconds in the control group (p <0.01). Angina scores improved by 2 classes in 36% of PMLR-treated patients at 12 months compared with 0% of the control patients (p <0.01). We conclude that PMLR is a relatively safe procedure that provides patients with symptomatic angina relief and improvement in exercise capacity and quality of life.

Evaluation of the clinical effectiveness of the Ventricular Assist Device Program in the United Kingdom (EVAD UK).

BACKGROUND: The UK Government funds ventricular assist device (VAD) implantation as bridge to transplantation (BTT) at three centers. Results from this program have not been published. METHODS: All 70 VAD implants for BTT, 71 inotrope-dependent and 179 non-VAD transplant candidates, accepted for transplantation between April 2002 and December 2004, were prospectively monitored for survival to transplantation, survival overall and quality of life. RESULTS: Of the 70 VAD patients, 31 (44%) survived to heart transplantation, 4 (6%) were bridged to recovery and 5 remained on support at the end of the study. Thirty patients (43%) died while on support. Overall survival from VAD implant was 52% at 1 year. Ten percent of non-VAD inotrope-dependent patients and 9% of routine transplant candidates died while on the waiting list. For transplant recipients, 12-month post-operative survival was 84%, 85% and 84%, respectively, for VAD, inotrope-dependent and routine transplant candidates. VAD and non-VAD patients had similar post-transplant adverse event rates. CONCLUSIONS: There was a role for VAD bridge to transplant for selected patients in the UK, despite the availability of an effective urgent transplant list. VAD patients who underwent transplantation had survival rates similar to other transplant candidates.

Cost-effectiveness of ventricular assist device use in the United Kingdom: results from the evaluation of ventricular assist device programme in the UK (EVAD-UK).

BACKGROUND: The UK Department of Health funds ventricular assist device (VAD) implantation as a bridge to transplantation (BTT) at three centers. The cost-effectiveness of this program has not been established. METHODS: All 70 VAD implants for BTT and a consecutive cohort of 71 inotrope-dependent transplant candidates, between April 2002 and December 2004, were prospectively monitored for survival, transplantation, quality of life and resource use. Costs and quality-adjusted life-years were estimated for these groups, and for a hypothetical scenario in which VAD patients would die within 30 days in the absence of the program. RESULTS: Mean quality-adjusted life-years for a VAD patient was 3.27 at a lifetime cost of 173,841 pounds (316,078 US dollars). The majority of the cost was attributable to the VAD implant (63,830 pounds, 116,056 US dollars) and the initial hospital stay in the ITU and ward (14,500 pounds, 26,364 US dollars). Inotrope-dependent transplant candidates had mean quality-adjusted life-years of 4.99 at a lifetime cost of 130,905 pounds (238,011 US dollars). The worst clinical scenario resulted in a lifetime cost of 14,400 pounds (26,182 US dollars), based on 1 month in the ICU (mean 15 days). These figures were robust to a range of plausible assumptions. CONCLUSIONS: A lifetime model based on current UK practice demonstrates that BTT VAD patients had significant quality-adjusted life-years, but treatment was expensive when compared with the worst clinical scenario. If device technology improves, costs are reduced, or referral practice changes, results should be re-assessed.

An open label, single-centre, randomized trial of spinal cord stimulation vs. percutaneous myocardial laser revascularization in patients with refractory angina pectoris: the SPiRiT trial.

AIMS: Refractory angina pectoris leads to significant morbidity. Treatment options include percutaneous myocardial laser revascularization (PMR) and spinal cord stimulation (SCS). This study was designed to compare these two treatments. METHODS AND RESULTS: Subjects with Canadian Cardiovascular Society (CCS) class 3/4 angina and reversible perfusion defects were randomized to SCS (34) or PMR (34). The primary outcome was to compare exercise treadmill time on a modified Bruce protocol over 12 months. Thirty subjects in both groups completed 12-month follow-up. The mean total exercise time was 6.38 +/- 3.45 min in the SCS group and 7.41+/-3.68 min in the PMR group at baseline and 7.08 +/- 0.67 min in the SCS group and 7.12 +/-0.71 min in the PMR group at 12 months (95% confidence limits for the difference between the groups -1.02 to + 2.2 min, P = 0.466). There were no differences in angina-free exercise capacity, CCS class, and quality of life between treatments. SCS patients had more adverse events in the first 12 months, mainly angina or SCS system related (P = 0.001). CONCLUSION: There was little evidence of a difference in effectiveness between SCS and PMR in patients with refractory angina.

Development and evaluation of the critical care practitioner role.

This article evaluates the establishment and development of the critical care practitioner (CCP) role from 1995 to 1998. The hypothesis was that clinical decisions made by CCPs, for the defined patient group, would result in clinical outcomes and resource usage comparable to those currently experienced. The CCP initiative aimed to provide high quality patient care by expediting the process of making appropriate and timely decisions in the management of routine postoperative cardiac patients. To aid the development and evaluation of the CCP role, data on clinical measures, use of staff time and staff attitudes were collected at baseline, and then at nine months and two years nine months following introduction of the role. The evaluation demonstrated that the introduction of the CCP caused no deterioration in clinical outcomes; there were definite changes in the type of tasks carried out.