Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

The rapid access palliative radiotherapy program: blueprint for initiation of a one-stop multidisciplinary bone metastases clinic.

GOALS OF WORK: Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). MATERIALS AND METHODS: Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked. MAIN RESULTS: Eighty-six patients with painful BM were referred over the 25-week pilot. Median age was 69.9 years; 64% had prostate cancer, and median performance status was 70. Patient-rated pain was on average 6.1/10 at baseline, improving to 2.6/10 by week 4 post-RT. On average, 6.2 symptoms were reported (baseline) compared to 5.2 (week 4). Team members assessed 10-100% of patients and were successful in stabilizing or improving all symptoms in >75% contacted at week 4. One hundred percent of patients surveyed were satisfied with their experience. CONCLUSIONS: Early needs assessment was advantageous in determining the optimal team and methods of assessment for our 'one-stop' BM clinic. This approach was successful in improving pain and other symptoms, and the convenience of seeing multiple providers on 1 day was appreciated by the patients.

Oxygenator exhaust capnography as an index of arterial carbon dioxide tension during cardiopulmonary bypass using a membrane oxygenator.

We have studied the relationship between the partial pressure of carbon dioxide in oxygenator exhaust gas (PECO2) and arterial carbon dioxide tension (PaCO2) during hypothermic cardiopulmonary bypass with non-pulsatile flow and a membrane oxygenator. A total of 172 paired measurements were made in 32 patients, 5 min after starting cardiopulmonary bypass and then at 15-min intervals. Additional measurements were made at 34 degrees C during rewarming. The degree of agreement between paired measurements (PaCO2 and PECO2) at each time was calculated. Mean difference (d) was 0.9 kPa (SD 0.99 kPa). Results were analysed further during stable hypothermia (n = 30, d = 1.88, SD = 0.69), rewarming at 34 degrees C (n = 22, d = 0, SD = 0.84), rewarming at normothermia (n = 48, d = 0.15, SD = 0.69) and with (n = 78, d = 0.62, SD = 0.99) or without (n = 91, d = 1.07, SD = 0.9) carbon dioxide being added to the oxygenator gas. The difference between the two measurements varied in relation to nasopharyngeal temperature if PaCO2 was not corrected for temperature (r2 = 0.343, P = < 0.001). However, if PaCO2 was corrected for temperature, the difference between PaCO2 and PECO2 was not related to temperature, and there was no relationship with either pump blood flow or oxygenator gas flow. We found that measurement of carbon dioxide partial pressure in exhaust gases from a membrane oxygenator during cardiopulmonary bypass was not a useful method for estimating PaCO2.

Adrenaline administered via a nebulizer in adult patients with upper airway obstruction.

Racemic adrenaline administered via a nebulizer has been used successfully in children with upper airway obstruction resulting from croup and postintubation oedema. We report four adult cases of upper airway obstruction of differing aetiologies successfully managed with the administration of adrenaline via a nebulizer (1 mg in 5 ml of normal saline and repeated as necessary). This appears to be safe and effective in selected cases of upper airway obstruction with immediate benefits and few cardiovascular sequelae.