GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

The Tilburg double blind randomised controlled trial comparing inguinal hernia repair according to Lichtenstein and the transinguinal preperitoneal technique

<p>Abstract</p> <p>Background</p> <p>Anterior open treatment of the inguinal hernia with a tension free mesh has reduced the incidence of recurrence and direct postoperative pain. The Lichtenstein procedure rules nowadays as reference technique for hernia treatment. Not recurrences but chronic pain is the main postoperative complication in inguinal hernia repair after Lichtenstein's technique. Preliminary experiences with a soft mesh placed in the preperitoneal space showed good results and less chronic pain.</p> <p>Methods</p> <p>The TULIP is a double-blind randomised controlled trial in which 300 patients will be randomly allocated to anterior inguinal hernia repair according to Lichtenstein or the transinguinal preperitoneal technique with soft mesh. All unilateral primary inguinal hernia patients eligible for operation who meet inclusion criteria will be invited to participate in this trial. The primary endpoint will be direct postoperative- and chronic pain. Secondary endpoints are operation time, postoperative complications, hospital stay, costs, return to daily activities (e.g. work) and recurrence. Both groups will be evaluated.</p> <p>Success rate of hernia repair and complications will be measured as safeguard for quality.</p> <p>To demonstrate that inguinal hernia repair according to the transinguinal preperitoneal (TIPP) technique reduces postoperative pain to <10%, with α = 0,05 and power 80%, a total sample size of 300 patients was calculated.</p> <p>Discussion</p> <p>The TULIP trial is aimed to show a reduction in postoperative chronic pain after anterior hernia repair according to the transinguinal preperitoneal (TIPP) technique, compared to Lichtenstein.</p> <p>In our hypothesis the TIPP technique reduces chronic pain compared to Lichtenstein.</p> <p>Trial registration</p> <p>ISRCTN 93798494</p

The use of preoperative radiotherapy in the management of patients with clinically resectable rectal cancer: a practice guideline

BACKGROUND: This systematic review with meta-analysis was designed to evaluate the literature and to develop recommendations regarding the use of preoperative radiotherapy in the management of patients with resectable rectal cancer. METHODS: The MEDLINE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings of the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were systematically searched for evidence. Relevant reports were reviewed by four members of the Gastrointestinal Cancer Disease Site Group and the references from these reports were searched for additional trials. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Two meta-analyses of preoperative radiotherapy versus surgery alone, nineteen trials that compared preoperative radiotherapy plus surgery to surgery alone, and five trials that compared preoperative radiotherapy to alternative treatments were obtained. Randomized trials demonstrate that preoperative radiotherapy followed by surgery is significantly more effective than surgery alone in preventing local recurrence in patients with resectable rectal cancer and it may also improve survival. A single trial, using surgery with total mesorectal excision, has shown similar benefits in local recurrence. CONCLUSION: For adult patients with clinically resectable rectal cancer we conclude that: • Preoperative radiotherapy is an acceptable alternative to the previous practice of postoperative radiotherapy for patients with stage II and III resectable rectal cancer; • Both preoperative and postoperative radiotherapy decrease local recurrence but neither improves survival as much as postoperative radiotherapy combined with chemotherapy. Therefore, if preoperative radiotherapy is used, chemotherapy should be added postoperatively to at least patients with stage III disease

Guidelines for the management of pregnancy in women with cystic fibrosis

Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF

Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease

Background: Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega-3 PUFA and plant oils in omega-6 PUFA. Evidence suggests increasing PUFA-rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. Objectives: To assess effects of increasing PUFA intake on cardiovascular disease (CVD) and all-cause mortality in adults. Search method: We searched CENTRAL, MEDLINE and Embase to April 2017 and ClinicalTrials.com and World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. Selection criteria: We included randomised controlled trials (RCTs) comparing higher with lower PUFA intakes in adults with or without CVD that assessed effects over ≥12 months. We included full-text, abstracts, trials registry entries and unpublished data. Outcomes were all-cause mortality, CVD mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. Data collection and analysis: Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included studies for further data. Meta-analyses used random-effects analysis, sensitivity analyses included fixed-effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence. Main result: We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Twelve included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA. Increasing PUFA intake probably has little or no effect on all-cause mortality (risk 3.4% vs 3.3% in primary prevention, 11.7% vs 11.5% in secondary prevention, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 24 trials in 19290 participants), but probably reduces risk of CVD events from 5.8% to 4.9% in primary prevention, 23.3% to 20.8% in secondary prevention (RR 0.89, 95% CI 0.79 to 1.01, 20 trials in 17,073 participants), both moderate quality evidence. Increasing PUFA may reduce risk of CHD events from 13.4% to 7.1% primary prevention, 14.3% to 13.7% secondary prevention (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants), CHD death (5.2% to 4.4% primary prevention, 6.8% to 6.1% secondary prevention, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) and may slightly reduce stroke risk (2.1% to 1.5% primary prevention, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, I2 31%, 16 trials, 15,107 participants) all low quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality. Event outcomes were all downgraded for indirectness, as most events occurred in men in westernised countries. Increasing PUFA intake reduces total cholesterol (MD -0.12 mmol/L, 95% CI -0.23 to -0.02, I2 79%, 8072 participants, 26 trials) and probably decreases triglycerides (TG, MD -0.12 mmol/L, 95% CI -0.20 to -0.04, I2 50%, 3905 participants, 20 trials), but has little or no effect on HDL (MD -0.01 mmol/L, 95% CI -0.02 to 0.01, I2 0%, 4674 participants, 18 trials) and LDL (MD -0.01 mmol/L, 95% CI -0.09 to 0.06, I2 44%, 3362 participants, 15 trials). Increasing PUFA probably causes slight weight gain (MD 0.76 kg, 95% CI 0.34 to 1.19, I2 59%, 7100 participants, 12 trials). Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. Authors' conclusions: Increasing PUFA intake probably reduces risk of CVD events, may reduce risk of CHD events and CHD mortality,and may slightly reduce stroke risk, but has little or no effect on all-cause or CVD mortality. The mechanism may be via lipid reduction, but increasing PUFA probably slightly increases weight

The third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke

<p>Abstract</p> <p>Background</p> <p>Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit.</p> <p>Design</p> <p>International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit.</p> <p>Trial procedures</p> <p>Patients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24–48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol).</p> <p>Trial registration</p> <p>ISRCTN25765518</p