Surgery for small asymptomatic abdominal aortic aneurysms.

An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the major abdominal artery. Some AAAs present as emergencies and require surgery; others remain asymptomatic. Treatment of asymptomatic AAAs depends on many factors, but the size of the aneurysm is important, as risk of rupture increases with aneurysm size. Large asymptomatic AAAs (greater than 5.5 cm in diameter) are usually repaired surgically; very small AAAs (less than 4.0 cm diameter) are monitored with ultrasonography. Debate continues over the roles of early repair versus surveillance with repair on subsequent enlargement in people with asymptomatic AAAs of 4.0 cm to 5.5 cm diameter. This is the fourth update of the review first published in 1999. To compare mortality and costs, as well as quality of life and aneurysm rupture as secondary outcomes, following early surgical repair versus routine ultrasound surveillance in people with asymptomatic AAAs between 4.0 cm and 5.5 cm in diameter. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, two other databases, and two trials registers to 10 July 2019. We handsearched conference proceedings and checked reference lists of relevant studies. We included randomised controlled trials where people with asymptomatic AAAs of 4.0 cm to 5.5 cm were randomly allocated to early repair or imaging-based surveillance at least every six months. Outcomes had to include mortality or survival. Three review authors independently extracted data, which were cross-checked by other team members. Outcomes were mortality, costs, quality of life, and aneurysm rupture. For mortality, we estimated risk ratios (RR) (endovascular aneurysm repair only), hazard ratios (HR) (open repair only), and 95% confidence intervals (CI) based on Mantel-Haenszel Chi2 statistics at one and six years (open repair only) following randomisation. We found no new studies for this update. Four trials with 3314 participants fulfilled the inclusion criteria. Two trials compared early open repair with surveillance and two trials compared early endovascular repair (EVAR) with surveillance. We used GRADE to access the certainty of the evidence for mortality and cost, which ranged from high to low. We downgraded the certainty in the evidence from high to moderate and low due to risk of bias concerns and imprecision (some outcomes were only reported by one study). All four trials showed an early survival benefit in the surveillance group (due to 30-day operative mortality with repair) but no evidence of differences in long-term survival. One study compared early open repair with surveillance with an adjusted HR of 0.88 (95% CI 0.75 to 1.02, mean follow-up 10 years; HR 1.21, 95% CI 0.95 to 1.54, mean follow-up 4.9 years). Pooled analysis of participant-level data from the two trials comparing early open repair with surveillance (maximum follow-up seven to eight years) showed no evidence of a difference in survival (propensity score-adjusted HR 0.99, 95% CI 0.83 to 1.18; 2226 participants; high-certainty evidence). This lack of treatment effect did not vary to three years by AAA diameter (P = 0.39), participant age (P = 0.61), or for women (HR 0.84, 95% CI 0.62 to 1.11). Two studies compared EVAR with surveillance and there was no evidence of a survival benefit for early EVAR at 12 months (RR 1.92, 95% CI 0.73 to 5.06; 846 participants; low-certainty evidence). Two trials reported costs. The mean UK health service costs per participant over the first 18 months after randomisation were higher in the open repair surgery than the surveillance group (GBP 4978 in the repair group versus GBP 3914 in the surveillance group; mean difference (MD) GBP 1064, 95% CI 796 to 1332; 1090 participants; moderate-certainty evidence). There was a similar difference after 12 years. The mean USA hospital costs for participants at six months after randomisation were higher in the EVAR group than in the surveillance group (USD 33,471 with repair versus USD 5520 with surveillance; MD USD 27,951, 95% CI 25,156 to 30,746; 614 participants; low-certainty evidence). After four years, there was no evidence of a difference in total medical costs between groups (USD 48,669 with repair versus USD 46,112 with surveillance; MD USD 2557, 95% CI -8043 to 13,156; 614 participants; low-certainty evidence). All studies reported quality of life but used different assessment measurements and results were conflicting. All four studies reported aneurysm rupture. There were very few ruptures reported in the trials of EVAR versus surveillance up to three years. In the trials of open surgery versus surveillance, there were ruptures to at least six years and there were more ruptures in the surveillance group, but most of these ruptures occurred in aneurysms that had exceeded the threshold for surgical repair. There was no evidence of an advantage to early repair for small AAA (4.0 cm to 5.5 cm), regardless of whether open repair or EVAR is used and, at least for open repair, regardless of patient age and AAA diameter. Thus, neither early open nor early EVAR of small AAAs is supported by currently available evidence. Long-term data from the two trials investigating EVAR are not available, so, we can only draw firm conclusions regarding outcomes after the first few years for open repair. Research regarding the risks related to and management of small AAAs in ethnic minorities and women is urgently needed, as data regarding these populations are lacking.

Ulug P ，Powell JT ，Martinez MA ，Ballard DJ ，Filardo G ... -  《Cochrane Database of Systematic Reviews》

Surgery for small asymptomatic abdominal aortic aneurysms.

Filardo G ，Powell JT ，Martinez MA ，Ballard DJ ... -  《Cochrane Database of Systematic Reviews》

Endovascular repair of abdominal aortic aneurysm.

Paravastu SC ，Jayarajasingam R ，Cottam R ，Palfreyman SJ ，Michaels JA ，Thomas SM ... -  《Cochrane Database of Systematic Reviews》

Ultrasound and shockwave therapy for acute fractures in adults.

The morbidity and socioeconomic costs of fractures are considerable. The length of time to healing is an important factor in determining a person's recovery after a fracture. Ultrasound may have a therapeutic role in reducing the time to union after fracture by stimulating osteoblasts and other bone-forming proteins. This is an update of a review previously published in February 2014.   OBJECTIVES: To assess the effects of low-intensity ultrasound (LIPUS), high-intensity focused ultrasound (HIFUS) and extracorporeal shockwave therapies (ECSW) as part of the treatment of acute fractures in adults.  SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase (1980 to March 2022), Orthopaedic Proceedings, trial registers and reference lists of articles. We included randomised controlled trials (RCTs) and quasi-RCTs including participants over 18 years of age with acute fractures (complete or stress fractures) treated with either LIPUS, HIFUS or ECSW versus a control or placebo-control. We used standard methodology expected by Cochrane. We collected data for the following critical outcomes: participant-reported quality of life, quantitative functional improvement, time to return to normal activities, time to fracture union, pain, delayed or non-union of fracture. We also collected data for treatment-related adverse events. We collected data in the short term (up to three months after surgery) and in the medium term (later than three months after surgery).   MAIN RESULTS: We included 21 studies, involving 1543 fractures in 1517 participants; two studies were quasi-RCTs. Twenty studies tested LIPUS and one trial tested ECSW; no studies tested HIFUS. Four studies did not report any of the critical outcomes. All studies had unclear or high risk of bias in at least one domain. The certainty of the evidence was downgraded for imprecision, risk of bias and inconsistency. LIPUS versus control (20 studies, 1459 participants) We found very low-certainty evidence for the effect of LIPUS on Health-related quality of life (HRQoL) measured by SF-36 at up to one year after surgery for lower limb fractures (mean difference (MD) 0.06, 95% confidence interval (CI) -3.85 to 3.97, favours LIPUS; 3 studies, 393 participants). This result was compatible with a clinically important difference of 3 units with both LIPUS or control. There may be little to no difference in time to return to work after people had complete fractures of the upper or lower limbs (MD 1.96 days, 95% CI -2.13 to 6.04, favours control; 2 studies, 370 participants; low-certainty evidence).  There is probably little or no difference in delayed union or non-union up to 12 months after surgery (RR 1.25, 95% CI 0.50 to 3.09, favours control; 7 studies, 746 participants; moderate-certainty evidence). Although data for delayed and non-union included both upper and lower limbs, we noted that there were no incidences of delayed or non-union in upper limb fractures. We did not pool data for time to fracture union (11 studies, 887 participants; very low-certainty evidence) because of substantial statistical heterogeneity which we could not explain. In upper limb fractures, MDs ranged from 0.32 to 40 fewer days to fracture union with LIPUS. In lower limb fractures, MDs ranged from 88 fewer days to 30 more days to fracture union. We also did not pool data for pain experienced at one month after surgery in people with upper limb fractures (2 studies, 148 participants; very low-certainty evidence) because of substantial unexplained statistical heterogeneity. Using a 10-point visual analogue scale, one study reported less pain with LIPUS (MD -1.7, 95% CI -3.03 to -0.37; 47 participants), and the effect was less precise in the other study (MD -0.4, 95% CI -0.61 to 0.53; 101 participants). We found little or no difference in skin irritation (a possible treatment-related adverse event) between groups but judged the certainty of the evidence from this small study to be very low (RR 0.94, 95% CI 0.06 to 14.65; 1 study, 101 participants). No studies reported data for functional recovery. Data for treatment adherence were inconsistently reported across studies, but was generally described to be good. Data for costs were reported for one study, with higher direct costs, as well as combined direct and indirect costs, for LIPUS use. ECSW versus control (1 study, 56 participants) We are uncertain whether ECSW reduces pain at 12 months after surgery in fractures of the lower limb (MD -0.62, 95% CI -0.97 to -0.27, favours ECSW); the difference between pain scores was unlikely to be clinically important, and the certainty of the evidence was very low. We are also uncertain of the effect of ECSW on delayed or non-union at 12 months because the certainty of this evidence is very low (RR 0.56, 95% CI 0.15 to 2.01; 1 study, 57 participants). There were no treatment-related adverse events. This study reported no data for HRQoL, functional recovery, time to return to normal activities, or time to fracture union. In addition, no data were available for adherence or cost. We were uncertain of the effectiveness of ultrasound and shock wave therapy for acute fractures in terms of patient-reported outcome measures (PROMS), for which few studies reported data. It is probable that LIPUS makes little or no difference to delayed union or non-union. Future trials should be double-blind, randomised, placebo-controlled trials recording validated PROMs and following up all trial participants. Whilst time to union is difficult to measure, the proportion of participants achieving clinical and radiographic union at each follow-up point should be ascertained, alongside adherence with the study protocol and cost of treatment in order to better inform clinical practice.

Searle HKC ，Lewis SR ，Coyle C ，Welch M ，Griffin XL ... -  《Cochrane Database of Systematic Reviews》

Oxycodone for cancer-related pain.

Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated Cochrane review previously published in 2017. To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2021. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions. We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference. Two review authors independently sifted the search, extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and pain relief and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall certainty of the evidence using GRADE. For this update, we identified 19 new studies (1836 participants) for inclusion. In total, we included 42 studies which enrolled/randomised 4485 participants, with 3945 of these analysed for efficacy and 4176 for safety. The studies examined a number of different drug comparisons. Controlled-release (CR; typically taken every 12 hours) oxycodone versus immediate-release (IR; taken every 4-6 hours) oxycodone Pooled analysis of three of the four studies comparing CR oxycodone to IR oxycodone suggest that there is little to no difference between CR and IR oxycodone in pain intensity (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.1 to 0.34; n = 319; very low-certainty evidence). The evidence is very uncertain about the effect on adverse events, including constipation (RR 0.71, 95% CI 0.45 to 1.13), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), nausea (RR 0.85, 95% CI 0.56 to 1.28), and vomiting (RR 0.66, 95% CI 0.38 to 1.15) (very low-certainty evidence). There were no data available for quality of life or participant preference, however, three studies suggested that treatment acceptability may be similar between groups (low-certainty evidence). CR oxycodone versus CR morphine The majority of the 24 studies comparing CR oxycodone to CR morphine reported either pain intensity (continuous variable), pain relief (dichotomous variable), or both. Pooled analysis indicated that pain intensity may be lower (better) after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; n = 882 in 7 studies; low-certainty evidence). This SMD is equivalent to a difference of 0.27 points on the Brief Pain Inventory scale (0-10 numerical rating scale), which is not clinically significant. Pooled analyses also suggested that there may be little to no difference in the proportion of participants achieving complete or significant pain relief (RR 1.02, 95% CI 0.95 to 1.10; n = 1249 in 13 studies; low-certainty evidence). The RR for constipation (RR 0.75, 95% CI 0.66 to 0.86) may be lower after treatment with CR oxycodone than after CR morphine. Pooled analyses showed that, for most of the adverse events, the CIs were wide, including no effect as well as potential benefit and harm: drowsiness/somnolence (RR 0.88, 95% CI 0.74 to 1.05), nausea (RR 0.93, 95% CI 0.77 to 1.12), and vomiting (RR 0.81, 95% CI 0.63 to 1.04) (low or very low-certainty evidence). No data were available for quality of life. The evidence is very uncertain about the treatment effects on treatment acceptability and participant preference. Other comparisons The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability. The certainty of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes. The conclusions have not changed since the previous version of this review (in 2017). We found low-certainty evidence that there may be little to no difference in pain intensity, pain relief and adverse events between oxycodone and other strong opioids including morphine, commonly considered the gold standard strong opioid. Although we identified a benefit for pain relief in favour of CR morphine over CR oxycodone, this was not clinically significant and did not persist following sensitivity analysis and so we do not consider this important. However, we found that constipation and hallucinations occurred less often with CR oxycodone than with CR morphine; but the certainty of this evidence was either very low or the finding did not persist following sensitivity analysis, so these findings should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that, while the reliability of the evidence base is low, given the absence of important differences within this analysis, it seems unlikely that larger head-to-head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.

Schmidt-Hansen M ，Bennett MI ，Arnold S ，Bromham N ，Hilgart JS ，Page AJ ，Chi Y ... -  《Cochrane Database of Systematic Reviews》