Population-based interventions for preventing falls and fall-related injuries in older people.

BACKGROUND: Around one-third of older adults aged 65 years or older who live in the community fall each year. Interventions to prevent falls can be designed to target the whole community, rather than selected individuals. These population-level interventions may be facilitated by different healthcare, social care, and community-level agencies. They aim to tackle the determinants that lead to risk of falling in older people, and include components such as community-wide polices for vitamin D supplementation for older adults, reducing fall hazards in the community or people's homes, or providing public health information or implementation of public health programmes that reduce fall risk (e.g. low-cost or free gym membership for older adults to encourage increased physical activity). OBJECTIVES: To review and synthesise the current evidence on the effects of population-based interventions for preventing falls and fall-related injuries in older people. We defined population-based interventions as community-wide initiatives to change the underlying societal, cultural, or environmental conditions increasing the risk of falling. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trials registers in December 2020, and conducted a top-up search of CENTRAL, MEDLINE, and Embase in January 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster RCTs, trials with stepped-wedge designs, and controlled non-randomised studies evaluating population-level interventions for preventing falls and fall-related injuries in adults ≥ 60 years of age. Population-based interventions target entire communities. We excluded studies only targeting people at high risk of falling or with specific comorbidities, or residents living in institutionalised settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane, and used GRADE to assess the certainty of the evidence. We prioritised seven outcomes: rate of falls, number of fallers, number of people experiencing one or more fall-related injuries, number of people experiencing one or more fall-related fracture, number of people requiring hospital admission for one or more falls, adverse events, and economic analysis of interventions. Other outcomes of interest were: number of people experiencing one or more falls requiring medical attention, health-related quality of life, fall-related mortality, and concerns about falling. MAIN RESULTS: We included nine studies: two cluster RCTs and seven non-randomised trials (of which five were controlled before-and-after studies (CBAs), and two were controlled interrupted time series (CITS)). The numbers of older adults in intervention and control regions ranged from 1200 to 137,000 older residents in seven studies. The other two studies reported only total population size rather than numbers of older adults (67,300 and 172,500 residents). Most studies used hospital record systems to collect outcome data, but three only used questionnaire data in a random sample of residents; one study used both methods of data collection. The studies lasted between 14 months and eight years. We used Prevention of Falls Network Europe (ProFaNE) taxonomy to classify the types of interventions. All studies evaluated multicomponent falls prevention interventions. One study (n = 4542) also included a medication and nutrition intervention. We did not pool data owing to lack of consistency in study designs. Medication or nutrition Older people in the intervention area were offered free-of-charge daily supplements of calcium carbonate and vitamin D3. Although female residents exposed to this falls prevention programme had fewer fall-related hospital admissions (with no evidence of a difference for male residents) compared to a control area, we were unsure of this finding because the certainty of evidence was very low. This cluster RCT included high and unclear risks of bias in several domains, and we could not determine levels of imprecision in the effect estimate reported by study authors. Because this evidence is of very low certainty, we have not included quantitative results here. This study reported none of our other review outcomes. Multicomponent interventions Types of interventions included components of exercise, environment modification (home; community; public spaces), staff training, and knowledge and education. Studies included some or all of these components in their programme design. The effectiveness of multicomponent falls prevention interventions for all reported outcomes is uncertain. The two cluster RCTs included high or unclear risk of bias, and we had no reasons to upgrade the certainty of evidence from the non-randomised trial designs (which started as low-certainty evidence). We also noted possible imprecision in some effect estimates and inconsistent findings between studies. Given the very low-certainty evidence for all outcomes, we have not reported quantitative findings here. One cluster RCT reported lower rates of falls in the intervention area than the control area, with fewer people in the intervention area having one or more falls and fall-related injuries, but with little or no difference in the number of people having one or more fall-related fractures. In another cluster RCT (a multi-arm study), study authors reported no evidence of a difference in the number of female or male residents with falls leading to hospital admission after either a multicomponent intervention ("environmental and health programme") or a combination of this programme and the calcium and vitamin D3 programme (above). One CBA reported no difference in rate of falls between intervention and control group areas, and another CBA reported no difference in rate of falls inside or outside the home. Two CBAs found no evidence of a difference in the number of fallers, and another CBA found no evidence of a difference in fall-related injuries. One CITS found no evidence of a difference in the number of people having one or more fall-related fractures. No studies reported adverse events. AUTHORS' CONCLUSIONS: Given the very low-certainty evidence, we are unsure whether population-based multicomponent or nutrition and medication interventions are effective at reducing falls and fall-related injuries in older adults. Methodologically robust cluster RCTs with sufficiently large communities and numbers of clusters are needed. Establishing a rate of sampling for population-based studies would help in determining the size of communities to include. Interventions should be described in detail to allow investigation of effectiveness of individual components of multicomponent interventions; using the ProFaNE taxonomy for this would improve consistency between studies.

Surgical versus non-surgical interventions for displaced intra-articular calcaneal fractures.

BACKGROUND: Fractures of the calcaneus (heel bone) comprise up to 2% of all fractures. These fractures are mostly caused by a fall from a height, and are common in younger adults. Treatment can be surgical or non-surgical; however, there is clinical uncertainty over optimal management. This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To assess the effects (benefits and harms) of surgical versus conservative treatment of displaced intra-articular calcaneal fractures. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL, MEDLINE, Embase, and clinical trials registers in November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing surgical versus non-surgical management of displaced intra-articular calcaneal fractures in skeletally mature adults (older than 14 years of age). For surgical treatment, we included closed manipulation with percutaneous wire fixation, open reduction with internal fixation (ORIF) with or without bone graft, or primary arthrodesis. For non-surgical treatment, we included ice, elevation and rest, or plaster cast or splint immobilisation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We collected data for the following outcomes: function in the short term (within three months of injury) or long term (more than three months after injury), chronic pain, health-related quality of life (HRQoL) and ability to return to normal activities, as well as complications which may or may not have led to an unplanned return to theatre. MAIN RESULTS: We included 10 RCTs and two quasi-RCTs with 1097 participants. Sample sizes in studies ranged from 29 to 424 participants. Most participants were male (86%), and the mean age in studies ranged from 28 to 52 years. In the surgical groups, participants were mostly managed with ORIF with plates, screws, or wires; one study used only minimally invasive techniques. Participants in the non-surgical groups were managed with a plaster cast, removable splint or a bandage, or with rest, elevation, and sometimes ice. Risk of performance bias was unavoidably high in all studies as it was not possible to blind participants and personnel to treatment; in addition, some studies were at high or unclear risk of other types of bias (including high risk of selection bias for quasi-RCTs, high risk of attrition bias, and unclear risk of selective reporting bias). We downgraded the certainty of all the evidence for serious risk of bias. We also downgraded the certainty of the evidence for imprecision for all outcomes (except for complications requiring return to theatre for subtalar arthrodesis) because the evidence was derived from few participants. We downgraded the evidence for subtalar arthrodesis for inconsistency because the pooled data included high levels of statistical heterogeneity. We found that surgical management may improve function at six to 24 months after injury when measured using the American Orthopaedic Foot and Ankle Society (AOFAS) score (mean difference (MD) 6.58, 95% confidence interval (CI) 1.04 to 12.12; 5 studies, 319 participants; low-certainty evidence). We are not aware of a published minimal clinically important difference (MCID) for the AOFAS score for this type of fracture. Previously published MCIDs for other foot conditions range from 2.0 to 7.9. No studies reported short-term function within three months of injury. Surgical management may reduce the number of people with chronic pain up to 24 months after injury (risk ratio (RR) 0.56, 95% CI 0.37 to 0.84; 4 studies, 175 participants; low-certainty evidence); this equates to 295 per 1000 fewer people with pain after surgical management (95% CI 107 to 422 per 1000). Surgical management may also lead to improved physical HRQoL (MD 6.49, 95% CI 2.49 to 10.48; 2 studies, 192 participants; low-certainty evidence). This outcome was measured using the physical component score of the 36-Item Short Form Health Survey. We used a change in effect of 5% to indicate a clinically important difference for this scoring system and thus judged that the difference in HRQoL between people treated surgically or non-surgically includes both clinically relevant and not relevant changes for those treated surgically. There may be little or no difference in the number of people who returned to work within 24 months (RR 1.26, 95% CI 0.94 to 1.68; 5 studies, 250 participants; low-certainty evidence) or who require secondary surgery for subtalar arthrodesis (RR 0.38, 95% CI 0.09 to 1.53; 3 studies, 657 participants; low-certainty evidence). For other complications requiring return to theatre in people treated surgically, we found low-certainty evidence for amputation (2.4%; 1 study, 42 participants), implant removal (3.4%; 3 studies, 321 participants), deep infection (5.3%; 1 study, 206 participants), and wound debridement (2.7%; 1 study, 73 participants). We found low-certainty evidence that 14% of participants who were treated surgically (7 studies, 847 participants) had superficial site infection. AUTHORS' CONCLUSIONS: Our confidence in the evidence is limited. Although pooled evidence indicated that surgical treatment may lead to improved functional outcome but with an increased risk of unplanned second operations, we judged the evidence to be of low certainty as it was often derived from few participants in studies that were not sufficiently robust in design. We found no evidence of a difference between treatment options in the number of people who needed late reconstruction surgery for subtalar arthritis, although the estimate included the possibility of important harms and benefits. Large, well-conducted studies that attempt to minimise detection bias and that measure functional outcomes using calcaneal-specific measurement tools would increase the confidence in these findings. Given that minimally invasive surgical procedures are already becoming more prevalent in practice, research is urgently needed to determine whether these newer surgical techniques offer better outcomes with regard to function, pain, quality of life, and postoperative complications for intra-articular displaced calcaneal fractures.

Interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews.

BACKGROUND: Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults, blood loss may be compounded by pre-existing anaemia. Allogenic blood transfusions (ABT) may be given before, during, and after surgery to correct chronic anaemia or acute blood loss. However, there is uncertainty about the benefit-risk ratio for ABT. This is a potentially scarce resource, with availability of blood products sometimes uncertain. Other strategies from Patient Blood Management may prevent or minimise blood loss and avoid administration of ABT. OBJECTIVES: To summarise the evidence from Cochrane Reviews and other systematic reviews of randomised or quasi-randomised trials evaluating the effects of pharmacological and non-pharmacological interventions, administered perioperatively, on reducing blood loss, anaemia, and the need for ABT in adults undergoing hip fracture surgery. METHODS: In January 2022, we searched the Cochrane Library, MEDLINE, Embase, and five other databases for systematic reviews of randomised controlled trials (RCTs) of interventions given to prevent or minimise blood loss, treat the effects of anaemia, and reduce the need for ABT, in adults undergoing hip fracture surgery. We searched for pharmacological interventions (fibrinogen, factor VIIa and factor XIII, desmopressin, antifibrinolytics, fibrin and non-fibrin sealants and glue, agents to reverse the effects of anticoagulants, erythropoiesis agents, iron, vitamin B12, and folate replacement therapy) and non-pharmacological interventions (surgical approaches to reduce or manage blood loss, intraoperative cell salvage and autologous blood transfusion, temperature management, and oxygen therapy). We used Cochrane methodology, and assessed the methodological quality of included reviews using AMSTAR 2. We assessed the degree of overlap of RCTs between reviews. Because overlap was very high, we used a hierarchical approach to select reviews from which to report data; we compared the findings of selected reviews with findings from the other reviews. Outcomes were: number of people requiring ABT, volume of transfused blood (measured as units of packed red blood cells (PRC)), postoperative delirium, adverse events, activities of daily living (ADL), health-related quality of life (HRQoL), and mortality. MAIN RESULTS: We found 26 systematic reviews including 36 RCTs (3923 participants), which only evaluated tranexamic acid and iron. We found no reviews of other pharmacological interventions or any non-pharmacological interventions. Tranexamic acid (17 reviews, 29 eligible RCTs) We selected reviews with the most recent search date, and which included data for the most outcomes. The methodological quality of these reviews was low. However, the findings were largely consistent across reviews. One review included 24 RCTs, with participants who had internal fixation or arthroplasty for different types of hip fracture. Tranexamic acid was given intravenously or topically during the perioperative period. In this review, based on a control group risk of 451 people per 1000, 194 fewer people per 1000 probably require ABT after receiving tranexamic acid (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.46 to 0.68; 21 studies, 2148 participants; moderate-certainty evidence). We downgraded the certainty for possible publication bias. Review authors found that there was probably little or no difference in the risks of adverse events, reported as deep vein thrombosis (RR 1.16, 95% CI 0.74 to 1.81; 22 studies), pulmonary embolism (RR 1.01, 95% CI 0.36 to 2.86; 9 studies), myocardial infarction (RR 1.00, 95% CI 0.23 to 4.33; 8 studies), cerebrovascular accident (RR 1.45, 95% CI 0.56 to 3.70; 8 studies), or death (RR 1.01, 95% CI 0.70 to 1.46; 10 studies). We judged evidence from these outcomes to be moderate certainty, downgraded for imprecision. Another review, with a similarly broad inclusion criteria, included 10 studies, and found that tranexamic acid probably reduces the volume of transfused PRC (0.53 fewer units, 95% CI 0.27 to 0.80; 7 studies, 813 participants; moderate-certainty evidence). We downgraded the certainty because of unexplained high levels of statistical heterogeneity. No reviews reported outcomes of postoperative delirium, ADL, or HRQoL. Iron (9 reviews, 7 eligible RCTs) Whilst all reviews included studies in hip fracture populations, most also included other surgical populations. The most current, direct evidence was reported in two RCTs, with 403 participants with hip fracture; iron was given intravenously, starting preoperatively. This review did not include evidence for iron with erythropoietin. The methodological quality of this review was low. In this review, there was low-certainty evidence from two studies (403 participants) that there may be little or no difference according to whether intravenous iron was given in: the number of people who required ABT (RR 0.90, 95% CI 0.73 to 1.11), the volume of transfused blood (MD -0.07 units of PRC, 95% CI -0.31 to 0.17), infection (RR 0.99, 95% CI 0.55 to 1.80), or mortality within 30 days (RR 1.06, 95% CI 0.53 to 2.13). There may be little or no difference in delirium (25 events in the iron group compared to 26 events in control group; 1 study, 303 participants; low-certainty evidence). We are very unsure whether there was any difference in HRQoL, since it was reported without an effect estimate. The findings were largely consistent across reviews. We downgraded the evidence for imprecision, because studies included few participants, and the wide CIs indicated possible benefit and harm. No reviews reported outcomes of cognitive dysfunction, ADL, or HRQoL. AUTHORS' CONCLUSIONS: Tranexamic acid probably reduces the need for ABT in adults undergoing hip fracture surgery, and there is probably little or no difference in adverse events. For iron, there may be little or no difference in overall clinical effects, but this finding is limited by evidence from only a few small studies. Reviews of these treatments did not adequately include patient-reported outcome measures (PROMS), and evidence for their effectiveness remains incomplete. We were unable to effectively explore the impact of timing and route of administration between reviews. A lack of systematic reviews for other types of pharmacological or any non-pharmacological interventions to reduce the need for ABT indicates a need for further evidence syntheses to explore this. Methodologically sound evidence syntheses should include PROMS within four months of surgery.

Interventions for the symptoms and signs resulting from jellyfish stings.

BACKGROUND: Jellyfish envenomation is common in many coastal regions and varies in severity depending upon the species. Stings cause a variety of symptoms and signs including pain, dermatological reactions, and, in some species, Irukandji syndrome (which may include abdominal/back/chest pain, tachycardia, hypertension, cardiac phenomena, and, rarely, death). Many treatments have been suggested for these symptoms, but their effectiveness is unclear. This is an update of a Cochrane Review last published in 2013. OBJECTIVES: To determine the benefits and harms associated with the use of any intervention, in both adults and children, for the treatment of jellyfish stings, as assessed by randomised and quasi-randomised trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and Web of Science up to 27 October 2022. We searched clinical trials registers and the grey literature, and conducted forward-citation searching of relevant articles.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of any intervention given to treat stings from any species of jellyfish stings. Interventions were compared to another active intervention, placebo, or no treatment. If co-interventions were used, we included the study only if the co-intervention was used in each group.  DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  MAIN RESULTS: We included nine studies (six RCTs and three quasi-RCTs) involving a total of 574 participants. We found one ongoing study. Participants were either stung accidentally, or were healthy volunteers exposed to stings in a laboratory setting. Type of jellyfish could not be confirmed in beach settings and was determined by investigators using participant and local information. We categorised interventions into comparison groups: hot versus cold applications; topical applications. A third comparison of parenteral administration included no relevant outcome data: a single study (39 participants) evaluated intravenous magnesium sulfate after stings from jellyfish that cause Irukandji syndrome (Carukia). No studies assessed a fourth comparison group of pressure immobilisation bandages.  We downgraded the certainty of the evidence due to very serious risk of bias, serious and very serious imprecision, and serious inconsistency in some results.  Application of heat versus application of cold Four studies involved accidental stings treated on the beach or in hospital. Jellyfish were described as bluebottles (Physalia; location: Australia), and box jellyfish that do not cause Irukandji syndrome (Hawaiian box jellyfish (Carybdea alata) and major box jellyfish (Chironex fleckeri, location: Australia)). Treatments were applied with hot packs or hot water (showers, baths, buckets, or hoses), or ice packs or cold packs.  The evidence for all outcomes was of very low certainty, thus we are unsure whether heat compared to cold leads to at least a clinically significant reduction in pain within six hours of stings from Physalia (risk ratio (RR) 2.25, 95% confidence interval (CI) 1.42 to 3.56; 2 studies, 142 participants) or Carybdea alata and Chironex fleckeri (RR 1.66, 95% CI 0.56 to 4.94; 2 studies, 71 participants). We are unsure whether there is a difference in adverse events due to treatment (RR 0.50, 95% CI 0.05 to 5.19; 2 studies, 142 participants); these were minor adverse events reported for Physalia stings. We are also unsure whether either treatment leads to a clinically significant reduction in pain in the first hour (Physalia: RR 2.66, 95% CI 1.71 to 4.15; 1 study, 88 participants; Carybdea alata and Chironex fleckeri: RR 1.16, 95% CI 0.71 to 1.89; 1 study, 42 participants) or cessation of pain at the end of treatment (Physalia: RR 1.63, 95% CI 0.81 to 3.27; 1 study, 54 participants; Carybdea alata and Chironex fleckeri: RR 3.54, 95% CI 0.82 to 15.31; 1 study, 29 participants). Evidence for retreatment with the same intervention was only available for Physalia, with similar uncertain findings (RR 0.19, 95% CI 0.01 to 3.90; 1 study, 96 participants), as was the case for retreatment with the alternative hot or cold application after Physalia (RR 1.00, 95% CI 0.55 to 1.82; 1 study, 54 participants) and Chironex fleckeri stings (RR 0.48, 95% CI 0.02 to 11.17; 1 study, 42 participants). Evidence for dermatological signs (itchiness or rash) was available only at 24 hours for Physalia stings (RR 1.02, 95% CI 0.63 to 1.65; 2 studies, 98 participants).  Topical applications One study (62 participants) included accidental stings from Hawaiian box jellyfish (Carybdea alata) treated on the beach with fresh water, seawater, Sting Aid (a commercial product), or Adolph's (papain) meat tenderiser. In another study, healthy volunteers (97 participants) were stung with an Indonesian sea nettle (Chrysaora chinensis from Malaysia) in a laboratory setting and treated with isopropyl alcohol, ammonia, heated water, acetic acid, or sodium bicarbonate. Two other eligible studies (Carybdea alata and Physalia stings) did not measure the outcomes of this review.  The evidence for all outcomes was of very low certainty, thus we could not be certain whether or not topical applications provided at least a clinically significant reduction in pain (1 study, 62 participants with Carybdea alata stings, reported only as cessation of pain). For adverse events due to treatment, one study (Chrysaora chinensis stings) withdrew ammonia as a treatment following a first-degree burn in one participant. No studies evaluated clinically significant reduction in pain, retreatment with the same or the alternative treatment, or dermatological signs. AUTHORS' CONCLUSIONS: Few studies contributed data to this review, and those that did contribute varied in types of treatment, settings, and range of jellyfish species. We are unsure of the effectiveness of any of the treatments evaluated in this review given the very low certainty of all the evidence. This updated review includes two new studies (with 139 additional participants). The findings are consistent with the previous review.

Ultrasound and shockwave therapy for acute fractures in adults.

BACKGROUND: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. AUTHORS' CONCLUSIONS: 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.

Effectiveness of the perioperative encounter in promoting regular exercise and physical activity: a systematic review and meta-analysis.

Background: Low levels of physical activity (PA) are associated with poorer health outcomes. The perioperative encounter (extending from initial contact in primary care to beyond discharge from hospital) is potentially a good time to intervene, but data regarding the effectiveness of interventions are scarce. To address this, we systematically reviewed existing literature to evaluate the effectiveness of interventions applied perioperatively to facilitate PA in the medium to long-term (at least six months after the intervention). Methods: In this systematic review and meta-analysis, we searched Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, CINAHL, Embase, PsycInfo, and SPORTDiscus from database inception to October 22nd 2020, with an updated search done on August 4th 2022. We searched clinical trials registers, and conducted forward- and backward-citation searches. We included randomised controlled trials and quasi-randomised trials comparing PA interventions with usual care, or another PA intervention, in adults who were scheduled for, or had recently undergone, surgery. We included trials which reported our primary outcomes: amount of PA or whether participants were engaged in PA at least six months after the intervention. A random effects meta-analysis was used to pool data across studies as risk ratios (RR), or standardised mean differences (SMDs), which we interpreted using Cohen. We used the Cochrane risk of bias tool and used GRADE to assess the certainty of the evidence. This study is registered with PROSPERO, CRD42019139008. Findings: We found 57 trials including 8548 adults and compared 71 interventions facilitating PA. Most interventions were started postoperatively and included multiple components. Compared with usual care, interventions may slightly increase the number of minutes of PA per day or week (SMD 0.17, 95% CI 0.09-0.26; 14 studies, 2172 participants; I2 = 0%), and people's engagement in PA at the study's end (RR 1.19, 95% CI 0.96-1.47; 9 studies, 882 participants; I2 = 25%); this was moderate-certainty evidence. Some studies compared two different types of interventions but it was often not feasible to combine data in analysis. The effect estimates generally indicated little difference between intervention designs and we judged all the evidence for these comparisons to be very low certainty. Thirty-six studies (63%) had low risk of selection bias for sequence generation, 27 studies (47%) had low risk of bias for allocation concealment, and 56 studies (98%) had a high risk of performance bias. For detection bias for PA outcomes, we judged 30 studies (53%) that used subjective measurement tools to have a high risk of detection bias. Interpretation: Interventions delivered in the perioperative setting, aimed at enhancing PA in the medium to long-term, may have overall benefit. However, because of imprecision in some of the findings, we could not rule out the possibility of no change in PA. Funding: National Institute for Health Research Health Services and Delivery Research programme (NIHR127879).

Videolaryngoscopy versus direct laryngoscopy for adults undergoing tracheal intubation: a Cochrane systematic review and meta-analysis update.

BACKGROUND: Tracheal intubation is a commonly performed procedure that can be associated with complications and result in patient harm. Videolaryngoscopy (VL) may decrease this risk as compared with Macintosh direct laryngoscopy (DL). This review evaluates the risk and benefit profile of VL compared with DL in adults. METHODS: We searched MEDLINE, Embase, CENTRAL, and Web of Science on February 27, 2021. We included RCTs comparing VL with DL in patients undergoing tracheal intubation in any setting. We separately compared outcomes according to VL design: Macintosh-style, hyperangulated, and channelled. RESULTS: A total of 222 RCTs (with 26 149 participants) were included. Most studies had unclear risk of bias in at least one domain, and all were at high risk of performance and detection bias. We found that videolaryngoscopes of any design likely reduce rates of failed intubation (Macintosh-style: risk ratio [RR]=0.41; 95% confidence interval [CI], 0.26-0.65; hyperangulated: RR=0.51; 95% CI, 0.34-0.76; channelled: RR=0.43, 95% CI, 0.30-0.61; moderate-certainty evidence) with increased rates of successful intubation on first attempt and better glottic views across patient groups and settings. Hyperangulated designs are likely favourable in terms of reducing the rate of oesophageal intubation, and result in improved rates of successful intubation in individuals presenting with difficult airway features (P=0.03). We also present other patient-oriented outcomes. CONCLUSIONS: In this systematic review and meta-analysis of trials of adults undergoing tracheal intubation, VL was associated with fewer failed attempts and complications such as hypoxaemia, whereas glottic views were improved. SYSTEMATIC REVIEW REGISTRATION: This article is based on a Cochrane Review published in the Cochrane Database of Systematic Reviews (CDSR) 2022, Issue 4, DOI: 10.1002/14651858.CD011136.pub3 (see www.cochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the CDSR should be consulted for the most recent version of the review.

Interventions for treating supracondylar elbow fractures in children.

BACKGROUND: Elbow supracondylar fractures are common, with treatment decisions based on fracture displacement. However, there remains controversy regarding the best treatments for this injury. OBJECTIVES: To assess the effects (benefits and harms) of interventions for treating supracondylar elbow fractures in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase in March 2021. We also searched trial registers and reference lists. We applied no language or publication restrictions. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials comparing different interventions for the treatment of supracondylar elbow fractures in children. We included studies investigating surgical interventions (different fixation techniques and different reduction techniques), surgical versus non-surgical treatment, traction types, methods of non-surgical intervention, and timing and location of treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data and conducted GRADE assessment for five critical outcomes: functional outcomes, treatment failure (requiring re-intervention), nerve injury, major complications (pin site infection in most studies), and cosmetic deformity (cubitus varus).  MAIN RESULTS: We included 52 trials with 3594 children who had supracondylar elbow fractures; most were Gartland 2 and 3 fractures. The mean ages of children ranged from 4.9 to 8.4 years and the majority of participants were boys. Most studies (33) were conducted in countries in South-East Asia. We identified 12 different comparisons of interventions: retrograde lateral wires versus retrograde crossed wires; lateral crossed (Dorgan) wires versus retrograde crossed wires; retrograde lateral wires versus lateral crossed (Dorgan) wires; retrograde crossed wires versus posterior intrafocal wires; retrograde lateral wires in a parallel versus divergent configuration; retrograde crossed wires using a mini-open technique or inserted percutaneously; buried versus non-buried wires; external versus internal fixation; open versus closed reduction; surgical fixation versus non-surgical immobilisation; skeletal versus skin traction; and collar and cuff versus backslab. We report here the findings of four comparisons that represent the most substantial body of evidence for the most clinically relevant comparisons.  All studies in these four comparisons had unclear risks of bias in at least one domain. We downgraded the certainty of all outcomes for serious risks of bias, for imprecision when evidence was derived from a small sample size or had a wide confidence interval (CI) that included the possibility of benefits or harms for both treatments, and when we detected the possibility of publication bias.  Retrograde lateral wires versus retrograde crossed wires (29 studies, 2068 children) There was low-certainty evidence of less nerve injury with retrograde lateral wires (RR 0.65, 95% CI 0.46 to 0.90; 28 studies, 1653 children). In a post hoc subgroup analysis, we noted a greater difference in the number of children with nerve injuries when lateral wires were compared to crossed wires inserted with a  percutaneous medial wire technique (RR 0.41, 95% CI 0.20 to 0.81, favours lateral wires; 10 studies, 552 children), but little difference when an open technique was used (RR 0.91, 95% CI 0.59 to 1.40, favours lateral wires; 11 studies, 656 children). Although we noted a statistically significant difference between these subgroups from the interaction test (P = 0.05), we could not rule out the possibility that other factors could account for this difference. We found little or no difference between the interventions in major complications, which were described as pin site infections in all studies (RR 1.08, 95% CI 0.65 to 1.79; 19 studies, 1126 children; low-certainty evidence). For functional status (1 study, 35 children), treatment failure requiring re-intervention (1 study, 60 children), and cosmetic deformity (2 studies, 95 children), there was very low-certainty evidence showing no evidence of a difference between interventions. Open reduction versus closed reduction (4 studies, 295 children) Type of reduction method may make little or no difference to nerve injuries (RR 0.30, 95% CI 0.09 to 1.01, favours open reduction; 3 studies, 163 children). However, there may be fewer major complications (pin site infections) when closed reduction is used (RR 4.15, 95% CI 1.07 to 16.20; 4 studies, 253 children). The certainty of the evidence for these outcomes is low. No studies reported functional outcome, treatment failure requiring re-intervention, or cosmetic deformity. The four studies in this comparison used direct visualisation during surgery. One additional study used a joystick technique for reduction, and we did not combine data from this study in analyses. Surgical fixation using wires versus non-surgical immobilisation using a cast (3 studies, 140 children) There was very low-certainty evidence showing little or no difference between interventions for treatment failure requiring re-intervention (1 study, 60 children), nerve injury (3 studies, 140 children), major complications (3 studies, 126 children), and cosmetic deformity (2 studies, 80 children). No studies reported functional outcome. Backslab versus sling (1 study, 50 children) No nerve injuries or major complications were experienced by children in either group; this evidence is of very low certainty. Functional outcome, treatment failure, and cosmetic deformity were not reported.  AUTHORS' CONCLUSIONS: We found insufficient evidence for many treatments of supracondylar fractures. Fixation of displaced supracondylar fractures with retrograde lateral wires compared with crossed wires provided the most substantial body of evidence in this review, and our findings indicate that there may be a lower risk of nerve injury with retrograde lateral wires. In future trials of treatments, we would encourage the adoption of a core outcome set, which includes patient-reported measures. Evaluation of the effectiveness of traction compared with surgical fixation would provide a valuable addition to this clinical field.

Cánulas nasales de alto flujo para la asistencia respiratoria en pacientes adultos de cuidados intensivos / High-flow nasal cannulae for respiratory support in adult intensive care patient

No disponible

Timing of antibiotic administration, wound debridement, and the stages of reconstructive surgery for open long bone fractures of the upper and lower limbs.

BACKGROUND: Open fractures of the major long bones are complex limb-threatening injuries that are predisposed to deep infection. Treatment includes antibiotics and surgery to debride the wound, stabilise the fracture and reconstruct any soft tissue defect to enable infection-free bone repair. There is a need to assess the effect of timing and duration of antibiotic administration and timing and staging of surgical interventions to optimise outcomes. OBJECTIVES: To assess the effects (risks and benefits) of the timing of antibiotic administration, wound debridement and the stages of surgical interventions in managing people with open long bone fractures of the upper and lower limbs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trial registers in February 2021. We also searched conference proceedings and reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that recruited adults with open fractures of the major long bones, comparing: 1) timings of prophylactic antibiotic treatment, 2) duration of prophylactic antibiotic treatment, 3) timing of wound debridement following injury or 4) timing of the stages of reconstructive surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We aimed to collect data for the following outcomes: limb function, health-related quality of life (HRQoL), deep surgical site infection, delayed or non-union, adverse events (in the short- and long-term course of recovery), and resource-related outcomes. MAIN RESULTS: We included three RCTs of 613 randomised participants with 617 open fractures. Studies were conducted in medical and trauma centres in the USA and Kenya. Where reported, there was a higher proportion of men and a mean age of participants between 30 and 34 years old. Fractures were in the upper and lower limbs in one study, and were tibia fractures in two studies; where reported, these were the result of high-energy trauma such as road traffic accidents. No studies compared the timing of antibiotic treatment or wound debridement. Duration of prophylactic antibiotic treatment (1 study, 77 participants available for analysis) One study compared antibiotic treatment for 24 hours with antibiotic treatment for five days. We are very uncertain about the effects of different durations of antibiotic treatment on superficial infections (risk ratio (RR) 1.19, 95% CI 0.49 to 2.87, favours 5 day treatment; 1 study, 77 participants); this was very low-certainty evidence derived from one small study with unclear and high risks of bias, and with an imprecise effect estimate. This study reported no other review outcomes. Reconstructive surgery: timing of the stages of surgery (2 studies, 458 participants available for analysis) Two studies compared the timing of wound closure, which was completed immediately or delayed. In one study, the mean time of delay was 5.9 days; in the other study, the time of delay was not reported. We are very uncertain about the effects of different timings of wound closure on deep infections (RR 0.82, 95% CI 0.37 to 1.80, favours immediate closure; 2 studies, 458 participants), delayed union or non-union (RR 1.13, 95% CI 0.83 to 1.55, favours delayed closure; 1 study, 387 participants), or superficial infections (RR 6.45, 95% CI 0.35 to 120.43, favours delayed closure; 1 study, 71 participants); this was very low-certainty evidence. We downgraded the certainty of the evidence for very serious risks of bias because both studies had unclear and high risks of bias. We also downgraded for serious imprecision because effect estimates were imprecise, including the possibility of benefits as well as harms, and very serious imprecision when the data were derived from single small study. These studies reported no other review outcomes. AUTHORS' CONCLUSIONS: We could not determine the risks and benefits of different treatment protocols for open long bone fractures because the evidence was very uncertain for the two comparisons and we did not find any studies addressing the other possible comparisons. Well-designed randomised trials with adequate power are needed to guide surgical and antibiotic treatment of open fractures, particularly with regard to timing and duration of antibiotic administration and timing and staging of surgery.

Videolaryngoscopy versus direct laryngoscopy for adults undergoing tracheal intubation.

BACKGROUND: Tracheal intubation is a common procedure performed to secure the airway in adults undergoing surgery or those who are critically ill. Intubation is sometimes associated with difficulties and complications that may result in patient harm. While it is traditionally achieved by performing direct laryngoscopy, the past three decades have seen the advent of rigid indirect videolaryngoscopes (VLs). A mounting body of evidence comparing the two approaches to tracheal intubation has been acquired over this period of time. This is an update of a Cochrane Review first published in 2016. OBJECTIVES: To assess whether use of different designs of VLs in adults requiring tracheal intubation reduces the failure rate compared with direct laryngoscopy, and assess the benefits and risks of these devices in selected population groups, users and settings. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and Web of Science on 27 February 2021. We also searched clinical trials databases, conference proceedings and conducted forward and backward citation searches. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs with adults undergoing laryngoscopy performed with either a VL or a Macintosh direct laryngoscope (DL) in any clinical setting. We included parallel and cross-over study designs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for the following outcomes: failed intubation, hypoxaemia, successful first attempt at tracheal intubation, oesophageal intubation, dental trauma, Cormack-Lehane grade, and time for tracheal intubation. MAIN RESULTS: We included 222 studies (219 RCTs, three quasi-RCTs) with 26,149 participants undergoing tracheal intubation. Most studies recruited adults undergoing elective surgery requiring tracheal intubation. Twenty-one studies recruited participants with a known or predicted difficult airway, and an additional 25 studies simulated a difficult airway. Twenty-one studies were conducted outside the operating theatre environment; of these, six were in the prehospital setting, seven in the emergency department and eight in the intensive care unit.  We report here the findings of the three main comparisons according to videolaryngoscopy device type. We downgraded the certainty of the outcomes for imprecision, study limitations (e.g. high or unclear risks of bias), inconsistency when we noted substantial levels of statistical heterogeneity and publication bias. Macintosh-style videolaryngoscopy versus direct laryngoscopy (61 studies, 9883 participants) We found moderate-certainty evidence that a Macintosh-style VL probably reduces rates of failed intubation (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.26 to 0.65; 41 studies, 4615 participants) and hypoxaemia (RR 0.72, 95% CI 0.52 to 0.99; 16 studies, 2127 participants). These devices may also increase rates of success on the first intubation attempt (RR 1.05, 95% CI 1.02 to 1.09; 42 studies, 7311 participants; low-certainty evidence) and probably improve glottic view when assessed as Cormack-Lehane grade 3 and 4 (RR 0.38, 95% CI 0.29 to 0.48; 38 studies, 4368 participants; moderate-certainty evidence). We found little or no clear difference in rates of oesophageal intubation (RR 0.51, 95% CI 0.22 to 1.21; 14 studies, 2404 participants) but this finding was supported by low-certainty evidence. We were unsure of the findings for dental trauma because the certainty of this evidence was very low (RR 0.68, 95% CI 0.16 to 2.89; 18 studies, 2297 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I2 = 96%). Hyperangulated videolaryngoscopy versus direct laryngoscopy (96 studies, 11,438 participants) We found moderate-certainty evidence that hyperangulated VLs probably reduce rates of failed intubation (RR 0.51, 95% CI 0.34 to 0.76; 63 studies, 7146 participants) and oesophageal intubation (RR 0.39, 95% CI 0.18 to 0.81; 14 studies, 1968 participants). In subgroup analysis, we noted that hyperangulated VLs were more likely to reduce failed intubation when used on known or predicted difficult airways (RR 0.29, 95% CI 0.17 to 0.48; P = 0.03 for subgroup differences; 15 studies, 1520 participants). We also found that these devices may increase rates of success on the first intubation attempt (RR 1.03, 95% CI 1.00 to 1.05; 66 studies, 8086 participants; low-certainty evidence) and the glottic view is probably also improved (RR 0.15, 95% CI 0.10 to 0.24; 54 studies, 6058 participants; data for Cormack-Lehane grade 3/4 views; moderate-certainty evidence). However, we found low-certainty evidence of little or no clear difference in rates of hypoxaemia (RR 0.49, 95% CI 0.22 to 1.11; 15 studies, 1691 participants), and the findings for dental trauma were unclear because the certainty of this evidence was very low (RR 0.51, 95% CI 0.16 to 1.59; 30 studies, 3497 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I2 = 99%). Channelled videolaryngoscopy versus direct laryngoscopy (73 studies, 7165 participants) We found moderate-certainty evidence that channelled VLs probably reduce rates of failed intubation (RR 0.43, 95% CI 0.30 to 0.61; 53 studies, 5367 participants) and hypoxaemia (RR 0.25, 95% CI 0.12 to 0.50; 15 studies, 1966 participants). They may also increase rates of success on the first intubation attempt (RR 1.10, 95% CI 1.05 to 1.15; 47 studies, 5210 participants; very low-certainty evidence) and probably improve glottic view (RR 0.14, 95% CI 0.09 to 0.21; 40 studies, 3955 participants; data for Cormack-Lehane grade 3/4 views; moderate-certainty evidence). We found little or no clear difference in rates of oesophageal intubation (RR 0.54, 95% CI 0.17 to 1.75; 16 studies, 1756 participants) but this was supported by low-certainty evidence. We were unsure of the findings for dental trauma because the certainty of the evidence was very low (RR 0.52, 95% CI 0.13 to 2.12; 29 studies, 2375 participants). We were not able to pool data for time required for tracheal intubation owing to considerable heterogeneity (I2 = 98%). AUTHORS' CONCLUSIONS: VLs of all designs likely reduce rates of failed intubation and result in higher rates of successful intubation on the first attempt with improved glottic views. Macintosh-style and channelled VLs likely reduce rates of hypoxaemic events, while hyperangulated VLs probably reduce rates of oesophageal intubation. We conclude that videolaryngoscopy likely provides a safer risk profile compared to direct laryngoscopy for all adults undergoing tracheal intubation.

Surgical interventions for treating intracapsular hip fractures in older adults: a network meta-analysis.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a considerable challenge and burden to individuals and healthcare systems. The number of hip fractures globally is rising rapidly. The majority of intracapsular hip fractures are treated surgically. OBJECTIVES: To assess the relative effects (benefits and harms) of all surgical treatments used in the management of intracapsular hip fractures in older adults, using a network meta-analysis of randomised trials, and to generate a hierarchy of interventions according to their outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, and five other databases in July 2020. We also searched clinical trials databases, conference proceedings, reference lists of retrieved articles and conducted backward-citation searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing different treatments for fragility intracapsular hip fractures in older adults. We included total hip arthroplasties (THAs), hemiarthroplasties (HAs), internal fixation, and non-operative treatments. We excluded studies of people with hip fracture with specific pathologies other than osteoporosis or resulting from high-energy trauma. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. One review author completed data extraction which was checked by a second review author. We collected data for three outcomes at different time points: mortality and health-related quality of life (HRQoL) - both reported within 4 months, at 12 months, and after 24 months of surgery, and unplanned return to theatre (at end of study follow-up). We performed a network meta-analysis (NMA) with Stata software, using frequentist methods, and calculated the differences between treatments using risk ratios (RRs) and standardised mean differences (SMDs) and their corresponding 95% confidence intervals (CIs). We also performed direct comparisons using the same codes. MAIN RESULTS: We included 119 studies (102 RCTS, 17 quasi-RCTs) with 17,653 participants with 17,669 intracapsular fractures in the review; 83% of fractures were displaced. The mean participant age ranged from 60 to 87 years and 73% were women.  After discussion with clinical experts, we selected 12 nodes that represented the best balance between clinical plausibility and efficiency of the networks: cemented modern unipolar HA, dynamic fixed angle plate, uncemented first-generation bipolar HA, uncemented modern bipolar HA, cemented modern bipolar HA, uncemented first-generation unipolar HA, uncemented modern unipolar HA, THA with single articulation, dual-mobility THA, pins, screws, and non-operative treatment. Seventy-five studies (with 11,855 participants) with data for at least two of these treatments contributed to the NMA. We selected cemented modern unipolar HA as a reference treatment against which other treatments were compared. This was a common treatment in the networks, providing a clinically appropriate comparison. In order to provide a concise summary of the results, we report only network estimates when there was evidence of difference between treatments. We downgraded the certainty of the evidence for serious and very serious risks of bias and when estimates included possible transitivity, particularly for internal fixation which included more undisplaced fractures. We also downgraded for incoherence, or inconsistency in indirect estimates, although this affected few estimates. Most estimates included the possibility of benefits and harms, and we downgraded the evidence for these treatments for imprecision.  We found that cemented modern unipolar HA, dynamic fixed angle plate and pins seemed to have the greatest likelihood of reducing mortality at 12 months. Overall, 23.5% of participants who received the reference treatment died within 12 months of surgery. Uncemented modern bipolar HA had higher mortality than the reference treatment (RR 1.37, 95% CI 1.02 to 1.85; derived only from indirect evidence; low-certainty evidence), and THA with single articulation also had higher mortality (network estimate RR 1.62, 95% CI 1.13 to 2.32; derived from direct evidence from 2 studies with 225 participants, and indirect evidence; very low-certainty evidence). In the remaining treatments, the certainty of the evidence ranged from low to very low, and we noted no evidence of any differences in mortality at 12 months.  We found that THA (single articulation), cemented modern bipolar HA and uncemented modern bipolar HA seemed to have the greatest likelihood of improving HRQoL at 12 months. This network was comparatively sparse compared to other outcomes and the certainty of the evidence of differences between treatments was very low. We noted no evidence of any differences in HRQoL at 12 months, although estimates were imprecise. We found that arthroplasty treatments seemed to have a greater likelihood of reducing unplanned return to theatre than internal fixation and non-operative treatment. We estimated that 4.3% of participants who received the reference treatment returned to theatre during the study follow-up. Compared to this treatment, we found low-certainty evidence that more participants returned to theatre if they were treated with a dynamic fixed angle plate (network estimate RR 4.63, 95% CI 2.94 to 7.30; from direct evidence from 1 study with 190 participants, and indirect evidence). We found very low-certainty evidence that more participants returned to theatre when treated with pins (RR 4.16, 95% CI 2.53 to 6.84; only from indirect evidence), screws (network estimate RR 5.04, 95% CI 3.25 to 7.82; from direct evidence from 2 studies with 278 participants, and indirect evidence), and non-operative treatment (RR 5.41, 95% CI 1.80 to 16.26; only from indirect evidence). There was very low-certainty evidence of a tendency for an increased risk of unplanned return to theatre for all of the arthroplasty treatments, and in particular for THA, compared with cemented modern unipolar HA, with little evidence to suggest the size of this difference varied strongly between the arthroplasty treatments. AUTHORS' CONCLUSIONS: There was considerable variability in the ranking of each treatment such that there was no one outstanding, or subset of outstanding, superior treatments. However, cemented modern arthroplasties tended to more often yield better outcomes than alternative treatments and may be a more successful approach than internal fixation. There is no evidence of a difference between THA (single articulation) and cemented modern unipolar HA in the outcomes measured in this review. THA may be an appropriate treatment for a subset of people with intracapsular fracture but we have not explored this further.

Arthroplasties for hip fracture in adults.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a huge challenge and burden to individuals and healthcare systems. The number of hip fractures globally is rising rapidly. The majority of hip fractures are treated surgically. This review evaluates evidence for types of arthroplasty: hemiarthroplasties (HAs), which replace part of the hip joint; and total hip arthroplasties (THAs), which replace all of it. OBJECTIVES: To determine the effects of different designs, articulations, and fixation techniques of arthroplasties for treating hip fractures in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, seven other databases and one trials register in July 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing different arthroplasties for treating fragility intracapsular hip fractures in older adults. We included THAs and HAs inserted with or without cement, and comparisons between different articulations, sizes, and types of prostheses. We excluded studies of people with specific pathologies other than osteoporosis and with hip fractures resulting from high-energy trauma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for seven outcomes: activities of daily living, functional status, health-related quality of life, mobility (all early: within four months of surgery), early mortality and at 12 months after surgery, delirium, and unplanned return to theatre at the end of follow-up. MAIN RESULTS: We included 58 studies (50 RCTs, 8 quasi-RCTs) with 10,654 participants with 10,662 fractures. All studies reported intracapsular fractures, except one study of extracapsular fractures. The mean age of participants in the studies ranged from 63 years to 87 years, and 71% were women. We report here the findings of three comparisons that represent the most substantial body of evidence in the review. Other comparisons were also reported, but with many fewer participants. All studies had unclear risks of bias in at least one domain and were at high risk of detection bias. We downgraded the certainty of many outcomes for imprecision, and for risks of bias where sensitivity analysis indicated that bias sometimes influenced the size or direction of the effect estimate. HA: cemented versus uncemented (17 studies, 3644 participants) There was moderate-certainty evidence of a benefit with cemented HA consistent with clinically small to large differences in health-related quality of life (HRQoL) (standardised mean difference (SMD) 0.20, 95% CI 0.07 to 0.34; 3 studies, 1122 participants), and reduction in the risk of mortality at 12 months (RR 0.86, 95% CI 0.78 to 0.96; 15 studies, 3727 participants). We found moderate-certainty evidence of little or no difference in performance of activities of daily living (ADL) (SMD -0.03, 95% CI -0.21 to 0.16; 4 studies, 1275 participants), and independent mobility (RR 1.04, 95% CI 0.95 to 1.14; 3 studies, 980 participants). We found low-certainty evidence of little or no difference in delirium (RR 1.06, 95% CI 0.55 to 2.06; 2 studies, 800 participants), early mortality (RR 0.95, 95% CI 0.80 to 1.13; 12 studies, 3136 participants) or unplanned return to theatre (RR 0.70, 95% CI 0.45 to 1.10; 6 studies, 2336 participants). For functional status, there was very low-certainty evidence showing no clinically important differences. The risks of most adverse events were similar. However, cemented HAs led to less periprosthetic fractures intraoperatively (RR 0.20, 95% CI 0.08 to 0.46; 7 studies, 1669 participants) and postoperatively (RR 0.29, 95% CI 0.14 to 0.57; 6 studies, 2819 participants), but had a higher risk of pulmonary embolus (RR 3.56, 95% CI 1.26 to 10.11, 6 studies, 2499 participants). Bipolar HA versus unipolar HA (13 studies, 1499 participants) We found low-certainty evidence of little or no difference between bipolar and unipolar HAs in early mortality (RR 0.94, 95% CI 0.54 to 1.64; 4 studies, 573 participants) and 12-month mortality (RR 1.17, 95% CI 0.89 to 1.53; 8 studies, 839 participants). We are unsure of the effect for delirium, HRQoL, and unplanned return to theatre, which all indicated little or no difference between articulation, because the certainty of the evidence was very low. No studies reported on early ADL, functional status and mobility. The overall risk of adverse events was similar. The absolute risk of dislocation was low (approximately 1.6%) and there was no evidence of any difference between treatments. THA versus HA (17 studies, 3232 participants) The difference in the risk of mortality at 12 months was consistent with clinically relevant benefits and harms (RR 1.00, 95% CI 0.83 to 1.22; 11 studies, 2667 participants; moderate-certainty evidence). There was no evidence of a difference in unplanned return to theatre, but this effect estimate includes clinically relevant benefits of THA (RR 0.63, 95% CI 0.37 to 1.07, favours THA; 10 studies, 2594 participants; low-certainty evidence). We found low-certainty evidence of little or no difference between THA and HA in delirium (RR 1.41, 95% CI 0.60 to 3.33; 2 studies, 357 participants), and mobility (MD -0.40, 95% CI -0.96 to 0.16, favours THA; 1 study, 83 participants). We are unsure of the effect for early functional status, ADL, HRQoL, and mortality, which indicated little or no difference between interventions, because the certainty of the evidence was very low.  The overall risks of adverse events were similar. There was an increased risk of dislocation with THA (RR 1.96, 95% CI 1.17 to 3.27; 12 studies, 2719 participants) and no evidence of a difference in deep infection. AUTHORS' CONCLUSIONS: For people undergoing HA for intracapsular hip fracture, it is likely that a cemented prosthesis will yield an improved global outcome, particularly in terms of HRQoL and mortality. There is no evidence to suggest a bipolar HA is superior to a unipolar prosthesis. Any benefit of THA compared with hemiarthroplasty is likely to be small and not clinically appreciable. We encourage researchers to focus on alternative implants in current clinical practice, such as dual-mobility bearings, for which there is limited available evidence.

Surgical interventions for treating extracapsular hip fractures in older adults: a network meta-analysis.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a challenge and burden to individuals and healthcare systems. The number of hip fractures globally is rising. The majority of extracapsular hip fractures are treated surgically. OBJECTIVES: To assess the relative effects (benefits and harms) of all surgical treatments used in the management of extracapsular hip fractures in older adults, using a network meta-analysis of randomised trials, and to generate a hierarchy of interventions according to their outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science and five other databases in July 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing different treatments for fragility extracapsular hip fractures in older adults. We included internal and external fixation, arthroplasties and non-operative treatment. We excluded studies of hip fractures with specific pathologies other than osteoporosis or resulting from high-energy trauma. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. One review author completed data extraction which was checked by a second review author. We collected data for three outcomes at different time points: mortality and health-related quality of life (HRQoL) - both reported within 4 months, at 12 months and after 24 months of surgery, and unplanned return to theatre (at end of study follow-up). We performed a network meta-analysis (NMA) with Stata software, using frequentist methods, and calculated the differences between treatments using risk ratios (RRs) and standardised mean differences (SMDs) and their corresponding 95% confidence intervals (CIs). We also performed direct comparisons using the same codes. MAIN RESULTS: We included 184 studies (160 RCTs and 24 quasi-RCTs) with 26,073 participants with 26,086 extracapsular hip fractures in the review. The mean age in most studies ranged from 60 to 93 years, and 69% were women. After discussion with clinical experts, we selected nine nodes that represented the best balance between clinical plausibility and efficiency of the networks: fixed angle plate (dynamic and static), cephalomedullary nail (short and long), condylocephalic nail, external fixation, hemiarthroplasty, total hip arthroplasty (THA) and non-operative treatment. Seventy-three studies (with 11,126 participants) with data for at least two of these treatments contributed to the NMA. We selected the dynamic fixed angle plate as a reference treatment against which other treatments were compared. This was a common treatment in the networks, providing a clinically appropriate comparison.  We downgraded the certainty of the evidence for serious and very serious risks of bias, and because some of the estimates included the possibility of transitivity owing to the proportion of stable and unstable fractures between treatment comparisons. We also downgraded if we noted evidence of inconsistency in direct or indirect estimates from which the network estimate was derived. Most estimates included the possibility of benefits and harms, and we downgraded the evidence for these treatments for imprecision.  Overall, 20.2% of participants who received the reference treatment had died by 12 months after surgery. We noted no evidence of any differences in mortality at this time point between the treatments compared. Effect estimates of all treatments included plausible benefits as well as harms. Short cephalomedullary nails had the narrowest confidence interval (CI), with 7 fewer deaths (26 fewer to 15 more) per 1000 participants, compared to the reference treatment (risk ratio (RR) 0.97, 95% CI 0.87 to 1.07). THA had the widest CI, with 62 fewer deaths (177 fewer to 610 more) per 1000 participants, compared to the reference treatment (RR 0.69, 95% CI 0.12 to 4.03). The certainty of the evidence for all treatments was low to very low. Although we ranked the treatments, this ranking should be interpreted cautiously because of the imprecision in all the network estimates for these treatments. Overall, 4.3% of participants who received the reference treatment had unplanned return to theatre. Compared to this treatment, we found very low-certainty evidence that 58 more participants (14 to 137 more) per 1000 participants returned to theatre if they were treated with a static fixed angle plate (RR 2.48, 95% CI 1.36 to 4.50), and 91 more participants (37 to 182 more) per 1000 participants returned to theatre if treated with a condylocephalic nail (RR 3.33, 95% CI 1.95 to 5.68). We also found that these treatments were ranked as having the highest probability of unplanned return to theatre. In the remaining treatments, we noted no evidence of any differences in unplanned return to theatre, with effect estimates including benefits as well as harms. The certainty of the evidence for these other treatments ranged from low to very low. We did not use GRADE to assess the certainty of the evidence for early mortality, but our findings were similar to those for 12-month mortality, with no evidence of any differences in treatments when compared to dynamic fixed angle plate. Very few studies reported HRQoL and we were unable to build networks from these studies and perform network meta-analysis.  AUTHORS' CONCLUSIONS: Across the networks, we found that there was considerable variability in the ranking of each treatment such that there was no one outstanding, or subset of outstanding, superior treatments. However, static implants such as condylocephalic nails and static fixed angle plates did yield a higher risk of unplanned return to theatre. We had insufficient evidence to determine the effects of any treatments on HRQoL, and this review includes data for only two outcomes. More detailed pairwise comparisons of some of the included treatments are reported in other Cochrane Reviews in this series. Short cephalomedullary nails versus dynamic fixed angle plates contributed the most evidence to each network, and our findings indicate that there may be no difference between these treatments. These data included people with both stable and unstable extracapsular fractures. At this time, there are too few studies to draw any conclusions regarding the benefits or harms of arthroplasty or external fixation for extracapsular fracture in older adults. Future research could focus on the benefits and harms of arthroplasty interventions compared with internal fixation using a dynamic implant.

Cephalomedullary nails versus extramedullary implants for extracapsular hip fractures in older adults.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a substantial challenge and burden to patients, healthcare systems and society. The increased proportion of older adults in the world population means that the absolute number of hip fractures is rising rapidly across the globe. Most hip fractures are treated surgically. This Cochrane Review evaluates evidence for implants used to treat extracapsular hip fractures. OBJECTIVES: To assess the relative effects of cephalomedullary nails versus extramedullary fixation implants for treating extracapsular hip fractures in older adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, the Cochrane Database of Systematic Reviews, Epistemonikos, ProQuest Dissertations & Theses, and the National Technical Information Service in July 2020. We also searched clinical trials databases, conference proceedings, reference lists of retrieved articles, and conducted backward-citation searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing cephalomedullary nails with extramedullary implants for treating fragility extracapsular hip fractures in older adults. We excluded studies in which all or most fractures were caused by a high-energy trauma or specific pathologies other than osteoporosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for seven critical outcomes: performance of activities of daily living (ADL), delirium, functional status, health-related quality of life, mobility, mortality (reported within four months of surgery as 'early mortality'; and reported from four months onwards, with priority given to data at 12 months, as '12 months since surgery'), and unplanned return to theatre for treating a complication resulting directly or indirectly from the primary procedure (such as deep infection or non-union). We assessed the certainty of the evidence for these outcomes using GRADE.  MAIN RESULTS: We included 76 studies (66 RCTs, 10 quasi-RCTs) with a total of 10,979 participants with 10,988 extracapsular hip fractures. The mean ages of participants in the studies ranged from 54 to 85 years; 72% were women. Seventeen studies included unstable trochanteric fractures; three included stable trochanteric fractures only; one included only subtrochanteric fractures; and other studies included a mix of fracture types. More than half of the studies were conducted before 2010. Owing to limitations in the quality of reporting, we could not easily judge whether care pathways in these older studies were comparable to current standards of care. We downgraded the certainty of the outcomes because of high or unclear risk of bias; imprecision (when data were available from insufficient numbers of participants or the confidence interval (CI) was wide); and inconsistency (when we noted substantial levels of statistical heterogeneity or differences between findings when outcomes were reported using other measurement tools). There is probably little or no difference between cephalomedullary nails and extramedullary implants in terms of mortality within four months of surgery (risk ratio (RR) 0.96, 95% CI 0.79 to 1.18; 30 studies, 4603 participants) and at 12 months (RR 0.99, 95% CI 0.90 to 1.08; 47 studies, 7618 participants); this evidence was assessed to be of moderate certainty. We found low-certainty evidence for differences in unplanned return to theatre but this was imprecise and included clinically relevant benefits and harms (RR 1.15, 95% CI 0.89 to 1.50; 50 studies, 8398 participants). The effect estimate for functional status at four months also included clinically relevant benefits and harms; this evidence was derived from only two small studies and was imprecise (standardised mean difference (SMD) 0.02, 95% CI -0.27 to 0.30; 188 participants; low-certainty evidence). Similarly, the estimate for delirium was imprecise (RR 1.22, 95% CI 0.67 to 2.22; 5 studies, 1310 participants; low-certainty evidence). Mobility at four months was reported using different measures (such as the number of people with independent mobility or scores on a mobility scale); findings were not consistent between these measures and we could not be certain of the evidence for this outcome. We were also uncertain of the findings for performance in ADL at four months; we did not pool the data from four studies because of substantial heterogeneity. We found no data for health-related quality of life at four months. Using a cephalomedullary nail in preference to an extramedullary device saves one superficial infection per 303 patients (RR 0.71, 95% CI 0.53 to 0.96; 35 studies, 5087 participants; moderate-certainty evidence) and leads to fewer non-unions (RR 0.55, 95% CI 0.32 to 0.96; 40 studies, 4959 participants; moderate-certainty evidence). However, the risk of intraoperative implant-related fractures was greater with cephalomedullary nails (RR 2.94, 95% CI 1.65 to 5.24; 35 studies, 4872 participants; moderate-certainty evidence), as was the risk of later fractures (RR 3.62, 95% CI 2.07 to 6.33; 46 studies, 7021 participants; moderate-certainty evidence). Cephalomedullary nails caused one additional implant-related fracture per 67 participants. We noted no evidence of a difference in other adverse events related or unrelated to the implant, fracture or both. Subgroup analyses provided no evidence of differences between the length of cephalomedullary nail used, the stability of the fracture, or between newer and older designs of cephalomedullary nail. AUTHORS' CONCLUSIONS: Extramedullary devices, most commonly the sliding hip screw, yield very similar functional outcomes to cephalomedullary devices in the management of extracapsular fragility hip fractures. There is a reduced risk of infection and non-union with cephalomedullary nails, however there is an increased risk of implant-related fracture that is not attenuated with newer designs. Few studies considered patient-relevant outcomes such as performance of activities of daily living, health-related quality of life, mobility, or delirium. This emphasises the need to include the core outcome set for hip fracture in future RCTs.

Internal fixation implants for intracapsular hip fractures in older adults.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a huge challenge and burden to patients, healthcare systems and society. The increased proportion of older adults in the world population means that the absolute number of hip fractures is rising rapidly across the globe. The majority of hip fractures are treated surgically. This review evaluates evidence for types of internal fixation implants used in joint-preserving surgery for intracapsular hip fractures. OBJECTIVES: To determine the relative effects (benefits and harms) of different implants for the internal fixation of intracapsular hip fractures in older adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, Cochrane Database of Systematic Reviews, Epistemonikos, Proquest Dissertations and Theses, and National Technical Information Service in July 2020. We also searched clinical trials databases, conference proceedings, reference lists of retrieved articles and conducted backward-citation searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing implants used for internal fixation of fragility intracapsular proximal femoral fractures in older adults. Types of implants were smooth pins (these include pins with fold-out hooks), screws, or fixed angle plates. We excluded studies in which all or most fractures were caused by specific pathologies other than osteoporosis or were the result of a high energy trauma. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. One review author extracted data and assessed risk of bias which was checked by a second review author. We collected data for seven outcomes: activities of daily living (ADL), delirium, functional status, health-related quality of life (HRQoL), mobility, mortality (reported within four months of surgery as early mortality, and at 12 months since surgery), and unplanned return to theatre for treating a complication resulting directly or indirectly from the primary procedure (such as deep infection or non-union). We assessed the certainty of the evidence for these outcomes using GRADE. MAIN RESULTS: We included 38 studies (32 RCTs, six quasi-RCTs) with 8585 participants with 8590 intracapsular fractures. The mean ages of participants in the studies ranged from 60 to 84 years; 73% were women, and 38% of fractures were undisplaced. We report here the findings of the four main comparisons, which were between different categories of implants. We downgraded the certainty of the outcomes for imprecision (when data were available from insufficient numbers of participants or the confidence interval (CI) was wide), study limitations (e.g. high or unclear risks of bias), and inconsistency (when we noted substantial levels of statistical heterogeneity). Smooth pins versus fixed angle plate (four studies, 1313 participants) We found very low-certainty evidence of little or no difference between the two implant types in independent mobility with no more than one walking stick (1 study, 112 participants), early mortality (1 study, 383 participants), mortality at 12 months (2 studies, 661 participants), and unplanned return to theatre (3 studies, 736 participants). No studies reported on ADL, delirium, functional status, or HRQoL. Screws versus fixed angle plates (11 studies, 2471 participants) We found low-certainty evidence of no clinically important differences between the two implant types in functional status using WOMAC (MD -3.18, 95% CI -6.35 to -0.01; 2 studies, 498 participants; range of scores from 0 to 96, lower values indicate better function), and HRQoL using EQ-5D (MD 0.03, 95% CI 0.00 to 0.06; 2 studies, 521 participants; range -0.654 (worst), 0 (dead), 1 (best)). We also found low-certainty evidence showing little or no difference between the two implant types in mortality at 12 months (RR 1.04, 95% CI 0.83 to 1.31; 7 studies, 1690 participants), and unplanned return to theatre (RR 1.10, 95% CI 0.95 to 1.26; 11 studies, 2321 participants). We found very low-certainty evidence of little or no difference between the two implant types in independent mobility (1 study, 70 participants), and early mortality (3 studies, 467 participants). No studies reported on ADL or delirium. Screws versus smooth pins (seven studies, 1119 participants) We found low-certainty evidence of no or little difference between the two implant types in mortality at 12 months (RR 1.07, 95% CI 0.85 to 1.35; 6 studies, 1005 participants; low-certainty evidence). We found very low-certainty evidence of little or no difference between the two implant types in early mortality (3 studies, 584 participants) and unplanned return to theatre (5 studies, 862 participants). No studies reported on ADL, delirium, functional status, HRQoL, or mobility. Screws or smooth pins versus fixed angle plates (15 studies, 3784 participants) In this comparison, we combined data from the first two comparison groups. We found low-certainty evidence of no or little difference between the two groups of implants in mortality at 12 months (RR 1.04, 95% CI.083 to 1.31; 7 studies, 1690 participants) and unplanned return to theatre (RR 1.02, 95% CI 0.88 to 1.18; 14 studies, 3057 participants). We found very low-certainty evidence of little or no difference between the two groups of implants in independent mobility (2 studies, 182 participants), and early mortality (4 studies, 850 participants). We found no additional evidence to support the findings for functional status or HRQoL as reported in 'Screws versus fixed angle plates'. No studies reported ADL or delirium. AUTHORS' CONCLUSIONS: There is low-certainty evidence that there may be little or no difference between screws and fixed angle plates in functional status, HRQoL, mortality at 12 months, or unplanned return to theatre; and between screws and pins in mortality at 12 months. The limited and very low-certainty evidence for the outcomes for which data were available for the smooth pins versus fixed angle plates comparison, as well as the other outcomes for which data were available for the screws and fixed angle plates, and screws and pins comparisons means we have very little confidence in the estimates of effect for these outcomes. Additional RCTs would increase the certainty of the evidence. We encourage such studies to report outcomes consistent with the core outcome set for hip fracture, including long-term quality of life indicators such as ADL and mobility.

High-flow nasal cannulae for respiratory support in adult intensive care patients.

BACKGROUND: High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review. OBJECTIVES: To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches. SELECTION CRITERIA: We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO2/FiO2 may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma. AUTHORS' CONCLUSIONS: HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.

ANTECEDENTES: Las cánulas nasales de alto flujo (HFNC) administran flujos elevados de una mezcla humedecida de aire y oxígeno a través de cánulas nasales de gran calibre y pueden ser útiles para proporcionar asistencia respiratoria a los adultos que presentan insuficiencia respiratoria aguda, o que tienen riesgo de presentarla, en la unidad de cuidados intensivos (UCI). Esta es una actualización de una versión anterior de la revisión. OBJETIVOS: Evaluar la eficacia de las HFNC en comparación con la oxigenoterapia estándar, o la ventilación no invasiva (VNI) o la ventilación con presión positiva no invasiva (VPPNI), para la asistencia respiratoria de adultos en la UCI. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL, MEDLINE, Embase, CINAHL, Web of Science y en el Registro Cochrane de covid­19 (17 de abril de 2020), registros de ensayos clínicos (6 de abril de 2020) y se realizaron búsquedas de citas prospectivas y retrospectivas. CRITERIOS DE SELECCIÓN: Se incluyeron los estudios controlados aleatorizados (ECA) con un diseño de grupos paralelos o cruzados que compararon el uso de HFNC versus otro tipo de asistencia respiratoria no invasiva (oxigenoterapia estándar a través de cánulas nasales o mascarilla; o VNI o VPPNI que incluía la presión positiva continua en las vías respiratorias y la presión positiva de dos niveles en las vías respiratorias) en adultos ingresados en la UCI. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los procedimientos metodológicos estándar previstos por la Colaboración Cochrane. RESULTADOS PRINCIPALES: Se incluyeron 31 estudios (22 de grupos paralelos y nueve de diseño cruzado) con 5136 participantes; esta actualización incluyó 20 estudios nuevos. Veintiún estudios compararon la HFNC con la oxigenoterapia estándar, y 13 compararon la HFNC con la VNI o la VPPNI; tres estudios incluyeron ambas comparaciones. Se encontraron 51 estudios en curso (con una estimación de 12 807 participantes) y 19 estudios en espera de clasificación en los que no fue posible determinar la información de elegibilidad del estudio. En 18 estudios el tratamiento se inició después de la extubación. En el resto de los estudios, los participantes no habían recibido de forma previa ventilación mecánica. HFNC versus oxigenoterapia estándar La HFNC podría conducir a un menor fracaso del tratamiento, según lo indicado por el escalamiento a tipos alternativos de oxigenoterapia (razón de riesgos [RR] 0,62; intervalo de confianza [IC] del 95%: 0,45 a 0,86; 15 estudios, 3044 participantes; evidencia de certeza baja). La HFNC probablemente da lugar a poca o ninguna diferencia en la mortalidad cuando se compara con la oxigenoterapia estándar (RR 0,96; IC del 95%: 0,82 a 1,11; 11 estudios, 2673 participantes; evidencia de certeza moderada). La HFNC probablemente da lugar a poca o ninguna diferencia con respecto a los casos de neumonía (RR 0,72; IC del 95%: 0,48 a 1,09; cuatro estudios, 1057 participantes; evidencia de certeza moderada), y no se sabe con certeza su efecto sobre la mucosa nasal ni el traumatismo cutáneo (RR 3,66; IC del 95%: 0,43 a 31,48; dos estudios, 617 participantes; evidencia de certeza muy baja). Se encontró evidencia de certeza baja de que la HFNC podría dar lugar a poca o ninguna diferencia en la duración de la estancia en la UCI según el tipo de asistencia respiratoria utilizada (DM 0,12 días; IC del 95%: ­0,03 a 0,27; siete estudios, 1014 participantes). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en el cociente entre la presión parcial de oxígeno arterial y la fracción de oxígeno inspirado (PaO2/FiO2) en las primeras 24 horas del tratamiento (DM 10,34 mmHg; IC del 95%: ­17,31 a 38; cinco estudios, 600 participantes; evidencia de certeza muy baja). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en la comodidad a corto plazo (DM 0,31; IC del 95%: ­0,60 a 1,22; cuatro estudios, 662 participantes, evidencia de certeza muy baja), o en la comodidad a largo plazo (DM 0,59; IC del 95%: ­2,29 a 3,47; dos estudios, 445 participantes, evidencia de certeza muy baja). HFNC versus VNI o VPPNI No se encontró evidencia de una diferencia entre los grupos en el fracaso del tratamiento cuando se utilizó la HFNC después de la extubación o sin el uso previo de ventilación mecánica (RR 0,98; IC del 95%: 0,78 a 1,22; cinco estudios, 1758 participantes; evidencia de certeza baja), ni en la mortalidad hospitalaria (RR 0,92; IC del 95%: 0,64 a 1,31; cinco estudios, 1758 participantes; evidencia de certeza baja). No hay certeza sobre el efecto del uso de la HFNC en la incidencia de la neumonía (RR 0,51; IC del 95%: 0,17 a 1,52; tres estudios, 1750 participantes; evidencia de certeza muy baja), y la HFNC podría dar lugar a poca o ninguna diferencia en el barotraumatismo (RR 1,15; IC del 95%: 0,42 a 3,14; un estudio, 830 participantes; evidencia de certeza baja). La HFNC podría suponer una diferencia escasa o nula en la duración de la estancia en la UCI (DM ­0,72 días; IC del 95%: ­2,85 a 1,42; dos estudios, 246 participantes; evidencia de certeza baja). El cociente PaO2/FiO2 podría ser menor hasta 24 horas con el uso de la HFNC (DM ­58,10 mmHg; IC del 95%: ­71,68 a ­44,51; tres estudios, 1086 participantes; evidencia de certeza baja). No se sabe si la HFNC mejoró la comodidad a corto plazo cuando se midió mediante puntuaciones de comodidad (DM 1,33; IC del 95%: 0,74 a 1,92; dos estudios, 258 participantes) y respuestas a cuestionarios (RR 1,30; IC del 95%: 1,10 a 1,53; un estudio, 168 participantes); la evidencia para la comodidad a corto plazo fue de certeza muy baja. Ningún estudio informó sobre la mucosa nasal ni el traumatismo cutáneo. CONCLUSIONES DE LOS AUTORES: La HFNC podría dar lugar a un menor fracaso del tratamiento en comparación con la oxigenoterapia estándar, pero probablemente suponga una escasa o nula diferencia en el fracaso del tratamiento en comparación con la VNI o la VPPNI. Para la mayoría de los demás desenlaces de la revisión, no se encontró evidencia de una diferencia en el efecto. Sin embargo, la certeza de la evidencia se consideró baja o muy baja. Se encontró un gran número de estudios en curso; incluirlos en futuras actualizaciones podría aumentar la certeza o podría alterar la dirección de estos efectos.

Interventions to reduce body temperature to 35 °C to 37 °C in adults and children with traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability, with an estimated 5.5 million people experiencing severe TBI worldwide every year. Observational clinical studies of people with TBI suggest an association between raised body temperature and unfavourable outcome, although this relationship is inconsistent. Additionally, preclinical models suggest that reducing temperature to 35 °C to 37.5 °C improves biochemical and histopathological outcomes compared to reducing temperature to a lower threshold of 33 °C to 35 °C. It is unknown whether reducing body temperature to 35 °C to 37.5 °C in people admitted to hospital with TBI is beneficial, has no effect, or causes harm. This is an update of a review last published in 2014. OBJECTIVES: To assess the effects of pharmacological interventions or physical interventions given with the intention of reducing body temperature to 35 °C to 37.5 °C in adults and children admitted to hospital after TBI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and PubMed on 28 November 2019. We searched clinical trials registers, grey literature and references lists of reviews, and we carried out forward citation searches of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with participants of any age admitted to hospital following TBI. We included interventions that aimed to reduce body temperature to 35 °C to 37.5 °C: these included pharmacological interventions (such as paracetamol, or non-steroidal anti-inflammatory drugs), or physical interventions (such as surface cooling devices, bedside fans, or cooled intravenous fluids). Eligible comparators were placebo or usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of the evidence with GRADE. MAIN RESULTS: We included one RCT with 41 participants. This study recruited adult participants admitted to two intensive care units in Australia, and evaluated a pharmacological intervention. Researchers gave participants 1 g paracetamol or a placebo intravenously at four-hourly intervals for 72 hours. We could not be certain whether intravenous paracetamol influenced mortality at 28 days (risk ratio 2.86, 95% confidence interval 0.32 to 25.24). We judged the evidence for this outcome to be very low certainty, meaning we have very little confidence in this effect estimate, and the true result may be substantially different to this effect. We downgraded the certainty for imprecision (because the evidence was from a single study with very few participants), and study limitations (because we noted a high risk of selective reporting bias). This study was otherwise at low risk of bias. The included study did not report the primary outcome for this review, which was the number of people with a poor outcome at the end of follow-up (defined as death or dependency, as measured on a scale such as the Glasgow Outcome Score), or any of our secondary outcomes, which included the number of people with further intracranial haemorrhage, extracranial haemorrhage, abnormal intracranial pressure, or pneumonia or other serious infections. The only other completed trial that we found was of a physical intervention that compared advanced fever control (using a surface cooling device) versus conventional fever control in 12 participants. The trial was published as an abstract only, with insufficient details to allow inclusion, so we have added this to the 'studies awaiting classification' section, pending further information from the study authors or publication of the full study report. We identified four ongoing studies that will contribute evidence to future updates of the review if they measure relevant outcomes and, in studies with a mixed population, report data separately for participants with TBI. AUTHORS' CONCLUSIONS: One small study contributed very low-certainty evidence for mortality to this review. The uncertainty is largely driven by limited research into reduction of body temperature to 35 °C to 37.5 °C in people with TBI. Further research that evaluates pharmacological or physical interventions, or both, may increase certainty in this field. We propose that future updates of the review, and ongoing and future research in this field, incorporate outcomes that are important to the people receiving the interventions, including side effects of any pharmacological agent (e.g. nausea or vomiting), and discomfort caused by physical therapies.