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Background Pulmonary transplantation is the final treatment option for people with end-stage respiratory diseases. Evidence suggests that exercise training may contribute to speeding up physical recovery in adults undergoing lung transplantation, helping to minimize or resolve impairments due to physical inactivity in both the pre- and post-transplant stages. However, there is a lack of detailed guidelines on how exercise training should be carried out in this specific sub-population. Objectives To determine the benefits and safety of exercise training in adult patients who have undergone lung transplantation, measuring the maximal and functional exercise capacity; health-related quality of life; adverse events; patient readmission; pulmonary function; muscular strength; pathological bone fractures; return to normal activities and death. Search methods We searched the Cochrane Kidney and Transplant Specialised Register up to 6 October 2020 using relevant search terms for this review. Studies in the CKTR are identified through CENTRAL, MEDLINE, and EMBASE searches, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov . Selection criteria Randomised controlled trials (RCTs) were included comparing exercise training with usual care or no exercise training, or with another exercise training program in terms of dosage, modality, program length, or use of supporting exercise devices. The study population comprised of participants older than 18 yearswho underwent lung transplantation independent of their underlying respiratory pathology. Data collection and analysis Two authors independently reviewed all records identified by the search strategy and selected studies that met the eligibility criteria for inclusion in this review. In the first instance, the disagreements were resolved by consensus, and if this was not possible the decision was taken by a third reviewer. The same reviewers independently extracted outcome data from included studies and assessed risk of bias. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results Eight RCTs (438 participants) were included in this review. The median sample size was 60 participants with a range from 16 to 83 participants. The mean age of participants was 54.9 years and 51.9% of the participants were male. The median duration of the exercise training programs for the groups undergoing the intervention was 13 weeks, and the median duration of training in the active control groups was four weeks. Overall the risk of bias was considered to be high, mainly due to the inability to blind the study participants and the selective reporting of the results. Due to small number of studies included in this review, and the heterogeneity of the intervention and outcomes, we did not obtain a summary estimate of the results. Two studies comparing resistance exercise training with no exercise reported increases in muscle strength and bone mineral density (surrogate outcomes for pathological bone fractures) with exercise training (P > 0.05), but no differences in adverse events. Exercise capacity, health-related quality of life (HRQoL), pulmonary function, and death (any cause) were not reported. Three studies compared two different resistant training programs. Two studies comparing squats using a vibration platform (WBVT) compared to squats on the floor reported an improvement in 6-minute walk test (6MWT) (28.4 metres, 95% CI 3 to 53.7; P = 0.029; and 28.3 metres, 95% CI 10.0 to 46.6; P < 0.05) with the WBVT. Supervised upper limb exercise (SULP) program improved 6MWT at 6 months compared to no supervised upper limb exercise (NULP) (SULP group: 561.2 +/- 83.6 metres; NULP group: 503.5 +/- 115.2 metres; P = 0.01). There were no differences in HRQoL, adverse events, muscular strength, or death (any cause). Pulmonary function and pathological bone fractures were not reported. Two studies comparing multimodal exercise training with no exercise reported improvement in 6MWT at 3 months (P = 0.008) and at 12-months post-transplant (P = 0.002) and muscular strength (quadriceps force (P = 0.001); maximum leg press (P = 0.047)) with multimodal exercise, but no improvement in HRQoL, adverse events, pulmonary function, pathological bone fractures (lumbar T-score), or death (any cause). One study comparing the same multimodal exercise programs given over 7 and 14 weeks reported no differences in 6MWT, HRQoL, adverse events, pulmonary function, muscle strength, or death (any cause). Pathological bone fractures were not reported. According to GRADE criteria, we rated the certainty of the evidence as very low, mainly due to the high risk of bias and serious imprecision. Authors' conclusions In adults undergoing lung transplantation the evidence about the effects of exercise training is very uncertain in terms of maximal and functional exercise capacity, HRQoL and safety, due to very imprecise estimates of effects and high risk of bias.

Objectives The aim of this study was to conduct a systematic review in order to assess the impact of early childhood caries (ECC) and its severity on Oral health-related quality of life (OHRQoL). Materials and methods An electronic search was conducted in MEDLINE, EMBASE, Cochrane, SciELO and Lilacs databases. The study eligibility criteria were primary studies published in English, Spanish or Portuguese that assessed OHRQoL in preschool children with dental caries using validated instruments. Two researchers independently performed the selection process and data extraction. The Effective Public Health Practice Project's Quality Assessment Tool was used for the quality assessment. Random effects models were used to estimate the pooled effect for continuous and categorical data. Results Of 2,037 identified articles, thirty-five studies (37 articles) met the inclusion criteria. The methodological quality was judged mainly as moderate. Children with ECC were more likely to report any impact on OHRQoL than children without caries (OR: 1.99; 95% CI: 1.51-2.62; 6 studies). Severe ECC (dmft > 5) presented a higher effect (OR: 5.00; 95% CI: 3.70-6.74; 8 studies). Sensitivity analysis including only population studies showed uncertain results on the impact of ECC on OHRQoL (OR: 1.67; 95% CI: 0.99-2.82; I2 = 95%). The symptom and psychological domains were the most affected (SMD: 0.60, 95% CI: 0.38-0.81 and SMD: 0.61, 95% CI: 0.37-0.85 respectively). Conclusions ECC has a negative impact on the OHRQoL of both preschoolers and their families. However, its impact on OHRQoL is diluted when it is evaluated at population level.

Background Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. Objectives To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. Search methods For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). Selection criteria Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. Data collection and analysis Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I-2). Additionally, we performed sensitivity analyses. Main results We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I-2 = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I-2 = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I-2 = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I-2 = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to -2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I-2 = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. Authors' conclusions Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.

This protocol has been withdrawn from publication.

Background Red blood cell (RBC) transfusions are essential in health care. The quality of recommendations included in clinical practice guidelines (CPG), regarding this intervention, has not been systematically evaluated. This paper systematically assessed CPGs for RBC‐transfusion, to appraise their methodological quality, to explore changes in quality over time, and to assess the consistency of the hemoglobin threshold (HT) recommendations. Methods We searched for CPGs that included recommendations of RBC‐transfusion in generic databases, compiler entities, registries, clearinghouses and guideline developers. Three reviewers extracted data on CPGs characteristics and HT recommendations, independently appraised the quality of the studies using AGREE II and resolved disagreements by consensus. Results We examined 16 CPGs. Mean scores (mean ± SD) were: scope and purpose (59.4% ± 19.8%), stakeholder involvement (43.2% ± 22.6%), rigor of development (50% ± 25%), clarity of presentation (74.4% ± 12.6%), applicability (19.4% ± 18.8%), and editorial independence (41% ± 30%). Seven CPGs recommended a restrictive strategy for RBC transfusion; four CPGs gave a guarded statement considering an HT of 7 g/dL, as safe to prescribe an RBC transfusion. Eight CPGs did not provide an HT stating that RBC transfusions should not be prescribed by HT alone. Conclusions Only 3 out of the 16 evaluated CPGs were “recommended” by the independent evaluators. Four domains “stakeholder involvement,” “rigor of development,” applicability,” and “editorial independence” had serious shortcomings. Recommendations about the use of an HT for RBC‐transfusion were heterogeneous among guidelines. Greater efforts are needed to provide high‐quality CPGs in the RBC‐transfusion practice.

Objectives The objective of the study was to develop and validate an adequate tool to evaluate the risk of bias of randomized controlled trials, observational studies, and systematic reviews assessing drug adverse events. Study Design and Setting We developed a structured risk of bias checklist applicable to randomized trials, cohort, case–control and nested case–control studies, and systematic reviews focusing on drug safety. Face and content validity was judged by three experienced reviewers. Interrater and intrarater reliability were determined using 20 randomly selected studies, assessed by three other independent reviewers including one performing a 3-week retest. Results The developed checklist examines eight domains: study design and objectives, selection bias, attrition, adverse events information bias, other information bias, statistical methods to control confounding, other statistical methods, and conflicts of interest. The total number of questions varied from 10 to 32 depending on the study design. Interrater and intrarater agreements were fair with Kendall's W of 0.70 and 0.74, respectively. Median time to complete the checklist was 8.5 minutes. Conclusion The developed checklist showed face and content validity and acceptable reliability to assess the risk of bias for studies analyzing drug adverse events. Hence, it might be considered as a novel useful tool for systematic reviews and meta-analyses focusing on drug safety.

To determine the prevalence and magnitude of medication errors and their association with patients' sociodemographic and clinical characteristics and nurses' work conditions.An observational, analytical, cross-sectional and ambispective study was conducted in critically ill adult patients.Data concerning prescription errors were collected retrospectively from medical records and administration errors were identified through direct observation of nurses during drug administration. Those data were collected between April and July 2015.A total of 650 prescription errors were identified for 961 drugs in 90 patients (mean error 7[SD 4.1] per patient) and prevalence of 47.1% (95% CI 44-50). The most frequent error was omission of the prescribed medication. Intensive care unit stay was a risk factor associated with omission error (OR 2.14; 1.46-3.14: p .01). A total of 294 administration errors were identified for 249 drugs in 52 patients (mean error 6 [SD 6.7] per patient) and prevalence of 73.5% (95% CI 68-79). The most frequent error was interruption during drug administration. Admission to the intensive care unit (OR 0.37; 0.21-0.66: p .01), nurses' morning shift (OR 2.15; 1.10-4.18: p = .02) and workload perception (OR 3.64; 2.09-6.35: p .01) were risk factors associated with interruption.Medication errors in prescription and administration were frequent. Timely detection of errors and promotion of a medication safety culture are necessary to reduce them and ensure the quality of care in critically ill patients.Medication errors occur frequently in the intensive care unit but are not always identified. Due to the vulnerability of seriously ill patients and the specialized care they require, an error can result in serious adverse events. The study shows that medication errors in prescription and administration are recurrent but preventable. These findings contribute to promote awareness in the proper use of medications and guarantee the quality of nursing care.目的: 确定用药失误的发生率、程度及其与患者社会人口学、临床特征以及护士工作条件之间的关系。 设计: 对成年危重患者进行观察性、分析性、横向和双向性研究。 方法: 从病历中回顾性收集处方错误相关数据,并通过对护士在用药期间的直接观察,发现用药失误。此类数据于2015年4月至7月期间收集。 结果: 在90例患者使用的961种药物中共发现有650个处方错误(平均错误率7【SD 4.1】),发生率为47.1%(95%CI 44-50)。最为常见的一类错误是漏开处方药。重症监护病房住院时间是导致出现漏开失误的一大相关风险因素(OR2.14;1.46-3.14:p.01)。52例患者使用的249种药物中共发现有294个用药失误(平均失误率为6【SD 6.7】),发生率为73.5%(95%CI 68-79)。最为常见的一类失误是用药期间出现中断。入住重症监护病房(OR0.37;0.21-0.66:p.01)、护士早班交接(OR2.15;1.10-4.18:p= .02)以及工作负荷感知(OR3.64;2.09-6.35:p.01)为导致用药中断的相关风险因素。 结论: 处方用药错误频发。及时发现错误并倡导药物安全知识,对减少错误、保证危重患者护理质量具有重要意义。 影响: 在重症监护病房,药物错误经常发生,但并非总是得以发现。由于重病患者身体脆弱,且需特殊护理,此类错误可能导致严重的不良事件。研究表明,处方用药错误虽频频发生,但可予以预防。此等发现有助于提高人们对正确使用药物的认识,保证护理质量。.

Background The Pediatric Quality of Life Inventory™ (PedsQL™) Oral Health Scale was developed to measure oral health-related quality of life (OHRQoL). The aim of this study was to cross-culturally adapt the parent-reported version for toddlers of PedsQL™ Oral Health Scale into Spanish and to assess the acceptability, reliability and validity of this version in Chilean preschool population. Methods The PedsQL™ Oral Health Scale for toddlers was cross-culturally adapted for the Spanish language using the recommended standards. To assess metric properties, a cross-sectional study was carried out with 301 children aged 2 to 5 years in Carahue, Chile. Chilean versions of the PedsQL™ Oral Health Scale, PedsQL™ 4.0 Generic Core Scales, and Early Childhood Oral Health Impact Scale (ECOHIS) were completed by the children’s parents. Dental caries, malocclusion and dental trauma were examined by trained dentists. The PedsQL™ Oral Health Scale was administrated a second time 14–21 days after. The reliability of the scale was verified by analysis of internal consistency (Cronbach’s alpha) and reproducibility (Intraclass correlation coefficient – ICC). The validity of the construct was assessed by confirmatory factor analysis and known groups method. The convergent validity was assessed by calculating the Spearman’s correlation with the ECOHIS questionnaire. Results The PedsQL™ Oral Health Scale demonstrated good reliability, with Cronbach’s alpha coefficient of 0.79 and ICC of 0.85. A moderate-to-strong correlation was found between the PedsQL™ Oral Health Scale and the ECOHIS questionnaire (− 0.64); the PedsQL™ Oral Health Scale score was lower in children with poor than those with excellent/very good oral health (median 100 vs 85, p p Conclusions The PedsQL™ Oral Health Scale for toddlers in Spanish showed to be equivalent to the original version, and its psychometric properties were satisfactory for application in a Chilean pre-school population.

Hemostasis is crucial for reducing bleeding during surgical procedures. The points-of-care based on the platelet function test could be useful to minimize the complications related to chronic antiplatelet therapy during surgery. The present study is aimed at comparing two point-of-care platelet function devices&mdash, Platelet Function Analyzer PFA-100&reg, (Siemens Canada, Mississauga, ON, Canada) and Plateletworks&reg, (Helena Laboratories, Beaumont, TX, USA). Our objective is to evaluate if they provide comparable and useful information to manage anti-aggregate patients before surgery. We included patients with a femoral fracture receiving chronic antiplatelet therapy and a median age of 89 years (range from 70 to 98). A platelet function evaluation was performed on all patients before surgery using both devices&mdash, Plateletworks&reg, and PFA-100&reg, The correlation between Plateletworks&reg, was performed using Cohen&rsquo, s Kappa coefficient. Twenty consecutive patients participated in the trial, 16 patients were under treatment with 75 mg/day of clopidogrel, three with &gt, 300 mg/day of acetylsalicylic acid (ASA), and only one was in treatment with both antiplatelet agents. Cohen&rsquo, s Kappa coefficient was 0.327 comparing PFA-100&reg, ADP (adenosine diphosphate) and Plateletworks&reg, and, 0.200 comparing PFA-100&reg, EPI (epinephrine) and Plateletworks&reg, In conclusion, we found a weak concordance comparing PFA-100&reg, and Plateletworks&reg, This could partially be due to the advanced age of the included patients. However, given the limited sample size, more studies are necessary to confirm these results.

Background. Leukocytes contained in the allogeneic packed red blood cell (PRBC) are the cause of certain adverse reactions associated with blood transfusion. Leukoreduction consists of eliminating leukocytes in all blood products below the established safety levels for any patient type. In this systematic review, we appraise the clinical effectiveness of allogeneic leukodepleted (LD) PRBC transfusion for preventing infections and death in patients undergoing major cardiovascular surgical procedures.Methods. We searched randomized controlled trials (RCT), enrolling patients undergoing a major cardiovascular surgical procedure and transfused with LD-PRBC. Data were extracted, and risk of bias was assessed according to Cochrane guidelines. In addition, trial sequential analysis (TSA) was used to assess the need of conducting additional trials. Quality of the evidence was assessed using the GRADE approach.Results. Seven studies met the eligibility criteria. Quality of the evidence was rated as moderate for both outcomes. The risk ratio for death from any cause comparing the LD-PRBC versus non-LD-PRBC group was 0.69 (CI 95% = 0.53 to 0.90;I2 = 0%). The risk ratio for infection in the same comparison groups was 0.77 (CI 95% = 0.66 to 0.91;I2 = 0%). TSA showed a conclusive result in this outcome.Conclusions. We found evidence that supports the routine use of leukodepletion in patients undergoing a major cardiovascular surgical procedure requiring PRBC transfusion to prevent death and infection. In the case of infection, the evidence should be considered sufficient and conclusive and hence indicated that further trials would not be required.

We assessed the efficacy of fibrin sealant (FS) and tranexamic acid (TXA) administered topically in patients with a hip fracture treated with prosthetic replacement. Parallel, multicentre, open label, randomised, clinical trial. We compared three interventions to reduce blood loss: (1) 10 ml of FS, (2) 1 g of topical TXA, both administered at the end of the surgery, and (3) usual haemostasis (control group). The main outcome was blood loss collected in drains. Other secondary variables were total blood loss, hidden blood loss, transfusion rate, average hospital stay, complications, adverse events, and mortality. A total of 158 patients were included, 56 in the FS group, 52 in the TXA group, and 50 in the control group. The total amount of blood collected in drains was lower in the TXA group (148.6 ml, SD 122.7 in TXA; 168.2 ml, SD 137.4 in FS; and 201.5 ml, SD 166.5 in control group) without achieving statistical significance (p = 0.178). The transfusion rate was lower in the TXA group (32.7%), compared with FS group (42.9%) and control group (44.0%), without statistical significance (p = 0.341). There were no complications or adverse effects related to the evaluated interventions. The use of TXA and FS administered topically prior to surgical closure in patients with a sub-capital femoral fracture undergoing arthroplasty did not significantly reduce either postoperative blood loss or transfusion rate, compared with a group that only received usual haemostasis.

Objectives: Early childhood caries (ECC) constitutes a serious public health issue, especially in communities without water fluoridation. We assessed the effectiveness of biannual fluoride varnish applications to prevent ECC in children from nonfluoridated rural areas. Methods: A triple-blind randomized control trial with two parallel arms was conducted with 275 two-to three-year-old children without cavitated carious lesions from 28 rural public preschools in Chile. The preschools were located in areas of low socioeconomic status without access to fluoridated water. An oral health education component was administered to children, parents and educators. A new toothbrush and toothpaste for each child was delivered to the parents at baseline and at four follow-up visits. The participants were randomly allocated to receive fluoride varnish or placebo applications every six months. Trained, calibrated dentists blind to the treatment arm performed visual dental assessments at 6, 12, 18 and 24 months. The primary endpoint was the development of cavitated carious lesions in children during the 24-month follow-up period using WHO criteria, and the secondary outcomes were an increase in caries measured as a change in the index of decayed, missing or filled teeth (dmft) since the beginning of the study and the development of adverse effects. An intention-to-treat (ITT) approach was used for the primary analysis. Results: We included 131 participants in the intervention group and 144 participants in the placebo group; of these children, 89 (67.9%) in the intervention group and 100 (69.4%) in the control group completed the protocol. The comparative ITT analysis of caries incidence after 24 months of follow-up showed a between-group prevention fraction of 18.9% (-2.9%-36.2%). Caries incidence was 45.0% for the experiment group and 55.6% for the control group (P = .081), with a mean dmft of 1.6 (SD = 2.4) and 2.1 (SD = 2.5), respectively. No adverse effects were reported. Conclusions: In conclusion, biannual fluoride varnish application is not effective in preschool children from rural nonfluoridated communities at a high risk of caries.

OBJECTIVES: To obtain a systematic and standardized evaluation of the current evidence on development process, metric properties, and administration issues of oral health-related quality of life instruments available for children and adolescents. MATERIALS AND METHODS: A systematic search until October 2016 was conducted in PubMed, Embase, Lilacs, SciELO, and Cochrane databases. Articles with information regarding the development process, metric properties, and administration issues of pediatric instruments measuring oral health-related quality of life were eligible for inclusion. Two researchers independently evaluated each instrument applying the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. An overall and seven attribute-specific EMPRO scores were calculated (range 0-100, worst to best): measurement model, reliability, validity, responsiveness, interpretability, burden, and alternative forms. RESULTS: We identified 18 instruments evaluated in 132 articles. From five instruments designed for preschoolers, the Early Childhood Oral Health Impact Scale (ECOHIS) obtained the highest overall EMPRO score (82.2). Of nine identified for schoolchildren and adolescents, the best rated instrument was the Child Perceptions Questionnaire 11-14 (82.1). Among the four instruments developed for any age, the Family Impact Scale (FIS) obtained the highest scores (80.3). CONCLUSION: The evidence supports the use of the ECOHIS for preschoolers, while the age is a key factor when choosing among the four recommended instruments for schoolchildren and adolescents. Instruments for specific conditions, symptoms, or treatments need further research on metric properties. CLINICAL RELEVANCE: Our results facilitate decision-making on the correct oral health-related quality of life instrument selection for any certain study purpose and population during the childhood and adolescence life cycle.

Background Traumatic brain injury (TBI) is a major public health problem and a fundamental cause of morbidity and mortality worldwide. The burden of TBI disproportionately affects low-and middle-income countries. Intracranial hypertension is the most frequent cause of death and disability in brain-injured people. Special interventions in the intensive care unit are required to minimise factors contributing to secondary brain injury after trauma. Therapeutic positioning of the head (different degrees of head-of-bed elevation (HBE)) has been proposed as a low cost and simple way of preventing secondary brain injury in these people. The aim of this review is to evaluate the evidence related to the clinical effects of different backrest positions of the head on important clinical outcomes or, if unavailable, relevant surrogate outcomes. Objectives To assess the clinical and physiological effects of HBE during intensive care management in people with severe TBI. Search methods We searched the following electronic databases from their inception up to March 2017: Cochrane Injuries' Specialised Register, CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers. The Cochrane Injuries' Information Specialist ran the searches. Selection criteria We selected all randomised controlled trials (RCTs) involving people with TBI who underwent different HBE or backrest positions. Studies may have had a parallel or cross-over design. We included adults and children over two years of age with severe TBI (Glasgow Coma Scale (GCS) less than 9). We excluded studies performed in children of less than two years of age because of their unfused skulls. We included any therapeutic HBE including supine (flat) or different degrees of head elevation with or without knee gatch or reverse Trendelenburg applied during the acute management of the TBI. Data collection and analysis Two review authors independently checked all titles and abstracts, excluding references that clearly didn't meet all selection criteria, and extracted data from selected studies on to a data extraction form specifically designed for this review. There were no cases of multiple reporting. Each review author independently evaluated risk of bias through assessing sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias. Main results We included three small studies with a cross-over design, involving a total of 20 participants (11 adults and 9 children), in this review. Our primary outcome was mortality, and there was one death by the time of follow-up 28 days after hospital admission. The trials did not measure the clinical secondary outcomes of quality of life, GCS, and disability. The included studies provided information only for the secondary outcomes intracranial pressure (ICP), cerebral perfusion pressure (CPP), and adverse effects. We were unable to pool the results as the data were either presented in different formats or no numerical data were provided. We included narrative interpretations of the available data. The overall risk of bias of the studies was unclear due to poor reporting of the methods. There was marked inconsistency across studies for the outcome of ICP and small sample sizes or wide confidence intervals for all outcomes. We therefore rated the quality of the evidence as very low for all outcomes and have not included the results of individual studies here. We do not have enough evidence to draw conclusions about the effect of HBE during intensive care management of people with TBI. Authors' conclusions The lack of consistency among studies, scarcity of data and the absence of evidence to show a correlation between physiological measurements such as ICP, CCP and clinical outcomes, mean that we are uncertain about the effects of HBE during intensive care management in people with severe TBI. Well-designed and larger trials that measure long-term clinical outcomes are needed to understand how and when different backrest positions can affect the management of severe TBI.

ObjectivesTo evaluate the quality of clinical practice guidelines (CPGs) for dental caries prevention in children and adolescentsMaterials and methodsWe performed a systematic search of CPGs on caries preventive measures between 2005 and 2016. We searched MEDLINE, EMBASE, LILACS, TripDatabase, websites of CPG developers, compilers of CPGs, scientific societies and ministries of health. We included CPGs with recommendations on sealants, fluorides and oral hygiene. Three reviewers independently assessed the included CPGs using the AGREE II instrument. We calculated the standardised scores for the six domains and made a final recommendation about each CPG. Also, we calculated the overall agreement among calibrated reviewers with the intraclass correlation coefficient (ICC).ResultsTwenty-two CPGs published were selected from a total of 637 references. Thirteen were in English and nine in Spanish. The overall agreement between reviewers was very good (ICC=0.90; 95%CI 0.89-0.92). The mean score for each domain was the following: Scope and purpose 89.612%; Stakeholder involvement 55.015.6%; Rigour of development 64.9 +/- 21.2%; Clarity of presentation 84.8 +/- 14.1%; Applicability 30.6 +/- 31.5% and Editorial independence 59.3 +/- 25.5%. Thirteen CPGs (59.1%) were assessed as recommended, eight (36.4%) recommended with modifications and one (4.5%) not recommended.Conclusions The overall quality of CPGs in caries prevention was moderate. The domains with greater deficiencies were Applicability, Stakeholder involvement and Editorial independence.Clinical relevance Clinicians should use the best available CPGs in dental caries prevention to provide optimal oral health care to patients.

BACKGROUND The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8 ºC). Whilst the common cold is generally not harmful, it is a cause of economic burden due to school and work absenteeism. In the United States, economic loss due to the common cold is estimated at more than USD 40 billion per year, including an estimate of 70 million workdays missed by employees, 189 million school days missed by children, and 126 million workdays missed by parents caring for children with a cold. Additionally, data from Europe show that the total cost per episode may be up to EUR 1102. There is also a large expenditure due to inappropriate antimicrobial prescription. Vaccine development for the common cold has been difficult due to antigenic variability of the common cold viruses; even bacteria can act as infective agents. Uncertainty remains regarding the efficacy and safety of interventions for preventing the common cold in healthy people, thus we performed an update of this Cochrane Review, which was first published in 2011 and updated in 2013 and 2017. OBJECTIVES To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (April 2022), MEDLINE (1948 to April 2022), Embase (1974 to April 2022), CINAHL (1981 to April 2022), and LILACS (1982 to April 2022). We also searched three trials registers for ongoing studies, and four websites for additional trials (April 2022). We did not impose any language or date restrictions. SELECTION CRITERIA Randomised controlled trials (RCTs) of any virus vaccine compared with placebo to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS We used Cochrane's Screen4Me workflow to assess the initial search results. Four review authors independently performed title and abstract screening to identify potentially relevant studies. We retrieved the full-text articles for those studies deemed potentially relevant, and the review authors independently screened the full-text reports for inclusion in the review, recording reasons for exclusion of the excluded studies. Any disagreements were resolved by discussion or by consulting a third review author when needed. Two review authors independently collected data on a data extraction form, resolving any disagreements by consensus or by involving a third review author. We double-checked data transferred into Review Manager 5 software. Three review authors independently assessed risk of bias using RoB 1 tool as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We carried out statistical analysis using Review Manager 5. We did not conduct a meta-analysis, and we did not assess publication bias. We used GRADEpro GDT software to assess the certainty of the evidence and to create a summary of findings table. MAIN RESULTS: We did not identify any new RCTs for inclusion in this update. This review includes one RCT conducted in 1965 with an overall high risk of bias. The RCT included 2307 healthy young men in a military facility, all of whom were included in the analyses, and compared the effect of three adenovirus vaccines (live, inactivated type 4, and inactivated type 4 and 7) against a placebo (injection of physiological saline or gelatin capsule). There were 13 (1.14%) events in 1139 participants in the vaccine group, and 14 (1.19%) events in 1168 participants in the placebo group. Overall, we do not know if there is a difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; very low-certainty evidence). Furthermore, no difference in adverse events when comparing live vaccine preparation with placebo was reported. We downgraded the certainty of the evidence to very low due to unclear risk of bias, indirectness because the population of this study was only young men, and imprecision because confidence intervals were wide and the number of events was low. The included study did not assess vaccine-related or all-cause mortality. AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with very low-certainty evidence, which showed that there may be no difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold. We identified a need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Future trials on interventions for preventing the common cold should assess a variety of virus vaccines for this condition, and should measure such outcomes as common cold incidence, vaccine safety, and mortality (all-cause and related to the vaccine).

BACKGROUND: This is an update of the review published in Issue 4, 2003. Bone metastasis cause severe pain as well as pathological fractures, hypercalcaemia and spinal cord compression. Treatment strategies currently available to relieve pain from bone metastases include analgesia, radiotherapy, surgery, chemotherapy, hormone therapy, radioisotopes and bisphosphonates. OBJECTIVES: To determine efficacy and safety of radioisotopes in patients with bone metastases to improve metastatic pain, decrease number of complications due to bone metastases and improve patient survival. SEARCH METHODS: We sought randomised controlled trials (RCTs) in MEDLINE, EMBASE, CENTRAL, and the PaPaS Trials Register up to October 2010. SELECTION CRITERIA: Studies selected had metastatic bone pain as a major outcome after treatment with a radioisotope, compared with placebo or another radioisotope. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of included studies by their sequence generation, allocation concealment, blinding of study participants, researchers and outcome assessors, and incomplete outcome data. Two review authors extracted data. We performed statistical analysis as an "available case" analysis, and calculated global estimates of effect using a random‐effects model. We also performed an intention‐to‐treat (ITT) sensitivity analysis. MAIN RESULTS: This update includes 15 studies (1146 analyzed participants): four (325 participants) already included and 11 new (821 participants). Only three studies had a low risk of bias. We observed a small benefit of radioisotopes for complete relief (risk ratio (RR) 2.10, 95% CI 1.32 to 3.35; Number needed to treat to benefit (NNT) = 5) and complete/partial relief (RR 1.72, 95% CI 1.13 to 2.63; NNT = 4) in the short and medium term (eight studies, 499 participants). There is no conclusive evidence to demonstrate that radioisotopes modify the use of analgesia with respect to placebo. Leucocytopenia and thrombocytopenia are secondary effects significantly associated with the administration of radioisotopes (RR 5.03; 95% CI 1.35 to 18.70; Number needed to treat to harm (NNH) = 13). Pain flares were not higher in the radioisotopes group (RR 0.74; 95% CI 0.27 to 2.06). There are scarce data of moderate quality when comparing Strontium‐89 ((89)Sr) with Samarium‐153 ((153)Sm), Rhenium‐186 ((186)Re) and Phosphorus‐32 ((32)P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of (153)Sm (0.5 versus 1.0 mCi). AUTHORS' CONCLUSIONS: This update adds new evidence on efficacy of radioisotopes versus placebo, (89)Sr compared with other radioisotopes, and dose‐comparisons of (153)Sm and (188)Re. There is some evidence indicating that radioisotopes may provide complete reduction in pain over one to six months with no increase in analgesic use, but severe adverse effects (leucocytopenia and thrombocytopenia) are frequent.

Resumen El sangrado perioperatorio en ocasiones conduce a transfusiones sanguineas no exentas de complicaciones y riesgos, con un alto gasto sanitario. Entre otros metodos de prevencion, el tratamiento con acido tranexamico (TXA) ha mostrado ser efectivo en la disminucion de las perdidas sanguineas quirurgicas y especialmente en el postoperatorio inmediato. Al respecto, los estudios que lo han evaluado en cirugia ortopedica muestran su eficacia y seguridad, administrado por via tanto intravenosa como intraarticular. Las dosis habituales por via intravenosa evaluadas oscilan entre 10 y 20 mg/kg, o en dosis fijas de 1 a 2 g, mientras por via intraarticular varia entre 250 mg y 3 g. El TXA como antifibrinolitico tiene un potencial efecto trombotico y esta contraindicado en aquellos pacientes con riesgo o antecedentes de trombosis. Su administracion por via topica podria ser mas segura aunque se precisan estudios que lo confirmen.

Background: Postoperative blood loss in patients after total knee arthroplasty may cause local and systemic complications and influence clinical outcome. The aim of this study was to assess whether fibrin glue or tranexamic acid reduced blood loss compared with routine hemostasis in patients undergoing total knee arthroplasty. Methods: A randomized, single-center, parallel, open clinical trial was performed in adult patients undergoing primary total knee arthroplasty. Patients were divided into four groups. Group 1 received fibrin glue manufactured by the Blood and Tissue Bank of Catalonia, Group 2 received Tissucol (fibrinogen and thrombin), Group 3 received intravenous tranexamic acid, and Group 4 (control) had no treatment other than routine hemostasis. The primary outcome was total blood loss collected in drains after surgery. Secondary outcomes were the calculated hidden blood loss, transfusion rate, preoperative and postoperative hemoglobin, number of blood units transfused, adverse events, and mortality. Results: One hundred and seventy-two patients were included. The mean total blood loss (and standard deviation) collected in drains was 553.9 ± 321.5 mL for Group 1, 567.8 ± 299.3 mL for Group 2, 244.1 ± 223.4 mL for Group 3, and 563.5 ± 269.7 mL for Group 4. In comparison with the control group, Group 3 had significantly lower total blood loss (p < 0.001), but it was not significantly lower in Groups 1 and 2. The overall rate of patients who had a blood transfusion was 21.1% (thirty-five of 166 patients analyzed per protocol). Two patients required transfusion in Group 3 compared with twelve patients in Group 4 (p = 0.015). No significant difference was observed between the two fibrin glue groups and the control group with regard to the need for transfusion. There was no difference between groups with regard to the percentage of adverse events. Conclusions: Neither type of fibrin glue was more effective than routine hemostasis in reducing postoperative bleeding and transfusion requirements, and we no longer use them. However, this trial supports findings from previous studies showing that intravenous tranexamic acid can decrease postoperative blood loss. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The objective of this review is to assess the effectiveness of interval training on mortality, morbidity, and BP control in hypertensive individuals. We will also assess the effects on cardiovascular‐specific mortality, cardiovascular risk factor control, cardiorespiratory fitness, heart rate, health‐related quality of life, treatment adherence, and adverse events.

Objectives Traumatic dental injuries (TDIs) in childhood and adolescence are a potential public health problem given their prevalence and consequences. The aim of this study was to assess the impact of TDIs on the oral health-related quality of life (OHRQoL) of preschoolers and schoolchildren, by synthesizing the available evidence. Methods A systematic search was conducted in MEDLINE, EMBASE, Cochrane, ScieLo and Lilacs databases since January 1966 until March 2016. The included studies compared OHRQoL between groups with and without TDIs, using validated instruments. The selection process and data extraction were carried out by two researchers independently. A third reviewer resolved discrepancies. Methodological quality was assessed with the Effective Public Health Practice Project's Quality Assessment Tool. Meta-analyses were performed using random effect models, separately for preschoolers and schoolchildren. Results Of 213 identified articles, 26 studies (involving a total of 4582 patients and 13 601 controls between the ages of 1 and 15 years) met the inclusion criteria. Most of the studies had been published in the last 5 years, and their methodological quality was judged to be moderate. The TDIs group had a significantly higher chance of reporting any impact on OHRQoL than controls for both preschoolers (OR = 1.44; 95% confidence interval [CI]: 1.28-1.63; I2 = 0%) and schoolchildren (OR = 1.31; 95% CI: 1.04-1.66; I2 = 70%). In preschoolers, the OR for OHRQoL impact for complicated vs uncomplicated TDIs was 1.53 (95% CI: 1.04-2.26; I2 = 0%). The social domain was the most affected one in schoolchildren (standard mean difference = 0.34; 95% CI: 0.13, 0.55; I2 = 68%). Conclusion Traumatic dental injuries have a negative impact on OHRQoL of both preschoolers and schoolchildren. Outcome standardization to measure OHRQoL impact, such as mean score differences and cut-off points, is needed. Prospective cohort studies are recommended to confirm these findings and to understand how TDIs’ impact changes with time.

Altres ajuts: This study was partially funded by the 2014 Cochrane Collaboration Discretionary Fund. The remaining funding was provided by the Iberoamerican Cochrane Centre. The funding bodies did not have any role in the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication. This study was partially funded by the 2014 Cochrane Collaboration Discretionary Fund. The remaining funding was provided by the Iberoamerican Cochrane Centre. The funding bodies did not have any role in the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication. Systematic reviews provide the best evidence on the effect of health care interventions. They rely on comprehensive access to the available scientific literature. Electronic search strategies alone may not suffice, requiring the implementation of a handsearching approach. We have developed a database to provide an Internet-based platform from which handsearching activities can be coordinated, including a procedure to streamline the submission of these references into CENTRAL, the Cochrane Collaboration Central Register of Controlled Trials. We developed a database and a descriptive analysis. Through brainstorming and discussion among stakeholders involved in handsearching projects, we designed a database that met identified needs that had to be addressed in order to ensure the viability of handsearching activities. Three handsearching teams pilot tested the proposed database. Once the final version of the database was approved, we proceeded to train the staff involved in handsearching. The proposed database is called BADERI (Database of Iberoamerican Clinical Trials and Journals, by its initials in Spanish). BADERI was officially launched in October 2015, and it can be accessed at free of cost. BADERI has an administration subsection, from which the roles of users are managed; a references subsection, where information associated to identified controlled clinical trials (CCTs) can be entered; a reports subsection, from which reports can be generated to track and analyse the results of handsearching activities; and a built-in free text search engine. BADERI allows all references to be exported in ProCite files that can be directly uploaded into CENTRAL. To date, 6284 references to CCTs have been uploaded to BADERI and sent to CENTRAL. The identified CCTs were published in a total of 420 journals related to 46 medical specialties. The year of publication ranged between 1957 and 2016. BADERI allows the efficient management of handsearching activities across different countries and institutions. References to all CCTs available in BADERI can be readily submitted to CENTRAL for their potential inclusion in systematic reviews. The online version of this article (doi:10.1186/s13063-017-2023-3) contains supplementary material, which is available to authorized users.

Introduction Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS. Methods Serum samples from patients with MS (n = 108) and controls (n = 77) were tested for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with the low-glycosylated fraction of recombinant KIR4.1 purified from transfected HEK293 cells according to original protocols; 2) by immunocytochemistry using KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.-transfected MO3.13 oligodendrocyte cell line. We developed a systematic review and meta-analysis of the association of anti-KIR4.1 antibodies with MS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results We did not detect anti-KIR4.1 antibodies in the MS patients or in controls using ELISA. Neither did we detect any significant reactivity against the antigen on the cell surface using the KIR4.1-transfected HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective controlled studies in the systematic review. Only three studies showed a positive association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity between studies precluded meta-analysis of their results. Conclusion We found no association between anti-KIR4.1 antibody positivity and MS. Although this lack of replication may be due to technical limitations, evidence from our study and others is mounting against the role of KIR4.1 as a relevant MS autoantigen.

Objective We performed a cohort study in seven hospitals in Spain to determine the clinical characteristics of incident patients with bladder cancer, the diagnostic process, and the conditions that might affect health care interval times. Results 314 patients with bladder cancer were included, 70.3 (Standard Deviation [SD] 11.2) years old and 85.0% male. Clinical stage was T1 in 45.9% of patients. The median interval time between first consultation and diagnosis was of 104.0 days (Inter quartile range [IQR]:112.0; range from 0 to 986), being shorter for those patients who attended a hospital for their first consultation. The median interval time between diagnosis and first treatment was of 0.0 days (IQR: 0.0; range from 0 to 366), being longer when the patient had a pathologic tumor stage ≥ T2a. Electronic supplementary material The online version of this article (10.1186/s13104-017-3024-8) contains supplementary material, which is available to authorized users.

Purpose The aim of the present study was to determine the success rate of autotransplanted permanent teeth with an open apex and to identify the most influential prognostic factors. Materials and Methods A systematic search of the MEDLINE, EMBASE, LILACS, and SciELO databases was conducted for January 1990 to August 2015. The study eligibility criteria were primary studies that had evaluated patients with autotransplantation with an open apex, with or without preparation of the socket, and a minimum of 12 months of follow-up. The principal outcome was the success rate of autotransplanted teeth with an open apex. Two of us independently performed the selection process and data extraction. The Effective Public Health Practice Project's Quality Assessment Tool was used for the quality assessment of the studies. The odds ratio (OR) was calculated, with the 95% confidence interval (CI). Results A total of 21 studies were included in the present analysis. Of the 21 studies, 10 were retrospective and 11 were prospective. All the studies were of weak methodologic quality. The overall success rate was 89.68%, the survival rate was 98.21%, and the mean follow-up period was 6 years, 3 months (standard deviation 5.81 years). Among the prognostic factors analyzed, the premolars had a lower failure risk than did the molars (OR, 0.46; 95% CI, 0.25 to 0.84). The stage of development of the root and the autotransplantation receptor site showed no statistically significant differences. Conclusions The overall success rate and survival were high, despite the methodologic limitations of the included studies. Further study is needed of the prognostic factors that influence the success of autotransplantation with an open apex.

Objective The consumption of fruits and vegetables (FV) may contribute to the prevention of many diseases. However, children at school age do not eat an enough amount of those foods. We have systematically reviewed the literature to assess the effectiveness of school interventions for promoting the consumption of FV. Methods We performed a search in MEDLINE, EMBASE, CINAHL and CENTRAL. We pooled results and stratified the analysis according to type of intervention and study design. Results Nineteen cluster studies were included. Most studies did not describe randomization method and did not take the cluster's effect into account. Pooled results of two randomized controlled trials (RCTs) of computer-based interventions showed effectiveness in improving consumption of FV [Standardized Mean Difference (SMD) 0.33 (95% CI 0.16, 0.50)]. No significant differences were found in pooled analysis of seven RCTs of multicomponent interventions or pooling results of two RCTs evaluating free/subsidized FV interventions. Conclusions Meta-analysis shows that computer-based interventions were effective in increasing FV consumption. Multicomponent interventions and free/subsidized FV interventions were not effective. Improvements in methodology are needed in future cluster studies. Although these results are preliminary, computer-based interventions could be considered in schools, given that they are effective and cheaper than other alternatives.

Objective: There is increasing evidence to suggest that ossein-hydroxyapatite complex (OHC) is more effective than calcium supplements in maintaining bone mass. The aim of this meta-analysis was to determine whether OHC has a different clinical effect on bone mineral density (BMD) compared with calcium carbonate (CC). Methods: A meta-analysis of randomized controlled clinical trials was carried out to evaluate the efficacy of OHC versus CC on trabecular BMD. We identified publications on clinical trials by a search of electronic databases, including MEDLINE (1966-November 2008), EMBASE (1974-November 2008), and the Cochrane Controlled Clinical Trials Register. The primary endpoint was percent change in BMD from baseline. Data were pooled in a random-effects model, and the weighted mean difference was calculated. A sensitivity analysis that excluded trials without full data was performed. Results: Of the 18 controlled trials initially identified, 6 were included in the meta-analysis. There was no significant heterogeneity among the included trials. The percent change in BMD significantly favored the OHC group (1.02% [95% CI, 0.63-1.41], P < 0.00001). These results were confirmed in the sensitivity analysis. Conclusions: OHC is significantly more effective in preventing bone loss than CC.

Objective. To assess the efficacy of calcium dobesilate on the quality-of-life (QoL) of patients with chronic venous disease (CVD). Design. Randomised, parallel, double blind, placebo-controlled clinical trial. Methods. Patients were recruited from vascular surgery clinics and randomised to 500 mg capsules of calcium dobesilate twice a day for 3 months or placebo. The primary outcome measure was ‘QoL after 3 months’ treatment measured by the specific Chronic Insufficiency Venous International Questionnaire (CIVIQ). Secondary outcomes were QoL at 12 months and assessment of the CVD signs and symptoms. The principal analysis was undertaken on the intention-to-treat (ITT) data. Results. Five hundred and nine patients were recruited (246 to calcium dobesilate and 263 to placebo). The analysis of the ‘QoL after 3 months’ showed no significant differences between groups (p ¼0.07). For secondary outcomes, oedema and symptoms of CVD, there were no significant differences between groups. In a multi-factorial analysis, the ‘QoL at 12 months’ was better in the calcium dobesilate group than in placebo group (p ¼ 0.02). Conclusions. Treatment with calcium dobesilate was not found to be superior to placebo on the QoL of CVD patients. The sustained effect of calcium dobesilate observed after treatment should be confirmed in future studies. 2007 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

BACKGROUND: Many surgical approaches are available to treat varicose veins secondary to chronic venous insufficiency. One of the least invasive techniques is the ambulatory conservative hemodynamic correction of venous insufficiency method (in French 'cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire' (CHIVA)), an approach based on venous hemodynamics with deliberate preservation of the superficial venous system. This is the second update of the review first published in 2013. OBJECTIVES: To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, AMED, and the World Health Organisation International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 19 October 2020. We also searched PUBMED to 19 October 2020 and checked the references of relevant articles to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared CHIVA to other therapeutic techniques to treat varicose veins. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed and selected studies, extracted data, and performed quantitative analysis from the selected papers. A third author solved any disagreements. We assessed the risk of bias in included trials with the Cochrane risk of bias tool. We calculated the risk ratio (RR), mean difference (MD), number of people needed to treat for an additional beneficial outcome (NNTB), and the number of people needed to treat for an additional harmful outcome (NNTH), with 95% confidence intervals (CI). We evaluated the certainty of the evidence using GRADE. The main outcomes of interest were the recurrence of varicose veins and side effects. MAIN RESULTS: For this update, we identified two new additional studies. In total, we included six RCTs with 1160 participants (62% women) and collected from them eight comparisons. Three RCTs compared CHIVA with vein stripping. One RCT compared CHIVA with compression dressings in people with venous ulcers. The new studies included three comparisons, one compared CHIVA with vein stripping and radiofrequency ablation (RFA), and one compared CHIVA with vein stripping and endovenous laser therapy. We judged the certainty of the evidence for our outcomes as low to very low due to inconsistency, imprecision caused by the low number of events and risk of bias. The overall risk of bias across studies was high because neither participants nor personnel were blinded to the interventions. Two studies attempted to blind outcome assessors, but the characteristics of the surgery limited concealment. Five studies reported the outcome clinical recurrence of varicose veins with a follow‐up of 18 months to 10 years. CHIVA may make little or no difference to the recurrence of varicose veins in the lower limb compared to stripping (RR 0.74, 95% CI 0.46 to 1.20; 5 studies, 966 participants; low‐certainty evidence). We are uncertain whether CHIVA reduced recurrence compared to compression dressing (RR 0.23, 95% CI 0.06 to 0.96; 1 study, 47 participants; very low‐certainty evidence). CHIVA may make little or no difference to clinical recurrence compared to RFA (RR 2.02, 95% CI 0.74 to 5.53; 1 study, 146 participants; low‐certainty evidence) and endovenous laser (RR 0.20, 95% CI 0.01 to 4.06; 1 study, 100 participants; low‐certainty evidence). We found no clear difference between CHIVA and stripping for the side effects of limb infection (RR 0.83, 95% CI 0.33 to 2.10; 3 studies, 746 participants; low‐certainty evidence), and superficial vein thrombosis (RR 1.05, 95% CI 0.51 to 2.17; 4 studies, 846 participants; low‐certainty evidence). CHIVA may reduce slightly nerve injury (RR 0.14, 95% CI 0.02 to 0.98; NNTH 9, 95% CI 5 to 100; 4 studies, 846 participants; low‐certainty evidence) and hematoma compared to stripping (RR 0.59, 95% CI 0.37 to 0.97; NNTH 11, 95% CI 5 to 100; 2 studies, 245 participants; low‐certainty evidence). For bruising, one study found no differences between groups while another study found reduced rates of bruising in the CHIVA group compared to the stripping group. Compared to RFA, CHIVA may make little or no difference to rates of limb infection, superficial vein thrombosis, nerve injury or hematoma, but may cause more bruising (RR 1.15, 95% CI 1.04 to 1.28; NNTH 8, CI 95% 5 to 25; 1 study, 144 participants; low‐certainty evidence). Compared to endovenous laser, CHIVA may make little or no difference to rates of limb infection, superficial vein thrombosis, nerve injury or hematoma. The study comparing CHIVA versus compression did not report side effects. AUTHORS' CONCLUSIONS: There may be little or no difference in the recurrence of varicose veins when comparing CHIVA to stripping (low‐certainty evidence), but CHIVA may slightly reduce nerve injury and hematoma in the lower limb (low‐certainty evidence). Very limited evidence means we are uncertain of any differences in recurrence when comparing CHIVA with compression (very low‐certainty evidence). CHIVA may make little or no difference to recurrence compared to RFA (low‐certainty evidence), but may result in more bruising (low‐certainty evidence). CHIVA may make little or no difference to recurrence and side effects compared to endovenous laser therapy (low‐certainty evidence). However, we based these conclusions on a small number of trials with a high risk of bias as the effects of surgery could not be concealed, and the results were imprecise due to the low number of events. New RCTs are needed to confirm these results and to compare CHIVA with approaches other than open surgery.

Background The aim of the study was to evaluate the impact of flavonoids on those symptoms important to patients with symptomatic haemorrhoids. Methods A comprehensive search strategy was used. All published and unpublished randomized controlled trials comparing any type of flavonoid to placebo or no therapy in patients with symptomatic haemorrhoids were included. Two reviewers independently screened studies for inclusion, retrieved all potentially relevant studies and extracted data. Results Fourteen eligible trials randomized 1514 patients. Studies were of moderate quality and showed variability in the results with potential publication bias. Meta-analyses using random-effects models suggested that flavonoids decrease the risk of not improving or persisting symptoms by 58 per cent (relative risk (RR) 0·42 (95 per cent confidence interval (c.i.) 0·28 to 0·61)) and showed an apparent reduction in the risk of bleeding (RR 0·33 (95 per cent c.i. 0·19 to 0·57)), persistent pain (RR 0·35 (95 per cent c.i. 0·18 to 0·69)), itching (RR 0·65 (95 per cent c.i. 0·44 to 0·97)) and recurrence (RR 0·53 (95 per cent c.i. 0·41 to 0·69)). Conclusion Limitations in methodological quality, heterogeneity and potential publication bias raise questions about the apparent beneficial effects of flavonoids in the treatment of haemorrhoids.

NTRODUCTION: Tranexamic acid (TXA) is becoming widely used in orthopedic surgery to reduce blood loss and transfusion requirements, but consensus is lacking regarding the optimal route and dose of administration. The aim of this study was to compare the efficacy and safety of topical and intravenous routes of TXA with routine hemostasis in patients undergoing primary total knee arthroplasty (TKA). MATERIALS AND METHODS: We performed a randomized, multicenter, parallel, open-label clinical trial in adult patients undergoing primary TKA. Patients were divided into three groups of 50 patients each: Group 1 received 1 g topical TXA, Group 2 received 2 g intravenous TXA, and Group 3 (control group) had routine hemostasis. The primary outcome was total blood loss. Secondary outcomes were hidden blood loss, blood collected in drains, transfusion rate, number of blood units transfused, adverse events, and mortality. RESULTS: One hundred and fifty patients were included. Total blood loss was 1021.57 (481.09) mL in Group 1, 817.54 (324.82) mL in Group 2 and 1415.72 (595.11) mL in Group 3 (control group). Differences in total blood loss between the TXA groups and the control group were clinically and statistically significant (p < 0.001). In an exploratory analysis differences between the two TXA groups were not statistically significant (p = 0.073) Seventeen patients were transfused. Transfusion requirements were significantly higher in Group 3 (p = 0.005). No significant differences were found between groups regarding adverse events. CONCLUSION:/nWe found that 1 g of topical TXA and 2 g of intravenous TXA were both safe strategies and more effective than routine hemostasis to reduce blood loss and transfusion requirements after primary TKA. This project was funded principally by a grant from the Spanish Ministry of Health and Social Policy to promote independent clinical research 2010 (EC10-73).

Background The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. Objectives To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014. Selection criteria Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. Data collection and analysis Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. Main results Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl (R) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. Authors' conclusions There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports. We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses. This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

Background Proliferative diabetic retinopathy (PDR) is a complication of diabetic retinopathy that can cause blindness. Although panretinal photocoagulation (PRP) is the treatment of choice for PDR, it has secondary effects that can affect vision. An alternative treatment such as anti-vascular endothelial growth factor (anti-VEGF), which produces an inhibition of vascular proliferation, could improve the vision of people with PDR. Objectives To assess the effectiveness and safety of anti-VEGFs for PDR. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to April 2014), EMBASE (January 1980 to April 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 April 2014. Selection criteria We included randomised controlled trials (RCTs) comparing anti-VEGFs to another active treatment, sham treatment or no treatment for people with PDR. We also included studies that assessed the combination of anti-VEGFs with other treatments. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and assessed risk of bias for all included trials. We calculated the risk ratio (RR) or the mean difference (MD), and 95% confidence intervals (CI). Main results We included 18 RCTs with 1005 participants (1131 eyes) of whom 57% were men. The median number of participants per RCT was 40 (range 15 to 261). The studies took place in Asia (three studies), Europe (two studies), the Middle East (seven studies), North America (three studies) and South America (three studies). Eight RCTs recruited people eligible for PRP, nine RCTs enrolled people with diabetes requiring vitrectomy and one RCT recruited people undergoing cataract surgery. The median follow-up was six months (range one to 12 months). Seven studies were at high risk of bias and the remainder were unclear risk of bias in one or more domains. Very low quality evidence from one study of 61 people showed that people treated with bevacizumab and PRP were less likely to lose 3 or more lines of visual acuity at 12 months compared with people treated with PRP alone (RR 0.19, 95% CI 0.05 to 0.81). People treated with anti-VEGF had an increased chance of gaining 3 or more lines of visual acuity but the effect was imprecise and compatible with no effect or being less likely to gain vision (RR 6.78, 95% CI 0.37 to 125.95). No other study reported these two outcomes. On average, people treated with anti-VEGF (bevacizumab, pegaptanib or ranibizumab) had better visual acuity at 12 months compared with people not receiving anti-VEGF (MD -0.07 logMAR, 95% CI -0.12 to -0.02; 5 RCTs, 373 participants, low quality evidence). There was some evidence to suggest a regression of PDR with smaller leakage on fluorescein angiography but it was difficult to estimate a pooled result from the two trials reporting this outcome. People receiving anti-VEGF were less likely to have vitreous or pre-retinal haemorrhage at 12 months (RR 0.32, 95% CI 0.16 to 0.65; 3 RCTs, 342 participants, low quality evidence). No study reported on fluorescein leakage or quality of life. All of the nine trials of anti-VEGF before or during vitrectomy investigated bevacizumab; most studies investigated bevacizumab before vitrectomy, one study investigated bevacizumab during surgery. People treated with bevacizumab and vitrectomy were less likely to lose 3 or more lines of visual acuity at 12 months compared with people given vitrectomy alone but the effect was imprecise and compatible with no effect or being more likely to lose vision (RR 0.49, 95% CI 0.08 to 3.14; 3 RCTs, 94 participants, low quality evidence). People treated with bevacizumab were more likely to gain 3 or more lines of visual acuity (RR 1.62, 95% CI 1.20 to 2.17; 3 RCTs, 94 participants, low quality evidence). On average, people treated with bevacizumab had better visual acuity at 12 months compared with people not receiving bevacizumab but there was uncertainty in the estimate (the CIs included 0; i.e. were compatible with no effect, and there was considerable inconsistency between studies; MD -0.24 logMAR, 95% CI -0.50 to 0.01; 6 RCTs, 335 participants, I2 = 67%; low quality evidence). People receiving bevacizumab were less likely to have vitreous or pre-retinal haemorrhage at 12 months (RR 0.30, 95% CI 0.18 to 0.52; 7 RCTs, 393 participants, low quality evidence). No study reported on quality of life. Reasons for downgrading the quality of the evidence included risk of bias in included studies, imprecision of the estimates, inconsistency of effect estimates and indirectness (few studies reported at 12 months). Adverse effects were rarely reported and there was no evidence for any increased risk with anti-VEGF but given the relatively few studies that reported these, and the low event rate, the power of the analysis to detect any differences was low. Authors' conclusions There was very low or low quality evidence from RCTs for the efficacy and safety of anti-VEGF agents when used to treat PDR over and above current standard treatments. However, the results suggest that anti-VEGFs can reduce the risk of intraocular bleeding in people with PDR. Further carefully designed clinical trials should be able to improve this evidence.

Background Low fruit and vegetable (FV) consumption is one of the top 10 global risk factors for mortality, and is related to increased risk for cancer, cardiovascular disease and diabetes. Many environmental, sociodemographic and personal factors affect FV consumption. The purpose of this review is to examine the effects of interventions delivered in the home, school and other nutritional environments designed to increase FV availability for five to 18-year olds. Methods The search included: 19 electronic bibliographic databases; grey literature databases; reference lists of key articles; targeted Internet searching of key organization websites; hand searching of key journals and conference proceedings; and consultation with experts for additional references. Articles were included if: in English, French and Spanish; from high-, middle-, and low-income countries; delivered to anyone who could bring about change in FV environment for 5 to 18 year olds; with randomized and non-randomized study designs that provided before-after comparisons, with or without a control group. Primary outcomes of interest were measures of FV availability. Results The search strategy retrieved nearly 23,000 citations and resulted in 23 unique studies. Interventions were primarily policy interventions at the regional or state level, a number of curriculum type interventions in schools and community groups and a garden intervention. The majority of studies were done in high-income countries. The diversity of interventions, populations, outcomes and outcome measurements precluded meta-analysis. The most promising strategies for improving the FV environment for children are through local school food service policies. Access to FV was successfully improved in four of the six studies that evaluated school-based policies, with the other two studies finding no effect. Broader state or federally mandated policies or educational programs for food service providers and decision makers had mixed or small impact. Similarly family interventions had no or small impact on home accessibility, with smaller impact on consumption. Conclusions The studies have high risk of bias but more rigorous studies are difficult to impossible to conduct in naturalistic settings and in policy implementation and evaluation. However, there are promising strategies to improve the FV environment, particularly through school food service policies.

Few studies describe the effect of non-muscle-invasive bladder cancer (NMIBC) on health-related quality of life (HRQL), although patients are mostly diagnosed at this stage of the disease. Taking into account this current evidence gap and the high incidence rates in Spain, we aimed to describe the evolution over time of HRQL in Spanish patients with NMIBC and to examine the clinical and treatment-related factors associated with HRQL change during the first year of management.Observational multicenter prospective inception cohort study conducted in urology departments of 7 Spanish hospitals. A consecutive sample of 244 patients with anatomopathologically confirmed NMIBC, recruited from October 2010 to September 2011, was followed during the diagnostic process, and 6 and 12 months later. HRQL was assessed by generic and disease-specific instruments: the Short Form-36 (covering physical and mental health) and the Bladder Cancer Index, measuring urinary, bowel, and sexual domains (summary scores: 0-100). Bivariate analysis was performed and generalized estimating equation models were constructed to assess HRQL score change.Almost 52% of the patients were diagnosed at stage I, and 84% were men. The number of patients treated only with transurethral resection (TUR) was 144, and 82 also received intravesical therapy with bacillus Calmette-Guérin (BCG) or mitomycin C. Mental health was significantly worse than Short Form-36 reference norms at diagnosis (mean of 49.7 vs. 53.3, 95% CI: 52.5-54.2). Urinary domain improved significantly from diagnosis (85.2, 95% CI: 82.9-87.4) to 12-month evaluation (90.2, 95% CI: 87.7-92.8), whereas sexual domain showed deterioration from 56.4 (95% CI: 52.8-59.9) to 53.7 (95% CI: 50.0-57.4). Adjusted HRQL score changes from baseline to 12-month follow-up estimated with generalized estimating equation models showed improvement on the following parameters: urinary domain after TUR with or without intravesical therapy (+3.9, 95% CI: 0.1-7.7), bowel domain among patients treated with TUR and BCG (+7.0, 95% CI: 2.4-11.5), and sexual domain among those treated with TUR and mitomycin C (+13.1, 95% CI: 5.9-20.2).For the first time, a distinctive HRQL pattern of bladder cancer treatment benefits emerges for TUR alone, and in combination with BCG or mitomycin C, which deserves further research. Treatment differences cannot be interpreted in terms of efficacy but can be useful to generate hypotheses to test in future studies.

This is the protocol for a review and there is no abstract. The objectives are as follows: Our overall aim is to provide an overview of the efficacy of interventions for obesity or overweight in adults by summarising the evidence from multiple systematic reviews.

Background Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors and has the potential to aid wound healing. Objectives To determine whether autologous PRP promotes the healing of chronic wounds. Search methods We searched the Cochrane Wounds Group Specialised Register (searched 15 August 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8); Ovid MEDLINE (1950 to August Week 1 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, August 14, 2012); Ovid EMBASE (1980 to 2012 Week 32); EBSCO CINAHL (1982 to 10 August 2012) and International Clinical Trials Registry Platform (ICTRP)(accessed 22 August 2012). No date or language restrictions were applied. Selection criteria We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. Data collection and analysis Two review authors independently assessed each study against the inclusion criteria, extracted data and assessed risk of bias for all included trials. We calculated the risk ratio (RR) or the mean difference (MD) and time to wound healing was analysed as survival data using the hazard ratio (HR). We considered heterogeneity as significant when I2 was >75%. Main results Nine eligible RCTs were included, with a total of 325 participants of whom 44% were women. The median number of participants per RCT was 26 (range 10 to 86). Four RCTs recruited people with mixed chronic wounds (there were participants with wounds caused by more than one aetiology and participants who had wounds of several aetiologies in the same trial), three RCTs recruited people with venous leg ulcers and two RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range eight to 40 weeks). One study was at low risk of bias, three studies were at high risk of bias with the remainder being at overall unclear risk of bias. The proportion of completely healed chronic wounds was reported in seven RCTs that compared PRP with standard treatment or placebo, with no statistically significant difference between the groups, in diabetic foot ulcers (RR 1.16; 95% CI 0.57 to 2.35), in venous leg ulcers (pooled RR 1.02; 95% CI 0.81 to 1.27; I2=0% ) and in mixed chronic wounds (pooled RR 1.85; 95% CI 0.76 to 4.51; I2=42%). The total area epithelialised at the end of the intervention was reported in three RCTs of mixed chronic wounds, there was no statistically significant difference between the groups (pooled MD -1.94 cm2; 95% CI -4.74 to 0.86; I2=47%). The percentage of wound area healed was reported in two RCTs of mixed chronic wounds, and results were statistically significant in favour of the PRP group (RR 51.78%; 95% CI 32.70 to 70.86; I2= 0%). Wound complications like infection or necrosis were reported by three RCTs, and there was no statistically significant difference between groups (RR 1.08; 95% CI 0.31 to 3.73). Adverse effects were reported by three studies and there was no statistically significant difference between people treated with PRP and those not given PRP (pooled RR 1.07; 95% CI 0.32 to 3.58; I2=0%). Authors' conclusions There is currently no evidence to suggest that autologous PRP is of value for treating chronic wounds. However, current evidence is based on a small number of RCTs, most of which are either at high or unclear risk of bias. Well-designed and adequately powered clinical trials are needed.

Reason for withdrawal from publication This review is out of date although it is correct as of the date of publication. The latest version is available in the ‘Other versions’ tab on The Cochrane Library, and may still be useful to readers. However, the review may be misleading as new studies could alter the original conclusions. For further information, please contact the PaPaS team at http://papas.cochrane.org/contact-us.