A sub-study of the POISE-3 randomized trial examined effects of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of acute kidney injury.

In this pre-specified sub-study of the POISE-3 trial, we examined the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of postoperative acute kidney injury (AKI). Altogether,7307 patients were included from 110 hospitals in 22 countries. Patients were 45 years and older, had or were at risk of atherosclerotic disease, took at least one antihypertensive medication, and were scheduled for noncardiac surgery. Hypotension-avoidance strategy: (i) target intraoperative mean arterial pressure (MAP) 80 mm Hg or over, (ii) on day of surgery and for two days after, hold renin-angiotensin-aldosterone system inhibitors and use other antihypertensives in stepwise fashion if systolic blood pressure (SBP) 130 mm Hg or more. Hypertension-avoidance strategy: (i) target intraoperative MAP 60 mm Hg or more, (ii) continue all antihypertensives before and after surgery. Primary outcome: postoperative AKI, an increase in serum creatinine concentration of either 26.5 µmol/L or more (0.3 mg/dL or more) within 48 hours of randomization or 50% or more within seven days of randomization. The hypotension-avoidance group (3654 patients) used fewer antihypertensive medications than the hypertension-avoidance group (3653 patients); specifically, 6% vs. 38% used an ACEI or ARB on the day of surgery, and 6% vs. 47% and 7% vs. 50% one and two days after surgery, respectively. Patients also spent about half as much intraoperative time with a MAP under 80 mm Hg (27 vs 60 minutes, respectively), but had little difference in average BP before or after surgery. There was no significant difference in AKI risk (15.1% vs. 14.4%). Results were consistent with other definitions of AKI and in patients with preexisting chronic kidney disease. Thus, a hypotension-avoidance strategy targeting a MAP greater than 80 mm Hg in the operating room and discontinued blood pressure medication during the perioperative period did not confer a lower risk of AKI compared to a hypertension avoidance strategy.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Anti-vascular endothelial growth factor for proliferative diabetic retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of the presence of new vessels in the retina and vitreous haemorrhage. Although panretinal photocoagulation (PRP) is the treatment of choice for PDR, it has secondary effects that can affect vision. 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 and summarise any relevant economic evaluations of their use. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. We did not use any date or language restrictions. We last searched the electronic databases on 1 June 2022. 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. We excluded studies that used anti-VEGFs in people undergoing vitrectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias (RoB) for all included trials. We calculated the risk ratio (RR) or the mean difference (MD), and 95% confidence intervals (CI). We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 15 new studies in this update, bringing the total to 23 RCTs with 1755 participants (2334 eyes). Forty-five per cent of participants were women and 55% were men, with a mean age of 56 years (range 48 to 77 years). The mean glycosylated haemoglobin (Hb1Ac) was 8.45% for the PRP group and 8.25% for people receiving anti-VEGFs alone or in combination. Twelve studies included people with PDR, and participants in 11 studies had high-risk PDR (HRPDR). Twelve studies were of bevacizumab, seven of ranibizumab, one of conbercept, two of pegaptanib, and one of aflibercept. The mean number of participants per RCT was 76 (ranging from 15 to 305). Most studies had an unclear or high RoB, mainly in the blinding of interventions and outcome assessors. A few studies had selective reporting and attrition bias. No study reported loss or gain of 3 or more lines of visual acuity (VA) at 12 months. Anti-VEGFs ± PRP probably increase VA compared with PRP alone (mean difference (MD) -0.08 logMAR, 95% CI -0.12 to -0.04; I2 = 28%; 10 RCTS, 1172 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may increase regression of new vessels (MD -4.14 mm2, 95% CI -6.84 to -1.43; I2 = 75%; 4 RCTS, 189 eyes; low-certainty evidence) and probably increase a complete regression of new vessels (RR 1.63, 95% CI 1.19 to 2.24; I2 = 46%; 5 RCTS, 405 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP probably reduce vitreous haemorrhage (RR 0.72, 95% CI 0.57 to 0.90; I2 = 0%; 6 RCTS, 1008 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may reduce the need for vitrectomy compared with eyes that received PRP alone (RR 0.67, 95% CI 0.49 to 0.93; I2 = 43%; 8 RCTs, 1248 eyes; low-certainty evidence). Anti-VEGFs ± PRP may result in little to no difference in the quality of life compared with PRP alone (MD 0.62, 95% CI -3.99 to 5.23; I2 = 0%; 2 RCTs, 382 participants; low-certainty evidence). We do not know if anti-VEGFs ± PRP compared with PRP alone had an impact on adverse events (very low-certainty evidence). We did not find differences in visual acuity in subgroup analyses comparing the type of anti-VEGFs, the severity of the disease (PDR versus HRPDR), time to follow-up (< 12 months versus 12 or more months), and treatment with anti-VEGFs + PRP versus anti-VEGFs alone. The main reasons for downgrading the certainty of evidence included a high RoB, imprecision, and inconsistency of effect estimates. AUTHORS' CONCLUSIONS: Anti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful. Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce the need for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence of adverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required, assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up.

Effectiveness of nonpharmacological interventions to prevent adverse events in the intensive care unit: A review of systematic reviews.

BACKGROUND: Different types of interventions have been assessed for the prevention of adverse events. However, determining which patient-safety practice is most effective can be challenging when there is no systematised evidence synthesis. An overview following the best methodological standards can provide the best reliable integrative evidence. OBJECTIVES: The objective of this study was to provide an overview of effectiveness nonpharmacological interventions aimed at preventing adverse events in the intensive care unit. METHODS: A review of systematic reviews (SRs) was conducted according to the Cochrane Handbook and PRISMA recommendations. PubMed, CINAHL, and Cochrane Library were searched for SRs published until March 2022. Two reviewers independently assessed the study's quality, using AMSTAR-2, and extracted data on intervention characteristics and effect on prevention of adverse events. RESULTS: Thirty-seven SRs were included, and 27 nonpharmacological interventions were identified to prevent 11 adverse events. Most of the reviews had critically low methodological quality. Among all the identified interventions, subglottic secretion drainage, semirecumbent position, and kinetic bed therapy were effective in preventing ventilator-associated pneumonia; the use of earplugs, early mobilisation, family participation, and music in reducing delirium; physical rehabilitation in improving muscle strength; use of respiratory support in preventing reintubation; the use of a computerised physician order entry system in reducing risk of medication errors; and the use of heated water humidifier was effective in reducing artificial airway occlusion. CONCLUSIONS: Some nonpharmacological interventions reduced adverse events in the intensive care setting. These findings should be interpreted carefully due to the low methodological quality. SRs on preventing adverse events in the intensive care unit should adhere to quality assessment tools so that best evidence can be used in decision-making.

Vaccines for the common cold.

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).

Impact of early childhood caries on oral health-related quality of life: A systematic review and meta-analysis.

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.

Interventions for treating leg ulcers in people with sickle cell disease.

BACKGROUND: The frequency of skin ulceration makes 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. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the clinical effectiveness and harms 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 January 2020), ISI Web of Knowledge (1985 to January 2020), and the Clinical Trials Search Portal of the World Health Organization (January 2020). 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: 13 January 2020; date of the last search of the Cochrane Wounds Group Trials Register: 17 February 2017. 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. We used GRADE to assess the quality of the evidence. 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® cream, arginine-glycine-aspartic acid (RGD) peptide dressing and topical antibiotics). No trials on non-pharmaceutical interventions were included in the review. All trials had an overall unclear or high risk of bias, and drug companies sponsored four of them. We were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the units of randomisation and analysis. Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, only arginine butyrate showed a reduction of ulcer size compared with a control group, mean reduction -5.10 cm² (95% CI -9.65 to -0.55), but we are uncertain whether this reduces ulcer size compared to standard care alone as the certainty of the evidence has been assessed as very low. Three trials reported on complete leg ulcer closure (isoxsuprine, arginine butyrate, RGD peptide matrix; very low quality of evidence). None reported a clinical benefit. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; incidence of amputation or harms. AUTHORS' CONCLUSIONS: Given the very low quality of the evidence identified in this updated Cochrane Review we are uncertain whether any of the assessed pharmaceutical interventions reduce ulcer size or result in leg ulcer closure in treated participants compared to controls. 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 an unclear or high risk of bias. The harm profile of the all interventions remains inconclusive.

Exercise training for adult lung transplant recipients.

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 years who 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.

CHIVA method for the treatment of chronic venous insufficiency.

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.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs 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 the second update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (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 standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.

Medication errors in prescription and administration in critically ill patients.

AIM: To determine the prevalence and magnitude of medication errors and their association with patients' sociodemographic and clinical characteristics and nurses' work conditions. DESIGN: An observational, analytical, cross-sectional and ambispective study was conducted in critically ill adult patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.

Adaptation and validation of the PEDSQL™ oral health scale for toddlers in Chilean population.

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 < 0.001); it also was lower in children with caries than in those caries-free (median 100 vs 90, p < 0.001). No statistically significant differences were found among groups according to malocclusion and traumatic dental injuries. 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.

Assessing oral health-related quality of life in children and adolescents: a systematic review and standardized comparison of available instruments.

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.

Prevention of postoperative bleeding in hip fractures treated with prosthetic replacement: efficacy and safety of fibrin sealant and tranexamic acid. A randomised controlled clinical trial (TRANEXFER study).

INTRODUCTION: We assessed the efficacy of fibrin sealant (FS) and tranexamic acid (TXA) administered topically in patients with a hip fracture treated with prosthetic replacement. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cross-cultural adaptation and psychometric evaluation of the early childhood oral health impact scale (ECOHIS) in chilean population.

BACKGROUND: The Early Childhood Oral Health Impact Scale (ECOHIS) measures the impact of dental diseases on Oral Health-Related Quality of Life both in children and their families. The aim of this study was to develop a Chilean Spanish version of the ECOHIS that is conceptually equivalent to the original and to assess its acceptability, reliability and validity in the preschool population of Chile. METHODS: The Chilean version of the ECOHIS was obtained through a process including forward and back-translation, expert panel, and cognitive debriefing interviews. To assess metric properties, a cross-sectional study was carried out in Carahue, Southern Chile (April-October 2016). Children younger than six years old without systemic diseases, disabilities or chronic medication from eleven public preschools were included. Parents were invited to complete the Chilean version of the ECOHIS, PedsQL™4.0 Generic Core and PedsQL Oral Health scales, and to answer global questions about their children's general and oral health. A subsample was administrated ECOHIS a second time 14-21 days after. A clinical examination was performed to assess dental caries, malocclusion, and traumatic dental injuries. Reliability was evaluated using measures of internal consistency (Cronbach's alpha) and reproducibility (Intraclass correlation coefficient - ICC). Construct validity was assessed by testing hypotheses based on available evidence about known groups and relationships between different instruments. RESULTS: The content comparison of the back-translation with the original ECOHIS showed that all items except one were conceptually and linguistically equivalent. The cognitive debriefing showed a suitable understanding of the Chilean version by the parents. In the total sample (n = 302), the ECOHIS total score median was 1 (IQR 6), floor effect was 41.6%, and ceiling effect 0%. Cronbach's alpha was 0.89 and the ICC was 0.84. The correlation between ECOHIS and PedsQL™4.0 Generic Core was weak (r = 0.21), while it was strong-moderate (r = 0.64) with the PedsQL Oral Health scale. In the known groups comparison, the ECOHIS total score was statistically higher in children with poor than excellent/very good oral health (median 11.6 vs 0, p < 0.01), and in the high severity than in the caries-free group (median 8 vs 0.5, p < 0.01). No differences were found according to malocclusion and traumatic dental injuries groups. CONCLUSIONS: These results supported the feasibility, reliability and validity of the Chilean version of ECOHIS questionnaire for preschool children through proxy.

Surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis.

BACKGROUND: Brain metastases occur when cancer cells spread from their original site to the brain and are a frequent cause of morbidity and death in people with cancer. They occur in 20% to 40% of people during the course of their disease. Brain metastases are also the most frequent type of brain malignancy. Single and solitary brain metastasis is infrequent and choosing the most appropriate treatment is a clinical challenge. Surgery and stereotactic radiotherapy are two options. For surgery, tumour resection is performed using microsurgical techniques, while in stereotactic radiotherapy, external ionising radiation beams are precisely focused on the brain metastasis. Stereotactic radiotherapy may be given as a single dose, also known as single dose radiosurgery, or in a number of fractions, also known as fractionated stereotactic radiotherapy. There is uncertainty regarding which treatment (surgery or stereotactic radiotherapy) is more effective for people with single or solitary brain metastasis. OBJECTIVES: To assess the effectiveness and safety of surgery versus stereotactic radiotherapy for people with single or solitary brain metastasis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2018), MEDLINE and Embase up to 25 March 2018 for relevant studies. We also searched trials databases, grey literature and handsearched relevant literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing surgery versus stereotactic radiotherapy, either a single fraction (stereotactic radiosurgery) or multiple fractions (fractionated stereotactic radiotherapy) for treatment of single or solitary brain metastasis. DATA COLLECTION AND ANALYSIS: Two review authors screened all references, evaluated the quality of the included studies using the Cochrane tool for assessing risk of bias, and performed data extraction. The primary outcomes were overall survival and adverse events. Secondary outcomes included progression-free survival and quality of life . We analysed overall survival and progression-free survival as hazard ratios (HRs) with 95% confidence intervals (CIs), and analysed adverse events as risk ratios (RRs). For quality of life we used mean difference (MD). MAIN RESULTS: Two RCTs including 85 participants met our inclusion criteria. One study included people with single untreated brain metastasis (n = 64), and the other included people with solitary brain metastasis (22 consented to randomisation and 21 were analysed). We identified a third trial reported as completed and pending results this may be included in future updates of this review. The two included studies were prematurely closed due to poor participant accrual. One study compared surgery plus whole brain radiotherapy (WBRT) versus stereotactic radiosurgery alone, and the second study compared surgery plus WBRT versus stereotactic radiosurgery plus WBRT. Meta-analysis was not possible due to clinical heterogeneity between trial interventions. The overall certainty of evidence was low or very low for all outcomes due to high risk of bias and imprecision.We found no difference in overall survival in either of the two comparisons. For the comparison of surgery plus WBRT versus stereotactic radiosurgery alone: HR 0.92, 95% CI 0.48 to 1.77; 64 participants, very low-certainty evidence. We downgraded the certainty of the evidence to very low due to risk of bias and imprecision. For the comparison of surgery plus WBRT versus stereotactic radiosurgery plus WBRT: HR 0.53, 95% CI 0.20 to 1.42; 21 participants, low-certainty evidence. We downgraded the certainty of the evidence to low due to imprecision. Adverse events were reported in both trial groups in the two studies, showing no differences for surgery plus WBRT versus stereotactic radiosurgery alone (RR 0.31, 95% CI 0.07 to 1.44; 64 participants) and for surgery plus WBRT versus stereotactic radiosurgery plus WBRT (RR 0.37, 95% CI 0.05 to 2.98; 21 participants). Most of the adverse events were related to radiation toxicities. We considered the certainty of the evidence from the two comparisons to be very low due to risk of bias and imprecision.There was no difference in progression-free survival in the study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT (HR 0.55, 95% CI 0.22 to 1.38; 21 participants, low-certainty evidence). We downgraded the evidence to low certainty due to imprecision. This outcome was not clearly reported for the other comparison. In general, there were no differences in quality of life between the two studies. The study comparing surgery plus WBRT versus stereotactic radiosurgery plus WBRT found no differences after two months using the QLQ-C30 global scale (MD -10.80, 95% CI -44.67 to 23.07; 14 participants, very low-certainty evidence). We downgraded the certainty of evidence to very low due to risk of bias and imprecision. AUTHORS' CONCLUSIONS: Currently, there is no definitive evidence regarding the effectiveness and safety of surgery versus stereotactic radiotherapy on overall survival, adverse events, progression-free survival and quality of life in people with single or solitary brain metastasis, and benefits must be decided on a case-by-case basis until well powered and designed trials are available. Given the difficulties in participant accrual, an international multicentred approach should be considered for future studies.

Vasodilators for women undergoing fertility treatment.

BACKGROUND: The rate of successful pregnancies brought to term has barely increased since the first assisted reproductive technology (ART) technique became available. Vasodilators have been proposed to increase endometrial receptivity, thicken the endometrium, and favour uterine relaxation, all of which could improve uterine receptivity and enhance the chances for successful assisted pregnancy. OBJECTIVES: To evaluate the effectiveness and safety of vasodilators in women undergoing fertility treatment. SEARCH METHODS: We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of controlled trials, the Cochrane Central Register of of Controlled Trials, via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, the Open System for Information on Grey Literature in Europe (OpenSIGLE), the Latin American and Caribbean Health Science Information Database (LILACS), clinical trial registries, and the reference lists of relevant articles. We conducted the search in October 2017 and applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing vasodilators alone or in combination with other treatments versus placebo or no treatment or versus other agents in women undergoing fertility treatment. DATA COLLECTION AND ANALYSIS: Four review authors independently selected studies, assessed risk of bias, extracted data, and calculated risk ratios (RRs). We combined study data using a fixed-effect model and assessed evidence quality using Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) methods. Our primary outcomes were live birth or ongoing pregnancy and vasodilator side effects. Secondary outcomes included clinical pregnancy, endometrial thickness, multiple pregnancy, miscarriage, and ectopic pregnancy. MAIN RESULTS: We included 15 studies with a total of 1326 women. All included studies compared a vasodilator versus placebo or no treatment. We judged most of these studies as having unclear risk of bias. Overall, the quality of evidence was low to moderate for most outcomes. The main limitations were imprecision due to low numbers of events and participants and risk of bias due to unclear methods of randomisation.Vasodilators probably make little or no difference in rates of live birth compared with placebo or no treatment (RR 1.18, 95% confidence interval (CI) 0.83 to 1.69; three RCTs; N = 350; I² = 0%; moderate-quality evidence) but probably increase overall rates of side effects including headache and tachycardia (RR 2.35, 95% CI 1.51 to 3.66; four RCTs; N = 418; I² = 0%; moderate-quality evidence). Evidence suggests that if 236 per 1000 women achieve live birth with placebo or no treatment, then between 196 and 398 per 1000 will do so with the use of vasodilators.Compared with placebo or no treatment, vasodilators may slightly improve clinical pregnancy rates (RR 1.45, 95% CI 1.19 to 1.77; 11 RCTs; N = 1054; I² = 6%; low-quality evidence). Vasodilators probably make little or no difference in rates of multiple gestation (RR 1.15, 95% CI 0.55 to 2.42; three RCTs; N = 370; I² = 0%; low-quality evidence), miscarriage (RR 0.83, 95% CI 0.37 to 1.86; three RCTs; N = 350; I² = 0%; low-quality evidence), or ectopic pregnancy (RR 1.48, 95% CI 0.25 to 8.69; two RCTs; N = 250; I² = 5%; low-quality evidence). All studies found benefit for endometrial thickening, but reported effects varied (I² = 92%) and ranged from a mean difference of 0.80 higher (95% CI 0.18 to 1.42) to 3.57 higher (95% CI 3.01 to 4.13) with very low-quality evidence, so we are uncertain how to interpret these results. AUTHORS' CONCLUSIONS: Evidence was insufficient to show whether vasodilators increase the live birth rate in women undergoing fertility treatment. However, low-quality evidence suggests that vasodilators may slightly increase clinical pregnancy rates. Moderate-quality evidence shows that vasodilators increase overall side effects in comparison with placebo or no treatment. Adequately powered studies are needed so that each treatment can be evaluated more accurately.

Dental caries prevention in children and adolescents: a systematic quality assessment of clinical practice guidelines.

OBJECTIVES: To evaluate the quality of clinical practice guidelines (CPGs) for dental caries prevention in children and adolescents MATERIALS AND METHODS: We 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). RESULTS: Twenty-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 89.6 ± 12%; Stakeholder involvement 55.0 ± 15.6%; 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.

Intensive follow-up for women with breast cancer: review of clinical, economic and patient's preference domains through evidence to decision framework.

BACKGROUND: Women treated for breast cancer are followed-up for monitoring of treatment effectiveness and for detecting recurrences at an early stage. The type of follow-up received may affect women's reassurance and impact on their quality of life. Anxiety and depression among women with breast cancer has been described, but little is known about how the intensity of the follow-up can affect women's psychological status. This study was undertaken to evaluate the effects of intensive vs. less-intensive follow-up on different health outcomes, to determine what are women's preferences and values regarding the follow-up received, and also assess the costs of these different types of follow-up. METHODS: A systematic review following standard Cochrane Collaboration methods was carried out to assess the efficacy of intensive follow-up versus non-intensive follow-up in breast cancer patients. Two additional reviews on women's preferences and economic evidence were also carried out. The search was performed up to January 2016 in: MEDLINE, EMBASE, PDQ, McMaster Health Systems Evidence, CENTRAL, and NHS EED (through The Cochrane Library). The quality of evidence was assessed by GRADE (for quantitative studies) and CerQUAL (for qualitative studies). Several outcomes including mortality, breast cancer recurrences, quality of life, and patient satisfaction were evaluated. RESULTS: Six randomised trials (corresponding to 3534 women) were included for the evaluation of health outcomes; three studies were included for women's values and preferences and four for an economic assessment. There is moderate certainty of evidence showing that intensive follow-up, including more frequent diagnostic tests or visits, does not have effects on 5- or 10-year overall mortality and recurrences in women with breast cancer, compared with less intensive follow-up. Regarding women's preferences and values, there was important variability among studies and within studies (low confidence due to risk of bias and inconsistency). Furthermore, intensive follow-up, as opposed to less intensive follow-up, is not likely to be cost-effective. CONCLUSIONS: Less intensive follow-up appears to be justified and can be recommended over intensive follow-up. Resources could thus be mobilised to other aspects of breast cancer care, or other areas of healthcare.

WITHDRAWN: Radioisotopes for metastatic bone pain.

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 (89Sr) with Samarium-153 (153Sm), Rhenium-186 (186Re) and Phosphorus-32 (32P). We observed no significant differences between treatments. Similarly, we observed no differences when we compared different doses of 153Sm (0.5 versus 1.0 mCi). AUTHORS' CONCLUSIONS: This update adds new evidence on efficacy of radioisotopes versus placebo, 89Sr compared with other radioisotopes, and dose-comparisons of 153Sm and 188Re. 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.