Diagnostic accuracy of ultrasound screening for fetal structural abnormalities during the first and second trimester of pregnancy in low-risk and unselected populations.

BACKGROUND: Prenatal ultrasound is widely used to screen for structural anomalies before birth. While this is traditionally done in the second trimester, there is an increasing use of first-trimester ultrasound for early detection of lethal and certain severe structural anomalies. OBJECTIVES: To evaluate the diagnostic accuracy of ultrasound in detecting fetal structural anomalies before 14 and 24 weeks' gestation in low-risk and unselected pregnant women and to compare the current two main prenatal screening approaches: a single second-trimester scan (single-stage screening) and a first- and second-trimester scan combined (two-stage screening) in terms of anomaly detection before 24 weeks' gestation. SEARCH METHODS: We searched MEDLINE, EMBASE, Science Citation Index Expanded (Web of Science), Social Sciences Citation Index (Web of Science), Arts & Humanities Citation Index and Emerging Sources Citation Index (Web of Science) from 1 January 1997 to 22 July 2022. We limited our search to studies published after 1997 and excluded animal studies, reviews and case reports. No further restrictions were applied. We also screened reference lists and citing articles of each of the included studies. SELECTION CRITERIA: Studies were eligible if they included low-risk or unselected pregnant women undergoing a first- and/or second-trimester fetal anomaly scan, conducted at 11 to 14 or 18 to 24 weeks' gestation, respectively. The reference standard was detection of anomalies at birth or postmortem. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook study selection, quality assessment (QUADAS-2), data extraction and evaluation of the certainty of evidence (GRADE approach). We used univariate random-effects logistic regression models for the meta-analysis of sensitivity and specificity. MAIN RESULTS: Eighty-seven studies covering 7,057,859 fetuses (including 25,202 with structural anomalies) were included. No study was deemed low risk across all QUADAS-2 domains. Main methodological concerns included risk of bias in the reference standard domain and risk of partial verification. Applicability concerns were common in studies evaluating first-trimester scans and two-stage screening in terms of patient selection due to frequent recruitment from single tertiary centres without exclusion of referrals. We reported ultrasound accuracy for fetal structural anomalies overall, by severity, affected organ system and for 46 specific anomalies. Detection rates varied widely across categories, with the highest estimates of sensitivity for thoracic and abdominal wall anomalies and the lowest for gastrointestinal anomalies across all tests. The summary sensitivity of a first-trimester scan was 37.5% for detection of structural anomalies overall (95% confidence interval (CI) 31.1 to 44.3; low-certainty evidence) and 91.3% for lethal anomalies (95% CI 83.9 to 95.5; moderate-certainty evidence), with an overall specificity of 99.9% (95% CI 99.9 to 100; low-certainty evidence). Two-stage screening had a combined sensitivity of 83.8% (95% CI 74.7 to 90.1; low-certainty evidence), while single-stage screening had a sensitivity of 50.5% (95% CI 38.5 to 62.4; very low-certainty evidence). The specificity of two-stage screening was 99.9% (95% CI 99.7 to 100; low-certainty evidence) and for single-stage screening, it was 99.8% (95% CI 99.2 to 100; moderate-certainty evidence). Indirect comparisons suggested superiority of two-stage screening across all analyses regarding sensitivity, with no significant difference in specificity. However, the certainty of the evidence is very low due to the absence of direct comparisons. AUTHORS' CONCLUSIONS: A first-trimester scan has the potential to detect lethal and certain severe anomalies with high accuracy before 14 weeks' gestation, despite its limited overall sensitivity. Conversely, two-stage screening shows high accuracy in detecting most fetal structural anomalies before 24 weeks' gestation with high sensitivity and specificity. In a hypothetical cohort of 100,000 fetuses, the first-trimester scan is expected to correctly identify 113 out of 124 fetuses with lethal anomalies (91.3%) and 665 out of 1776 fetuses with any anomaly (37.5%). However, 79 false-positive diagnoses are anticipated among 98,224 fetuses (0.08%). Two-stage screening is expected to correctly identify 1448 out of 1776 cases of structural anomalies overall (83.8%), with 118 false positives (0.1%). In contrast, single-stage screening is expected to correctly identify 896 out of 1776 cases before 24 weeks' gestation (50.5%), with 205 false-positive diagnoses (0.2%). This represents a difference of 592 fewer correct identifications and 88 more false positives compared to two-stage screening. However, it is crucial to acknowledge the uncertainty surrounding the additional benefits of two-stage versus single-stage screening, as there are no studies directly comparing them. Moreover, the evidence supporting the accuracy of first-trimester ultrasound and two-stage screening approaches primarily originates from studies conducted in single tertiary care facilities, which restricts the generalisability of the results of this meta-analysis to the broader population.

Calcium supplementation for people with overweight or obesity.

BACKGROUND: Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends. OBJECTIVES: To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months. We included the following comparisons: calcium supplementation versus placebo, calcium-fortified food or beverage versus placebo, or calcium-fortified food or beverage versus non-calcium-fortified food or beverage. We excluded studies that evaluated the effect of calcium and vitamin D or mixed minerals compared to placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were body weight, health-related quality of life, and adverse events. Our secondary outcomes were anthropometric measures other than body weight, all-cause mortality, and morbidity. MAIN RESULTS: We found 18 studies that evaluated the effect of calcium compared to placebo or control, with a total of 1873 randomised participants (950 participants in the calcium supplementation groups and 923 in the control groups). All included studies gave oral calcium supplementation as the intervention. We did not find any studies evaluating calcium-fortified foods. We excluded 38 studies, identified four ongoing studies, and listed one study as 'awaiting classification'. Sixteen studies compared calcium supplementation to placebo; two studies compared different doses of calcium supplementation. Doses ranged from very low (0.162 g of calcium/day) to high (1.5 g of calcium/day). Most studies were performed in the USA and Iran, lasted less than six months, and included only women. Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in little to no difference in body weight (mean difference (MD) -0.15 kg, 95% confidence interval (CI) -0.55 to 0.24; P = 0.45, I2 = 46%; 17 studies, 1317 participants; low-certainty evidence). We downgraded the certainty of the evidence by two levels for risk of bias and heterogeneity. None of the included studies reported health-related quality of life, all-cause mortality, or morbidity/complications as outcomes. Only five studies assessed or reported adverse events. Low-certainty evidence suggests a low frequency of adverse events, with no clear difference between intervention and control groups. Moderate-certainty evidence shows that calcium supplementation compared to placebo or control probably results in a small reduction in body mass index (BMI) (MD -0.18 kg/m2,95% CI -0.22 to -0.13; P < 0.001, I2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I2 = 0%; 6 studies, 273 participants). Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in a small reduction in body fat mass (MD -0.34 kg, 95% CI -0.73 to 0.05; P < 0.001, I2 = 97%; 12 studies, 812 participants). AUTHORS' CONCLUSIONS: Calcium supplementation for eight weeks to 24 months may result in little to no difference in body weight in people with overweight or obesity. The current evidence is of low certainty, due to concerns regarding risk of bias and statistical heterogeneity. We found that the degree of heterogeneity might be partly explained by calcium dosage, the presence or absence of a co-intervention, and whether an intention-to-treat analysis was pursued. While our analyses suggest that calcium supplementation may result in a small reduction in BMI, waist circumference, and fat mass, this evidence is of low to moderate certainty. Future studies could investigate the effect of calcium supplementation on lean body mass to explore if there is a change in body composition.

Evaluating bias and noise induced by the U.S. Census Bureau's privacy protection methods.

The U.S. Census Bureau faces a difficult trade-off between the accuracy of Census statistics and the protection of individual information. We conduct an independent evaluation of bias and noise induced by the Bureau's two main disclosure avoidance systems: the TopDown algorithm used for the 2020 Census and the swapping algorithm implemented for the three previous Censuses. Our evaluation leverages the Noisy Measurement File (NMF) as well as two independent runs of the TopDown algorithm applied to the 2010 decennial Census. We find that the NMF contains too much noise to be directly useful without measurement error modeling, especially for Hispanic and multiracial populations. TopDown's postprocessing reduces the NMF noise and produces data whose accuracy is similar to that of swapping. While the estimated errors for both TopDown and swapping algorithms are generally no greater than other sources of Census error, they can be relatively substantial for geographies with small total populations.

Daratumumab and antineoplastic therapy versus antineoplastic therapy only for adults with newly diagnosed multiple myeloma ineligible for transplant.

BACKGROUND: Multiple myeloma (MM) is a haematological malignancy that is characterised by proliferation of malignant plasma cells in the bone marrow. For adults ineligible to receive high-dose chemotherapy and autologous stem cell transplant, the recommended treatment combinations in first-line therapy generally consist of combinations of alkylating agents, immunomodulatory drugs, and proteasome inhibitors. Daratumumab is a CD38-targeting, human IgG1k monoclonal antibody recently developed and approved for the treatment of people diagnosed with MM. Multiple myeloma cells uniformly over-express CD-38, a 46-kDa type II transmembrane glycoprotein, making myeloma cells a specific target for daratumumab. OBJECTIVES: To determine the benefits and harms of daratumumab in addition to antineoplastic therapy compared to antineoplastic therapy only for adults with newly diagnosed MM who are ineligible for transplant. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, EU Clinical Trials Register, ClinicalTrials.gov, WHO ICTRP, and conference proceedings from 2010 to September 2023. SELECTION CRITERIA: We included randomised controlled trials that compared treatment with daratumumab added to antineoplastic therapy versus the same antineoplastic therapy alone in adult participants with a confirmed diagnosis of MM. We excluded quasi-randomised trials and trials with less than 80% adult participants, unless there were subgroup analyses of adults with MM. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the search strategies for eligibility. We documented the process of study selection in a flowchart as recommended by the PRISMA statement. We evaluated the risk of bias in included studies with RoB 1 and assessed the certainty of the evidence using GRADE. We followed standard Cochrane methodological procedures. MAIN RESULTS: We included four open-label, two-armed randomised controlled trials (34 publications) involving a total of 1783 participants. The ALCYONE, MAIA, and OCTANS trials were multicentre trials conducted worldwide in middle- and high-income countries. The AMaRC 03-16 trial was conducted in one high-income country, Australia. The mean age of participants was 69 to 74 years, and the proportion of female participants was between 40% and 54%. All trials evaluated antineoplastic therapies with or without daratumumab. In the ALCYONE and OCTANS trials, daratumumab was combined with bortezomib and melphalan-prednisone. In the AMaRC 03-16 study, it was combined with bortezomib, cyclophosphamide, and dexamethasone, and in the MAIA study, it was combined with lenalidomide and dexamethasone. None of the included studies was blinded (high risk of performance and detection bias). One study was published as abstract only, therefore the risk of bias for most criteria was unclear. The other three studies were published as full texts. Apart from blinding, the risk of bias was low for these studies. Overall survival Treatment with daratumumab probably increases overall survival when compared to the same treatment without daratumumab (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.53 to 0.76, 2 studies, 1443 participants, moderate-certainty evidence). After a follow-up period of 36 months, 695 per 1000 participants survived in the control group, whereas 792 per 1000 participants survived in the daratumumab group (95% CI 758 to 825). Progression-free survival Treatment with daratumumab probably increases progression-free survival when compared to treatment without daratumumab (HR 0.48, 95% CI 0.39 to 0.58, 3 studies, 1663 participants, moderate-certainty evidence). After a follow-up period of 24 months, progression-free survival was reached in 494 per 1000 participants in the control group versus 713 per 1000 participants in the daratumumab group (95% CI 664 to 760). Quality of life Treatment with daratumumab may result in a very small increase in quality of life after 12 months, evaluated on the EORTC QLQ-C30 global health status scale (GHS), when compared to treatment without daratumumab (mean difference 2.19, 95% CI -0.13 to 4.51, 3 studies, 1096 participants, low-certainty evidence). The scale is from 0 to 100, with a higher value indicating a better quality of life. On-study mortality Treatment with daratumumab probably decreases on-study mortality when compared to treatment without daratumumab (risk ratio (RR) 0.72, 95% CI 0.62 to 0.83, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 366 per 1000 participants in the control group and 264 per 1000 participants in the daratumumab group died (95% CI 227 to 304). Serious adverse events Treatment with daratumumab probably increases serious adverse events when compared to treatment without daratumumab (RR 1.18, 95% CI 1.02 to 1.37, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 505 per 1000 participants in the control group versus 596 per 1000 participants in the daratumumab group experienced serious adverse events (95% CI 515 to 692). Adverse events (Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3) Treatment with daratumumab probably results in little to no difference in adverse events (CTCAE grade ≥ 3) when compared to treatment without daratumumab (RR 1.01, 95% CI 0.99 to 1.02, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 953 per 1000 participants in the control group versus 963 per 1000 participants in the daratumumab group experienced adverse events (CTCAE grade ≥ 3) (95% CI 943 to 972). Treatment with daratumumab probably increases the risk of infections (CTCAE grade ≥ 3) when compared to treatment without daratumumab (RR 1.52, 95% CI 1.30 to 1.78, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 224 per 1000 participants in the control group versus 340 per 1000 participants in the daratumumab group experienced infections (CTCAE grade ≥ 3) (95% CI 291 to 399). AUTHORS' CONCLUSIONS: Overall analysis of four studies showed a potential benefit for daratumumab in terms of overall survival and progression-free survival and a slight potential benefit in quality of life. Participants treated with daratumumab probably experience increased serious adverse events. There were likely no differences between groups in adverse events (CTCAE grade ≥ 3); however, there are probably more infections (CTCAE grade ≥ 3) in participants treated with daratumumab. We identified six ongoing studies which might strengthen the certainty of evidence in a future update of this review.

Personal protective equipment for preventing asbestos exposure in workers.

BACKGROUND: Asbestos exposure can lead to asbestos-related diseases. The European Union (EU) has adopted regulations for workplaces where asbestos is present. The EU occupational exposure limit (OEL) for asbestos is 0.1 fibres per cubic centimetre of air (f/cm3) as an eight-hour average. Different types of personal protective equipment (PPE) are available to provide protection and minimise exposure; however, their effectiveness is unclear. OBJECTIVES: To assess the effects of personal protective equipment (PPE), including donning and doffing procedures and individual hygienic behaviour, compared to no availability and use of such equipment or alternative equipment, on asbestos exposure in workers in asbestos demolition and repair work. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, and Scopus (September 2022), and we checked the reference lists of included studies. SELECTION CRITERIA: We included studies that measured asbestos concentration outside and inside PPE (considering outside concentration a surrogate for no PPE), exposure to asbestos after doffing PPE, donning and doffing errors, nonadherence to regulations, and adverse effects of PPE. DATA COLLECTION AND ANALYSIS: Two review authors selected studies, extracted data, and assessed risk of bias using ROBINS-I. We categorised PPE as full-face filtering masks, supplied air respirators (SARs), and powered air-purifying respirators (PAPRs). Values for asbestos outside and inside PPE were transformed to logarithmic values for random-effects meta-analysis. Pooled logarithmic mean differences (MDs) were exponentiated to obtain the ratio of means (RoM) and 95% confidence interval (95% CI). The RoM shows the degree of protection provided by the respirators (workplace protection factor). Since the RoM is likely to be much higher at higher outside concentrations, we presented separate results according to the outside asbestos concentration, as follows. • Below 0.01 f/cm3 (band 1) • 0.01 f/cm3 to below 0.1 f/cm3 (band 2) • 0.1 f/cm3 to below 1 f/cm3 (band 3) • 1 f/cm3 to below 10 f/cm3 (band 4) • 10 f/cm3 to below 100 f/cm3 (band 5) • 100 f/cm3 to below 1000 f/cm3 (band 6) Additionally, we determined whether the inside concentrations per respirator and concentration band complied with the current EU OEL (0.1 f/cm3) and proposed EU OEL (0.01 f/cm3). MAIN RESULTS: We identified six studies that measured asbestos concentrations outside and inside respiratory protective equipment (RPE) and one cross-over study that compared the effect of two different coveralls on body temperature. No studies evaluated the remaining predefined outcomes. Most studies were at overall moderate risk of bias due to insufficient reporting. The cross-over study was at high risk of bias. Full-face filtering masks Two studies evaluated full-face filtering masks. They provided insufficient data for band 1 and band 6. The results for the remaining bands were as follows. • Band 2: RoM 19 (95% CI 17.6 to 20.1; 1 study, 3 measurements; moderate certainty) • Band 3: RoM 69 (95% CI 26.6 to 175.9; 2 studies, 17 measurements; very low certainty) • Band 4: RoM 455 (95% CI 270.4 to 765.1; 1 study, 16 measurements; low certainty) • Band 5: RoM 2752 (95% CI 1236.5 to 6063.2;1 study, 3 measurements; low certainty) The inside measurements in band 5 did not comply with the EU OEL of 0.1 f/cm3, and no inside measurements complied with the proposed EU OEL of 0.01 f/cm3. Supplied air respirators Two studies evaluated supplied air respirators. They provided no data for band 6. The results for the remaining bands were as follows. • Band 1: RoM 11 (95% CI 7.6 to 14.9; 1 study, 134 measurements; moderate certainty) • Band 2: RoM 63 (95% CI 43.8 to 90.9; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 528 (95% CI 368.7 to 757.5; 1 study, 38 measurements; moderate certainty) • Band 4: RoM 4638 (95% CI 3071.7 to 7044.5; 1 study, 49 measurements; moderate certainty) • Band 5: RoM 26,134 (16,647.2 to 41,357.1; 1 study, 22 measurements; moderate certainty) All inside measurements complied with the current OEL of 0.1 f/cm3 and the proposed OEL of 0.01 f/cm3. Powered air-purifying respirators Three studies evaluated PAPRs. The results per band were as follows. • Band 1: RoM 8 (95% CI 3.7 to 19.1; 1 study, 23 measurements; moderate certainty) • Band 2: RoM 90 (95% CI 64.7 to 126.5; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 104 (95% CI 23.1 to 464.1; 3 studies, 14 measurements; very low certainty) • Band 4: RoM 706 (95% CI 219.2 to 2253.0; 2 studies, 43 measurements; very low certainty) • Band 5: RoM 1366 (544.6 to 3428.9; 2 studies, 8 measurements; low certainty) • Band 6: RoM 18,958 (95% CI 4023.9 to 90,219.4; 2 studies, 13 measurements; very low certainty) All inside measurements complied with the 0.1 f/cm3 OEL when the outside concentration was below 10 f/cm3 (band 1 to band 4). From band 3, no measurements complied with the proposed OEL of 0.01 f/cm3. Different types of coveralls One study reported the adverse effects of coveralls. A polyethylene suit may increase the body temperature more than a ventilated impermeable polyvinyl (PVC) coverall, but the evidence is very uncertain (MD 0.17 °C, 95% CI -0.08 to 0.42; 1 study, 11 participants; very low certainty). AUTHORS' CONCLUSIONS: Where the outside asbestos concentration is below 0.1 f/cm3, SARS and PAPRs likely reduce exposure to below the proposed OEL of 0.01 f/cm3. For outside concentrations up to 10 f/cm3, all respirators may reduce exposure below the current OEL, but only SAR also below the proposed OEL. In band 5 (10 to < 100 f/cm3), full-face filtering masks may not reduce asbestos exposure below either OEL, SARs likely reduce exposure below both OELs, and there were no data for PAPRs. In band 6 (100 f/cm3 to < 1000 f/cm3), PAPRs may not reduce exposure below either OEL, and there were no data for full-face filtering masks or SARs. Some coveralls may increase body temperature more than others. Randomised studies are needed to directly compare PAPRs and SARs at higher asbestos concentrations and to assess adverse effects. Future studies should assess the effects of doffing procedures.

Non-invasive high-frequency ventilation in newborn infants with respiratory distress.

BACKGROUND: Respiratory distress occurs in up to 7% of newborns, with respiratory support (RS) provided invasively via an endotracheal (ET) tube or non-invasively via a nasal interface. Invasive ventilation increases the risk of lung injury and chronic lung disease (CLD). Using non-invasive strategies, with or without minimally invasive surfactant, may reduce the need for mechanical ventilation and the risk of lung damage in newborn infants with respiratory distress. OBJECTIVES: To evaluate the benefits and harms of nasal high-frequency ventilation (nHFV) compared to invasive ventilation via an ET tube or other non-invasive ventilation methods on morbidity and mortality in preterm and term infants with or at risk of respiratory distress. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and three trial registries in April 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster- or quasi-RCTs of nHFV in newborn infants with respiratory distress compared to invasive or non-invasive ventilation. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials for inclusion, extracted data, assessed the risk of bias, and undertook GRADE assessment. MAIN RESULTS: We identified 33 studies, mostly in low- to middle-income settings, that investigated this therapy in 5068 preterm and 46 term infants. nHFV compared to invasive respiratory therapy for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 0.67, 95% CI 0.20 to 2.18; 1 study, 80 infants) or the incidence of CLD (RR 0.38, 95% CI 0.09 to 1.59; 2 studies, 180 infants), both very low-certainty. ET intubation, death or CLD, severe intraventricular haemorrhage (IVH) and neurodevelopmental disability (ND) were not reported. nHFV vs nasal continuous positive airway pressure (nCPAP) used for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 1.00, 95% CI 0.41 to 2.41; 4 studies, 531 infants; very low-certainty). nHFV may reduce ET intubation (RR 0.52, 95% CI 0.33 to 0.82; 5 studies, 571 infants), but there may be little or no difference in CLD (RR 1.35, 95% CI 0.80 to 2.27; 4 studies, 481 infants); death or CLD (RR 2.50, 95% CI 0.52 to 12.01; 1 study, 68 participants); or severe IVH (RR 1.17, 95% CI 0.36 to 3.78; 4 studies, 531 infants), all low-certainty evidence. ND was not reported. nHFV vs nasal intermittent positive-pressure ventilation (nIPPV) used for initial RS nHFV may result in little to no difference in mortality before hospital discharge (RR 1.86, 95% CI 0.90 to 3.83; 2 studies, 84 infants; low-certainty). nHFV may have little or no effect in reducing ET intubation (RR 1.33, 95% CI 0.76 to 2.34; 5 studies, 228 infants; low-certainty). There may be a reduction in CLD (RR 0.63, 95% CI 0.42 to 0.95; 5 studies, 307 infants; low-certainty). A single study (36 infants) reported no events for severe IVH. Death or CLD and ND were not reported. nHFV vs high-flow nasal cannula (HFNC) used for initial RS We are very uncertain whether nHFV reduces ET intubation (RR 2.94, 95% CI 0.65 to 13.27; 1 study, 37 infants) or reduces CLD (RR 1.18, 95% CI 0.46 to 2.98; 1 study, 37 participants), both very low-certainty. There were no mortality events before hospital discharge or severe IVH. Other deaths, CLD and ND, were not reported. nHFV vs nCPAP used for RS following planned extubation nHFV probably results in little or no difference in mortality before hospital discharge (RR 0.92, 95% CI 0.52 to 1.64; 6 studies, 1472 infants; moderate-certainty). nHFV may result in a reduction in ET reintubation (RR 0.42, 95% CI 0.35 to 0.51; 11 studies, 1897 infants) and CLD (RR 0.78, 95% CI 0.67 to 0.91; 10 studies, 1829 infants), both low-certainty. nHFV probably has little or no effect on death or CLD (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 966 infants) and severe IVH (RR 0.80, 95% CI 0.57 to 1.13; 3 studies, 1117 infants), both moderate-certainty. We are very uncertain whether nHFV reduces ND (RR 0.92, 95% CI 0.37 to 2.29; 1 study, 74 infants; very low-certainty). nHFV versus nIPPV used for RS following planned extubation nHFV may have little or no effect on mortality before hospital discharge (RR 1.83, 95% CI 0.70 to 4.79; 2 studies, 984 infants; low-certainty). There is probably a reduction in ET reintubation (RR 0.69, 95% CI 0.54 to 0.89; 6 studies, 1364 infants), but little or no effect on CLD (RR 0.88, 95% CI 0.75 to 1.04; 4 studies, 1236 infants); death or CLD (RR 0.92, 95% CI 0.79 to 1.08; 3 studies, 1070 infants); or severe IVH (RR 0.78, 95% CI 0.55 to 1.10; 4 studies, 1162 infants), all moderate-certainty. One study reported there might be no difference in ND (RR 0.88, 95% CI 0.35 to 2.16; 1 study, 72 infants; low-certainty). nHFV versus nIPPV following initial non-invasive RS failure nHFV may have little or no effect on mortality before hospital discharge (RR 1.44, 95% CI 0.10 to 21.33); or ET intubation (RR 1.23, 95% CI 0.51 to 2.98); or CLD (RR 1.01, 95% CI 0.70 to 1.47); or severe IVH (RR 0.47, 95% CI 0.02 to 10.87); 1 study, 39 participants, all low- or very low-certainty. Other deaths or CLD and ND were not reported. AUTHORS' CONCLUSIONS: For initial RS, we are very uncertain if using nHFV compared to invasive respiratory therapy affects clinical outcomes. However, nHFV may reduce intubation when compared to nCPAP. For planned extubation, nHFV may reduce the risk of reintubation compared to nCPAP and nIPPV. nHFV may reduce the risk of CLD when compared to nCPAP. Following initial non-invasive respiratory support failure, nHFV when compared to nIPPV may result in little to no difference in intubation. Large trials, particularly in high-income settings, are needed to determine the role of nHFV in initial RS and following the failure of other non-invasive respiratory support. Also, the optimal settings of nHVF require further investigation.

Risk assessment for aggressive behaviour in schizophrenia.

BACKGROUND: Aggressive or violent behaviour is often associated with people with schizophrenia in common perceptions of the disease. Risk assessment methods have been used to identify and evaluate the behaviour of those individuals who are at the greatest risk of perpetrating aggression or violence or characterise the likelihood to commit acts. Although many different interventions have been developed to decrease aggressive or violent incidences in inpatient care, staff working in inpatient settings seek easy-to-use methods to decrease patient aggressive events. However, many of these are time-consuming, and they require intensive training for staff and patient monitoring. It has also been recognised in clinical practice that if staff monitor patients' behaviour in a structured manner, the monitoring itself may result in a reduction of aggressive/violent behaviour and incidents in psychiatric settings. OBJECTIVES: To assess the effects of structured aggression or violence risk assessment methods for people with schizophrenia or schizophrenia-like illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ISRCTN registry, ClinicalTrials.gov, and WHO ICTRP, on 10 February 2021. We also inspected references of all identified studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing structured risk assessment methods added to standard professional care with standard professional care for the evaluation of aggressive or violent behaviour among people with schizophrenia. DATA COLLECTION AND ANALYSIS: At least two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and its 95% CI. We assessed risk of bias in the included studies and created a summary of findings table using the GRADE approach. MAIN RESULTS: We included four studies in the review. The total number of participants was not identifiable, as some studies provided number of participants included, and some only patient days. The studies compared a package of structured assessment methods with a control group that included routine nursing care and drug therapy or unstructured psychiatric observations/treatment based on clinical judgement. In two studies, information about treatment in control care was not available. One study reported results for our primary outcome, clinically important change in aggressive/violent behaviour, measured by the rate of severe aggression events. There was likely a positive effect favouring structured risk assessment over standard professional care (RR 0.59, 95% CI 0.41 to 0.85; 1 RCT; 1852 participants; corrected for cluster design: RR 0.59, 95% CI 0.37 to 0.93; moderate-certainty evidence). One trial reported data for the use of coercive measures (seclusion room). Compared to standard professional care, structured risk assessment may have little or no effect on use of seclusion room as days (corrected for cluster design: RR 0.92, 95% CI 0.27 to 3.07; N = 20; low-certainty evidence) or use of seclusion room as secluded participants (RR 1.83, 95% CI 0.39 to 8.7; 1 RCT; N = 20; low-certainty evidence). However, seclusion room may be used less frequently in the standard professional care group compared to the structured risk assessment group (incidence) (corrected for cluster design: RR 1.63, 95% CI 0.49 to 5.47; 1 RCT; N = 20; substantial heterogeneity, Chi2 = 0.0; df = 0.0; P = 0.0; I2 = 100%; low-certainty evidence). There was no evidence of a clear effect on adverse events of escape (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence); fall down (RR 0.33, 95% CI 0.04 to 3.15; 1 RCT; n = 200; very low-certainty evidence); or choking (RR 0.2, 95% CI 0.01 to 4.11; 1 RCT; n = 200; very low-certainty evidence) when comparing structured risk assessment to standard professional care. There were no useable data for patient-related outcomes such as global state, acceptance of treatment, satisfaction with treatment, quality of life, service use, or costs. AUTHORS' CONCLUSIONS: Based on the available evidence, it is not possible to conclude that structured aggression or violence risk assessment methods are effective for people with schizophrenia or schizophrenia-like illnesses. Future work should combine the use of interventions and structured risk assessment methods to prevent aggressive incidents in psychiatric inpatient settings.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in infants. Maternal RSV vaccination is a preventive strategy of great interest, as it could have a substantial impact on infant RSV disease burden. In recent years, the clinical development of maternal RSV vaccines has advanced rapidly. OBJECTIVES: To assess the efficacy and safety of maternal respiratory syncytial virus (RSV) vaccination for preventing RSV disease in infants. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register and two other trials registries on 21 October 2022. We updated the search on 27 July 2023, when we searched MEDLINE, Embase, CENTRAL, CINAHL, and two trials registries. Additionally, we searched the reference lists of retrieved studies and conference proceedings. There were no language restrictions on our searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing maternal RSV vaccination with placebo or no intervention in pregnant women of any age. The primary outcomes were hospitalisation with clinically confirmed or laboratory-confirmed RSV disease in infants. The secondary outcomes covered adverse pregnancy outcomes (intrauterine growth restriction, stillbirth, and maternal death) and adverse infant outcomes (preterm birth, congenital abnormalities, and infant death). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (25 study reports) involving 17,991 pregnant women. The intervention was an RSV pre-F protein vaccine in four studies, and an RSV F protein nanoparticle vaccine in two studies. In all studies, the comparator was a placebo (saline, formulation buffer, or sterile water). We judged four studies at overall low risk of bias and two studies at overall high risk (mainly due to selection bias). All studies were funded by pharmaceutical companies. Maternal RSV vaccination compared with placebo reduces infant hospitalisation with laboratory-confirmed RSV disease (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.31 to 0.82; 4 RCTs, 12,216 infants; high-certainty evidence). Based on an absolute risk with placebo of 22 hospitalisations per 1000 infants, our results represent 11 fewer hospitalisations per 1000 infants from vaccinated pregnant women (15 fewer to 4 fewer). No studies reported infant hospitalisation with clinically confirmed RSV disease. Maternal RSV vaccination compared with placebo has little or no effect on the risk of congenital abnormalities (RR 0.96, 95% CI 0.88 to 1.04; 140 per 1000 with placebo, 5 fewer per 1000 with RSV vaccination (17 fewer to 6 more); 4 RCTs, 12,304 infants; high-certainty evidence). Maternal RSV vaccination likely has little or no effect on the risk of intrauterine growth restriction (RR 1.32, 95% CI 0.75 to 2.33; 3 per 1000 with placebo, 1 more per 1000 with RSV vaccination (1 fewer to 4 more); 4 RCTs, 12,545 pregnant women; moderate-certainty evidence). Maternal RSV vaccination may have little or no effect on the risk of stillbirth (RR 0.81, 95% CI 0.38 to 1.72; 3 per 1000 with placebo, no difference with RSV vaccination (2 fewer to 3 more); 5 RCTs, 12,652 pregnant women). There may be a safety signal warranting further investigation related to preterm birth. This outcome may be more likely with maternal RSV vaccination, although the 95% CI includes no effect, and the evidence is very uncertain (RR 1.16, 95% CI 0.99 to 1.36; 6 RCTs, 17,560 infants; very low-certainty evidence). Based on an absolute risk of 51 preterm births per 1000 infants from pregnant women who received placebo, there may be 8 more per 1000 infants from pregnant women with RSV vaccination (1 fewer to 18 more). There was one maternal death in the RSV vaccination group and none in the placebo group. Our meta-analysis suggests that RSV vaccination compared with placebo may have little or no effect on the risk of maternal death (RR 3.00, 95% CI 0.12 to 73.50; 3 RCTs, 7977 pregnant women; low-certainty evidence). The effect of maternal RSV vaccination on the risk of infant death is very uncertain (RR 0.81, 95% CI 0.36 to 1.81; 6 RCTs, 17,589 infants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The findings of this review suggest that maternal RSV vaccination reduces laboratory-confirmed RSV hospitalisations in infants. There are no safety concerns about intrauterine growth restriction and congenital abnormalities. We must be careful in drawing conclusions about other safety outcomes owing to the low and very low certainty of the evidence. The evidence available to date suggests RSV vaccination may have little or no effect on stillbirth, maternal death, and infant death (although the evidence for infant death is very uncertain). However, there may be a safety signal warranting further investigation related to preterm birth. This is driven by data from one trial, which is not fully published yet. The evidence base would be much improved by more RCTs with substantial sample sizes and well-designed observational studies with long-term follow-up for assessment of safety outcomes. Future studies should aim to use standard outcome measures, collect data on concomitant vaccines, and stratify data by timing of vaccination, gestational age at birth, race, and geographical setting.

Effects of additional exercise therapy after a successful vascular intervention for people with symptomatic peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is characterised by obstruction or narrowing of the large arteries of the lower limbs, usually caused by atheromatous plaques. Most people with PAD who experience intermittent leg pain (intermittent claudication) are typically treated with secondary prevention strategies, including medical management and exercise therapy. Lower limb revascularisation may be suitable for people with significant disability and those who do not show satisfactory improvement after conservative treatment. Some studies have suggested that lower limb revascularisation for PAD may not confer significantly more benefits than supervised exercise alone for improved physical function and quality of life. It is proposed that supervised exercise therapy as adjunctive treatment after successful lower limb revascularisation may confer additional benefits, surpassing the effects conferred by either treatment alone. OBJECTIVES: To assess the effects of a supervised exercise programme versus standard care following successful lower limb revascularisation in people with PAD. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, two other databases, and two trial registers, most recently on 14 March 2023. SELECTION CRITERIA: We included randomised controlled trials which compared supervised exercise training following lower limb revascularisation with standard care following lower limb revascularisation in adults (18 years and older) with PAD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were maximum walking distance or time (MWD/T) on the treadmill, six-minute walk test (6MWT) total distance, and pain-free walking distance or time (PFWD/T) on the treadmill. Our secondary outcomes were changes in the ankle-branchial index, all-cause mortality, changes in health-related quality-of-life scores, reintervention rates, and changes in subjective measures of physical function. We analysed continuous data by determining the mean difference (MD) and 95% confidence interval (CI), and dichotomous data by determining the odds ratio (OR) with corresponding 95% CI. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified seven studies involving 376 participants. All studies involved participants who received either additional supervised exercise or standard care after lower limb revascularisation. The studies' exercise programmes varied, and included supervised treadmill walking, combined exercise, and circuit training. The duration of exercise therapy ranged from six weeks to six months; follow-up time ranged from six weeks to five years. Standard care also varied between studies, including no treatment or advice to stop smoking, lifestyle modifications, or best medical treatment. We classified all studies as having some risk of bias concerns. The certainty of the evidence was very low due to the risk of bias, inconsistency, and imprecision. The meta-analysis included only a subset of studies due to concerns regarding data reporting, heterogeneity, and bias in most published research. The evidence was of very low certainty for all the review outcomes. Meta-analysis comparing changes in maximum walking distance from baseline to end of follow-up showed no improvement (MD 159.47 m, 95% CI -36.43 to 355.38; I2 = 0 %; 2 studies, 89 participants). In contrast, exercise may improve the absolute maximum walking distance at the end of follow-up compared to standard care (MD 301.89 m, 95% CI 138.13 to 465.65; I2 = 0 %; 2 studies, 108 participants). Moreover, we are very uncertain if there are differences in the changes in the six-minute walk test total distance from baseline to treatment end between exercise and standard care (MD 32.6 m, 95% CI -17.7 to 82.3; 1 study, 49 participants), and in the absolute values at the end of follow-up (MD 55.6 m, 95% CI -2.6 to 113.8; 1 study, 49 participants). Regarding pain-free walking distance, we are also very uncertain if there are differences in the mean changes in PFWD from baseline to treatment end between exercise and standard care (MD 167.41 m, 95% CI -11 to 345.83; I2 = 0%; 2 studies, 87 participants). We are very uncertain if there are differences in the absolute values of ankle-brachial index at the end of follow-up between the intervention and standard care (MD 0.01, 95% CI -0.11 to 0.12; I2 = 62%; 2 studies, 110 participants), in mortality rates at the end of follow-up (OR 0.92, 95% CI 0.42 to 2.00; I2 = 0%; 6 studies, 346 participants), health-related quality of life at the end of follow-up for the physical (MD 0.73, 95% CI -5.87 to 7.33; I2 = 64%; 2 studies, 105 participants) and mental component (MD 1.04, 95% CI -6.88 to 8.95; I2 = 70%; 2 studies, 105 participants) of the 36-item Short Form Health Survey. Finally, there may be little to no difference in reintervention rates at the end of follow-up between the intervention and standard care (OR 0.91, 95% CI 0.23 to 3.65; I2 = 65%; 5 studies, 252 participants). AUTHORS' CONCLUSIONS: There is very uncertain evidence that additional exercise therapy after successful lower limb revascularisation may improve absolute maximal walking distance at the end of follow-up compared to standard care. Evidence is also very uncertain about the effects of exercise on pain-free walking distance, six-minute walk test distance, quality of life, ankle-brachial index, mortality, and reintervention rates. Although it is not possible to confirm the effectiveness of supervised exercise compared to standard care for all outcomes, studies did not report any harm to participants from this intervention after lower limb revascularisation. Overall, the evidence incorporated into this review was very uncertain, and additional evidence is needed from large, well-designed, randomised controlled studies to more conclusively demonstrate the role additional exercise therapy has after lower limb revascularisation in people with PAD.

Early versus delayed appendicectomy for appendiceal phlegmon or abscess.

BACKGROUND: This is an update of a Cochrane review first published in 2017. Acute appendicitis (inflammation of the appendix) can be simple or complicated. Appendiceal phlegmon and appendiceal abscess are examples of complicated appendicitis. Appendiceal phlegmon is a diffuse inflammation in the bottom right of the appendix, while appendiceal abscess is a discrete inflamed mass in the abdomen that contains pus. Appendiceal phlegmon and abscess account for 2% to 10% of acute appendicitis. People with appendiceal phlegmon or abscess usually need an appendicectomy to relieve their symptoms (e.g. abdominal pain, loss of appetite, nausea, and vomiting) and avoid complications (e.g. peritonitis (infection of abdominal lining)). Surgery for people with appendiceal phlegmon or abscess may be early (immediately after hospital admission or within a few days of admission), or delayed (several weeks later in a subsequent hospital admission). The optimal timing of appendicectomy for appendiceal phlegmon or abscess is debated. OBJECTIVES: To assess the effects of early appendicectomy compared to delayed appendicectomy on overall morbidity and mortality in people with appendiceal phlegmon or abscess. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 11 June 2023, together with reference checking to identify additional studies. SELECTION CRITERIA: We included all individual and cluster-randomised controlled trials (RCTs), irrespective of language, publication status, or age of participants, comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs that randomised 828 participants to early or delayed appendicectomy for appendiceal phlegmon (7 trials) or appendiceal abscess (1 trial). The studies were conducted in the USA, India, Nepal, and Pakistan. All RCTs were at high risk of bias because of lack of blinding and lack of published protocols. They were also unclear about methods of randomisation and length of follow-up. 1. Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon We included seven trials involving 788 paediatric and adult participants with appendiceal phlegmon: 394 of the participants were randomised to the early appendicectomy group (open or laparoscopic appendicectomy as soon as the appendiceal mass resolved within the same admission), and 394 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed open or laparoscopic appendicectomy several weeks later). There was no mortality in either group. The evidence is very uncertain about the effect of early appendicectomy on overall morbidity (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.19 to 2.86; 3 trials, 146 participants; very low-certainty evidence), the proportion of participants who developed wound infections (RR 0.99, 95% CI 0.48 to 2.02; 7 trials, 788 participants), and the proportion of participants who developed faecal fistulas (RR 1.75, 95% CI 0.36 to 8.49; 5 trials, 388 participants). Early appendicectomy may reduce the abdominal abscess rate (RR 0.26, 95% CI 0.08 to 0.80; 4 trials, 626 participants; very low-certainty evidence), reduce the total length of hospital stay by about two days (mean difference (MD) -2.02 days, 95% CI -3.13 to -0.91; 5 trials, 680 participants), and increase the time away from normal activities by about five days (MD 5.00 days; 95% CI 1.52 to 8.48; 1 trial, 40 participants), but the evidence is very uncertain. 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess We included one trial involving 40 paediatric participants with appendiceal abscess: 20 were randomised to the early appendicectomy group (emergent laparoscopic appendicectomy), and 20 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed laparoscopic appendicectomy 10 weeks later). There was no mortality in either group. The trial did not report on overall morbidity, various complications, or time away from normal activities. The evidence is very uncertain about the effect of early appendicectomy on the total length of hospital stay (MD -0.20 days, 95% CI -3.54 to 3.14; very low-certainty evidence). AUTHORS' CONCLUSIONS: For the comparison of early versus delayed open or laparoscopic appendicectomy for paediatric and adult participants with appendiceal phlegmon, very low-certainty evidence suggests that early appendicectomy may reduce the abdominal abscess rate. The evidence is very uncertain whether early appendicectomy prevents overall morbidity or other complications. Early appendicectomy may reduce the total length of hospital stay and increase the time away from normal activities, but the evidence is very uncertain. For the comparison of early versus delayed laparoscopic appendicectomy for paediatric participants with appendiceal abscess, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy. Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery, and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities and length of hospital stay.

Biases and limitations in observational studies of Long COVID prevalence and risk factors: A rapid systematic umbrella review.

BACKGROUND: Observational studies form the foundation of Long COVID knowledge, however combining data from Long COVID observational studies has multiple methodological challenges. This umbrella review synthesizes estimates of Long COVID prevalence and risk factors as well as biases and limitations in the primary and review literatures. METHODS AND FINDINGS: A systematic literature search was conducted using multiple electronic databases (PubMed, EMBASE, LitCOVID) from Jan 1, 2019 until June 9, 2023. Eligible studies were systematic reviews including adult populations assessed for at least one Long COVID symptom four weeks or more after SARS-CoV-2 infection. Overall and subgroup prevalence and risk factors as well as risk of bias (ROB) assessments were extracted and descriptively analyzed. The protocol was registered with PROSPERO (CRD42023434323). Fourteen reviews of 5-196 primary studies were included: 8 reported on Long COVID prevalence, 5 on risk/protective factors, and 1 on both. Prevalence of at least 1 Long COVID symptom ranged from 21% (IQR: 8.9%-35%) to 74.5% (95% CI: 55.6%-78.0%). Risk factor reviews found significant associations between vaccination status, sex, acute COVID-19 severity, and comorbidities. Both prevalence and risk factor reviews frequently identified selection and ascertainment biases. Using the AMSTAR 2 criteria, the quality of included reviews, particularly the prevalence reviews, were concerning for the adequacy of ROB assessments and justifications for conducting meta-analysis. CONCLUSION: A high level of heterogeneity render the interpretation of pooled prevalence estimates of Long COVID challenging, further hampered by the lack of robust critical appraisals in the included reviews. Risk factor reviews were of higher quality overall and suggested consistent associations between Long COVID risk and patient characteristics.

Zinc for prevention and treatment of the common cold.

BACKGROUND: The common cold is an acute, self-limiting viral respiratory illness. Symptoms include nasal congestion and mucus discharge, sneezing, sore throat, cough, and general malaise. Given the frequency of colds, they are a public health burden and a significant cause of lost work productivity and school absenteeism. There are no established interventions to prevent colds or shorten their duration. However, zinc supplements are commonly recommended and taken for this purpose. OBJECTIVES: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS to 22 May 2023, and searched Web of Science Core Collection and two trials registries to 14 June 2023. We also used reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children or adults that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI). We excluded zinc interventions in which zinc was combined with other minerals, vitamins, or herbs (e.g. a multivitamin, or mineral supplement containing zinc). DATA COLLECTION AND ANALYSIS: We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We independently extracted data. When necessary, we contacted study authors for additional information. We assessed zinc (type and route) with placebo in the prevention and treatment of the common cold. Primary outcomes included the proportion of participants developing colds (for analyses of prevention trials only), duration of cold (measured in days from start to resolution of the cold), adverse events potentially due to zinc supplements (e.g. unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhoea), and adverse events considered to be potential complications of the common cold (e.g. respiratory bacterial infections). MAIN RESULTS: We included 34 studies (15 prevention, 19 treatment) involving 8526 participants. Twenty-two studies were conducted on adults and 12 studies were conducted on children. Most trials were conducted in the USA (n = 18), followed by India, Indonesia, Iran, and Turkey (two studies each), and Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, and the UK (one study each). The 15 prevention studies identified the condition as either common cold (n = 8) or URTI (n = 7). However, almost all therapeutic studies (17/19) focused on the common cold. Most studies (17/34) evaluated the effectiveness of zinc administered as lozenges (3 prevention; 14 treatment) in acetate, gluconate, and orotate forms; gluconate lozenges were the most common (9/17). Zinc gluconate was given at doses between 45 and 276 mg/day for between 4.5 and 21 days. Five (5/17) lozenge studies gave acetate lozenges and two (2/17) gave both acetate and gluconate lozenges. One (1/17) lozenge study administered intranasal (gluconate) and lozenge (orotate) zinc in tandem for cold treatment. Of the 17/34 studies that did not use lozenges, 1/17 gave capsules, 3/17 administered dissolved powders, 5/17 gave tablets, 4/17 used syrups, and 4/17 used intranasal administration. Most studies were at unclear or high risk of bias in at least one domain. There may be little or no reduction in the risk of developing a cold with zinc compared to placebo (risk ratio (RR) 0.93, 95% CI 0.85 to 1.01; I2 = 20%; 9 studies, 1449 participants; low-certainty evidence). There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow-up (mean difference (MD) -0.90, 95% CI -1.93 to 0.12; I2 = 96%; 2 studies, 1284 participants; low-certainty evidence). When colds occur, there is probably little or no difference in the duration of colds in days (MD -0.63, 95% CI -1.29 to 0.04; I² = 77%; 3 studies, 740 participants; moderate-certainty evidence), and there may be little or no difference in global symptom severity (standardised mean difference (SMD) 0.04, 95% CI -0.35 to 0.43; I² = 0%; 2 studies, 101 participants; low-certainty evidence). When zinc is used for cold treatment, there may be a reduction in the mean duration of the cold in days (MD -2.37, 95% CI -4.21 to -0.53; I² = 97%; 8 studies, 972 participants; low-certainty evidence), although it is uncertain whether there is a reduction in the risk of having an ongoing cold at the end of follow-up (RR 0.52, 95% CI 0.21 to 1.27; I² = 65%; 5 studies, 357 participants; very low-certainty evidence), or global symptom severity (SMD -0.03, 95% CI -0.56 to 0.50; I² = 78%; 2 studies, 261 participants; very low-certainty evidence), and there may be little or no difference in the risk of a change in global symptom severity (RR 1.02, 95% CI 0.85 to 1.23; 1 study, 114 participants; low-certainty evidence). Thirty-one studies reported non-serious adverse events (2422 participants). It is uncertain whether there is a difference in the risk of adverse events with zinc used for cold prevention (RR 1.11, 95% CI 0.84 to 1.47; I2 = 0%; 7 studies, 1517 participants; very low-certainty evidence) or an increase in the risk of serious adverse events (RR 1.67, 95% CI 0.78 to 3.57; I2 = 0%; 3 studies, 1563 participants; low-certainty evidence). There is probably an increase in the risk of non-serious adverse events when zinc is used for cold treatment (RR 1.34, 95% CI 1.15 to 1.55; I2 = 44%; 2084 participants, 16 studies; moderate-certainty evidence); no treatment study provided information on serious adverse events. No study provided clear information about adverse events considered to be potential complications of the common cold. AUTHORS' CONCLUSIONS: The findings suggest that zinc supplementation may have little or no effect on the prevention of colds but may reduce the duration of ongoing colds, with an increase in non-serious adverse events. Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold.

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

BACKGROUND: Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. SELECTION CRITERIA: We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably reduced severe intraventricular haemorrhage (grade 3 or 4) (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5885 infants; NNTB 92, 95% CI 55 to 1102; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. AUTHORS' CONCLUSIONS: The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age, and probably reduces severe intraventricular haemorrhage for infants. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.

Age- and height-dependent bias of underweight and overweight assessment standards for children and adolescents.

Background: Precision in evaluating underweight and overweight status among children and adolescents is paramount for averting health and developmental issues. Existing standards for these assessments have faced scrutiny regarding their validity. This study investigates the age and height dependencies within the international standards set by the International Obesity Task Force (IOTF), relying on body mass index (BMI), and contrasts them with Japanese standards utilizing the percentage of overweight (POW). Method: We scrutinized a comprehensive database comprising 7,863,520 children aged 5-17 years, sourced from the School Health Statistics Research initiative conducted by Japan's Ministry of Education, Culture, Sports, Science, and Technology. Employing the quantile regression method, we dissected the structure of weight-for-height distributions across different ages and sexes, quantifying the potentially biased assessments of underweight and overweight status by conventional criteria. Results: Applying IOFT criteria for underweight assessment revealed pronounced height dependence in males aged 11-13 and females aged 10-11. Notably, a discernible bias emerged, wherein children in the lower 25th percentile were classified as underweight five times more frequently than those in the upper 25th percentile. Similarly, the overweight assessment displayed robust height dependence in males aged 8-11 and females aged 7-10, with children in the lower 25th percentile for height deemed obese four or five times more frequently than their counterparts in the upper 25th percentile. Furthermore, using the Japanese POW criteria for assessment revealed significant age dependence in addition to considerably underestimating the percentage of underweight and overweight cases under the age of seven. However, the height dependence for the POW criterion was smaller than the BMI criterion, and the difference between height classes was less than 3-fold. Conclusion: Our findings underscore the intricacies of age-dependent changes in body composition during the growth process in children, emphasizing the absence of gold standards for assessing underweight and overweight. Careful judgment is crucial in cases of short or tall stature at the same age, surpassing sole reliance on conventional criteria results.

[Interpreting the evidence. Reducing subjectivity in appraising the evidence calls for a return to teaching evidence-based medicine.] / L'interpretazione delle evidenze. Per ridurre la soggettività nella lettura delle prove serve tornare a insegnare l'evidence-based medicine.

The interpretation of clinical research evidence is still characterized by wide subjectivity. This subjectivity is also visible when comparing guidelines and recommendations developed by institutions and learned societies. It is often due to bias and conflicts of interest experienced by the members of guideline panels: thus, the role of editors and publishers of journals and scientific media becomes increasingly important, and they should return to careful oversight of the content of what is published. To address the problem, however, it is necessary to return to teaching evidence-based medicine in order to restore its function as a "North star" in clinical practice and public health decision-making.

Retrospective and prospective study designs.

The labels "retrospective" and "prospective" strongly connote study quality, often favouring prospective studies. However, three definitions of these terms exist, each suggesting distinct methodological limitations. In this review, we summarize and evaluate these definitions. Caution is warranted when labeling a study "retrospective": This label should only be used when implying a risk of recall bias, which can only occur in retrospective data collection. Generally, assessing random and systematic errors is necessary to appraise study quality rather than relying on ambiguous labels.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence). AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.

Collaborative care approaches for people with severe mental illness.

BACKGROUND: Collaborative care for severe mental illness (SMI) is a community-based intervention that promotes interdisciplinary working across primary and secondary care. Collaborative care interventions aim to improve the physical and/or mental health care of individuals with SMI. This is an update of a 2013 Cochrane review, based on new searches of the literature, which includes an additional seven studies. OBJECTIVES: To assess the effectiveness of collaborative care approaches in comparison with standard care (or other non-collaborative care interventions) for people with diagnoses of SMI who are living in the community. SEARCH METHODS: We searched the Cochrane Schizophrenia Study-Based Register of Trials (10 February 2021). We searched the Cochrane Common Mental Disorders (CCMD) controlled trials register (all available years to 6 June 2016). Subsequent searches on Ovid MEDLINE, Embase and PsycINFO together with the Cochrane Central Register of Controlled Trials (with an overlap) were run on 17 December 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) where interventions described as 'collaborative care' were compared with 'standard care' for adults (18+ years) living in the community with a diagnosis of SMI. SMI was defined as schizophrenia, other types of schizophrenia-like psychosis or bipolar affective disorder. The primary outcomes of interest were: quality of life, mental state and psychiatric admissions at 12 months follow-up. DATA COLLECTION AND ANALYSIS: Pairs of authors independently extracted data. We assessed the quality and certainty of the evidence using RoB 2 (for the primary outcomes) and GRADE. We compared treatment effects between collaborative care and standard care. We divided outcomes into short-term (up to six months), medium-term (seven to 12 months) and long-term (over 12 months). For dichotomous data we calculated the risk ratio (RR) and for continuous data we calculated the standardised mean difference (SMD), with 95% confidence intervals (CIs). We used random-effects meta-analyses due to substantial levels of heterogeneity across trials. We created a summary of findings table using GRADEpro. MAIN RESULTS: Eight RCTs (1165 participants) are included in this review. Two met the criteria for type A collaborative care (intervention comprised of the four core components). The remaining six met the criteria for type B (described as collaborative care by the trialists, but not comprised of the four core components). The composition and purpose of the interventions varied across studies. For most outcomes there was low- or very low-certainty evidence. We found three studies that assessed the quality of life of participants at 12 months. Quality of life was measured using the SF-12 and the WHOQOL-BREF and the mean endpoint mental health component scores were reported at 12 months. Very low-certainty evidence did not show a difference in quality of life (mental health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.03, 95% CI -0.26 to 0.32; 3 RCTs, 227 participants). Very low-certainty evidence did not show a difference in quality of life (physical health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.08, 95% CI -0.18 to 0.33; 3 RCTs, 237 participants). Furthermore, in the medium term (at 12 months) low-certainty evidence did not show a difference between collaborative care and standard care in mental state (binary) (RR 0.99, 95% CI 0.77 to 1.28; 1 RCT, 253 participants) or in the risk of being admitted to a psychiatric hospital at 12 months (RR 5.15, 95% CI 0.67 to 39.57; 1 RCT, 253 participants). One study indicated an improvement in disability (proxy for social functioning) at 12 months in the collaborative care arm compared to usual care (RR 1.38, 95% CI 0.97 to 1.95; 1 RCT, 253 participants); we deemed this low-certainty evidence. Personal recovery and satisfaction/experience of care outcomes were not reported in any of the included studies. The data from one study indicated that the collaborative care treatment was more expensive than standard care (mean difference (MD) international dollars (Int$) 493.00, 95% CI 345.41 to 640.59) in the short term. Another study found the collaborative care intervention to be slightly less expensive at three years. AUTHORS' CONCLUSIONS: This review does not provide evidence to indicate that collaborative care is more effective than standard care in the medium term (at 12 months) in relation to our primary outcomes (quality of life, mental state and psychiatric admissions). The evidence would be improved by better reporting, higher-quality RCTs and the assessment of underlying mechanisms of collaborative care. We advise caution in utilising the information in this review to assess the effectiveness of collaborative care.

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

BACKGROUND: Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for these conditions should be removal of the source of inflammation or infection by local operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacteria. This review is the second update of the original version first published in 2014. OBJECTIVES: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults. SEARCH METHODS: We searched Cochrane Oral Health's Trials Register (26 February 2018 (discontinued)), CENTRAL (2022, Issue 10), MEDLINE Ovid (23 November 2022), Embase Ovid (23 November 2022), CINAHL EBSCO (25 November 2022) and two trials registries, and performed a grey literature search. There were no restrictions on language or date of publication. SELECTION CRITERIA: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage, or endodontic treatment) and with or without analgesics. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias. We used a fixed-effect model in the meta-analysis as there were fewer than four studies. We contacted study authors to request missing information. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: There was one new completed trial on this topic since the last update in 2018. In total, we included three trials with 134 participants. Systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess One trial (72 participants) compared the effects of a single preoperative dose of clindamycin versus a matched placebo when provided with a surgical intervention (endodontic chemo-mechanical debridement and filling) and analgesics to adults with symptomatic apical periodontitis. We assessed this study at low risk of bias. There were no differences in participant-reported pain or swelling across trial arms at any time point assessed. The median values for pain (numerical rating scale 0 to 10) were 3.0 in both groups at 24 hours (P = 0.219); 1.0 in the antibiotic group versus 2.0 in the control group at 48 hours (P = 0.242); and 0 in both groups at 72 hours and seven days (P = 0.116 and 0.673, respectively). The risk ratio of swelling when comparing preoperative antibiotic to placebo was 0.50 (95% confidence interval (CI) 0.10 to 2.56; P = 0.41). The certainty of evidence for all outcomes in this comparison was low. Two trials (62 participants) compared the effects of a seven-day course of oral phenoxymethylpenicillin (penicillin VK) versus a matched placebo when provided with a surgical intervention (total or partial endodontic chemo-mechanical debridement) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. Participants in both trials also received oral analgesics. We assessed one study at high risk of bias and the other at unclear risk of bias. There were no differences in participant-reported pain or swelling at any time point assessed. The mean difference for pain (short ordinal numerical scale 0 to 3, where 0 was no pain) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The standardised mean difference for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The certainty of evidence for all the outcomes in this comparison was very low. Adverse effects, as reported in two studies, were diarrhoea (one participant in the placebo group), fatigue and reduced energy postoperatively (one participant in the antibiotic group) and dizziness preoperatively (one participant in the antibiotic group). Systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults. AUTHORS' CONCLUSIONS: The evidence suggests that preoperative clindamycin for adults with symptomatic apical periodontitis results in little to no difference in participant-reported pain or swelling at any of the time points included in this review when provided with chemo-mechanical endodontic debridement and filling under local anaesthesia. The evidence is very uncertain about the effect of postoperative phenoxymethylpenicillin for adults with localised apical abscess or a symptomatic necrotic tooth when provided with chemo-mechanical debridement and oral analgesics. We found no studies which compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults.

Debridement for surgical wounds.

BACKGROUND: Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue may expedite wound healing. There are numerous methods of debridement available, but no consensus on which one is most effective for surgical wounds. OBJECTIVES: To assess the effects of different methods of debridement on the rate of debridement and healing of surgical wounds. SEARCH METHODS: In October 2021, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL. To identify additional studies, we searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies, reviews, meta-analyses, and health technology reports. There were no restrictions on language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with a surgical wound that required debridement, and reported time to complete wound debridement or time to wound healing, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment using the RoB 1 tool, data extraction, and GRADE assessment of the certainty of evidence. MAIN RESULTS: In this fourth update, we identified one additional study for inclusion. The review now includes six studies, with 265 participants, aged three to 91 years. Five studies were published between 1979 and 1990 and one published in 2014. The studies were carried out in hospital settings in China, Denmark, Belgium, and the UK. Six studies provided six comparisons. Due to the heterogeneity of studies, it was not appropriate to conduct meta-analyses. Four studies evaluated the effectiveness of dextranomer beads/paste; however, each study used a different comparator (Eusol-soaked dressings, 10% aqueous polyvinylpyrrolidone, 0.1% chloramine-soaked packs, and silicone foam elastomer dressing). One study compared streptokinase/streptodornase with saline-soaked dressings, and one compared endoscopic surgical debridement with conventional 'open' surgical debridement. Five studies reported time to complete debridement (reported as time to a clean wound bed) and three reported time to complete healing. One study reported effect estimates (surgical debridement via endoscopy versus surgical debridement) for time to a clean wound bed and time to complete wound healing, and it was possible to calculate effect estimates for one other study (dextranomer paste versus silicone foam elastomer) for time to complete wound healing. For the other four studies that did not report effect estimates, it was not possible to calculate time to a clean wound bed or time to complete wound healing due to missing variance and participant exclusions. None of the included studies reported outcomes pertaining to proportion of wounds completely healed, rate of reduction in wound size, rate of infection, or quality of life. All studies had unclear or high risk of bias for at least one key domain. Dextranomer paste/beads (autolytic debridement) compared with four different comparators Four studies compared dextranomer paste or beads with Eusol-soaked gauze (20 participants), 10% aqueous polyvinylpyrrolidone (40 participants), 0.1% chloramine-soaked dressings (28 participants), or silicone foam elastomer (50 participants). There is very low-certainty evidence that there may be no clear difference in time to a clean wound bed between dextranomer beads and Eusol gauze. The study did not report adverse events. There is very low-certainty evidence that there may be no difference in time to a clean wound bed between dextranomer paste and 10% aqueous polyvinylpyrrolidone gauze. There was low-certainty evidence that there may be no difference in deaths and serious adverse events. There may be a difference in time until the wounds were clinically clean and time to complete wound healing between dextranomer paste and 0.1% chloramine favouring 0.1% chloramine, but we are very uncertain. There is low-certainty evidence that there may be no difference in deaths and serious adverse events. There is very low-certainty evidence that there may be no difference in time to complete healing between dextranomer beads and silicone foam elastomer. The study did not report adverse events. Streptokinase/streptodornase solution (enzymatic) compared with saline-soaked dressings One study (21 participants) compared enzymatic debridement with saline-soaked dressings. There is low-certainty evidence that there may be no difference in time to a clean wound bed or secondary suture between streptokinase/streptodornase and saline-soaked dressings. There is very low-certainty evidence that there may be no difference in deaths and serious adverse events. Surgical debridement via endoscopic ('keyhole') surgery compared with surgical debridement by 'open' surgery (the wound is opened using a scalpel) One study (106 participants) reported time to complete wound healing and time to a clean wound bed. There is low-certainty evidence that there may be a reduction in time to complete wound healing and very low-certainty evidence that there may be no difference in time to a clean wound bed with surgical debridement via endoscopy compared to 'open' surgical debridement. The study did not report adverse events. Overall, the evidence was low to very low-certainty for all outcomes. Five included studies were published before 1991 and investigated treatments that are no longer available. Worldwide production of dextranomer products has been discontinued, except for dextranomer paste, which is currently only available in South Africa. Furthermore, Eusol, used in one study as the comparator to dextranomer, is rarely used due to risk of harmful effects on healthy tissue and the enzymatic agent streptokinase/streptodornase is no longer available worldwide. AUTHORS' CONCLUSIONS: Evidence for the effects of different methods of debridement on complete wound debridement and healing of surgical wounds remains unclear. Adequately powered, methodologically robust RCTs evaluating contemporary debridement interventions for surgical wounds are needed to guide clinical decision-making.