Decision Aids for Decision Making about Locally Advance Breast Cancer: A Systematic Review.

Locally advanced breast cancer (LABC) is a subset of breast cancer with locoregional progression without distant metastasis. The multimodality treatment (surgery, chemotherapy, radiotherapy, hormonal and targeted therapy if required) could significantly improve results in this specific group of patients. The complex and multiple options of treatment with similar mortality rates but different outcomes depending on the patient's desires, preferences and social environment require aid to facilitate the individual patient's decisions (e.g. Decision Aids (DAs) targeting patients considering primary or adjuvant treatment in LABC). In this context, DAs have been proven fundamental to help patients and clinicians share and agree on the best value option. The current systematic review aimed to evaluate the existing DAs related to these patients with LABC and identify current status and possible improvement areas (possible scarcity and heterogeneity of instruments, the status of their development, explanation of their purpose,…). No previous systematic reviews have been published on this topic. Following Prospero registration no: CRD42021286173, studies about LABC DAs were identified, without data or language restrictions, through a systematic search of bibliographic databases in December 2021. Quality was assessed using Qualsyst criteria (range 0.0-1.0). The quality of the 17 selected studies ranged from 0.46 to 0.95. Of them, 14/17 (82%) were DAs about treatment, only one (6%) about diagnosis, and 2/17 (12%) about the employment of DAs. No screening or follow-up DAs were retrieved. Twelve (70.6%) DAs were online tools. They varied broadly regarding their characteristics and purposes. Most of the studies focused on developing and testing different DAs (5/17; 29.4%) and their impact (7/17; 41.2%). Only 4/17 (23.5%) analysed their implementation and cost. These instruments have proven to improve patient's knowledge and decision-making, decrease patient anxiety, and patients tend to undergo treatment. However, nowadays, there is still a need for further research and consensus on methodology to develop practical DAs.

Clinical practice guidelines and consensus for the screening of breast cancer: A systematic appraisal of their quality and reporting.

INTRODUCTION: Clinical practice guidelines (CPGs) and consensus statements (CSs) are being promoted to provide high-quality healthcare guidance. This systematic review has assessed the breast cancer (BC) screening CPGs and CSs quality and reporting. METHODS: A search of bibliographic databases (MEDLINE, Embase, Web of Science, Scopus and CDSR), 12 guideline databases and 51 professional society websites was performed without language restrictions from January 2017 to June 2020, following prospective registration (Prospero no.: CRD42020203807). AGREE II (% of maximum score) and RIGHT (% of total 35 items) appraised quality and reporting individually, extracting data in duplicate; reviewer agreement was 98% and 93%, respectively. RESULTS: Forty guidances with median overall quality and reporting 51% (interquartile range [IQR] 39-63) and 48% (IQR 35-65), respectively. Twenty-two (55%) and 20 (50%) did not reach the minimum standards (scores <50%). The guidances that deployed systematic reviews had better quality (74.2% vs. 46.9%; p = 0.001) and reporting (80.5% vs. 42.6%; p = 0.001). Guidances reporting a tool referral scored better (AGREE II: 72.8% vs. 43.1%, p = 0.002; RIGHT: 75.0% vs. 46.9%, p = 0.004). CONCLUSION: BC screening CPGs and CSs suffered poor quality and reporting. More than half did not reach the minimum standards. They would improve if systematic reviews were used to underpin the recommendations made.

Shared decision making in breast cancer screening guidelines: a systematic review of their quality and reporting.

BACKGROUND: Shared decision making (SDM) is a key component of evidence-based and patient-centred care. The aim of this study is to systematically review the quality of SDM proposals in clinical practice guidelines (CPGs) and consensus statements (CSs) concerning breast cancer (BC) screening. METHODS: Guidances were identified, without language restrictions, using a prospectively planned systematic search (MEDLINE, EMBASE, Web of Science, Scopus and guideline websites) from January 2010 to August 2020. Duplicate data extraction used a 31-item SDM quality assessment tool; reviewer agreement was 98%. RESULTS: SDM appeared only in 38 (49.4%) (33/68 CPGs, 4/9 CSs) documents (overall compliance with the quality tool: mean 5.74, IQR 3-8). CPGs and CSs specifically mentioning the term SDM (n = 12) had higher quality (mean 6.8, IQR 4-9 vs. mean 2.1, IQR 0-3; P = 0.001). No differences were found in mean quality comparing CPGs with CSs (3 vs. 1.6; P = 0.634), use of systematic review (4.2 vs. 2.9; P = 0.929) and publication in a journal (4 vs. 1.9; P = 0.094). Guidances with SDM were more recently reported than those without it (mean 41 vs. 57 months; P = 0.042). CONCLUSION: More than half of all the guidelines did not meet SDM quality criteria. Those that explored it were more recently reported. There is an urgent need for promoting SDM in guidances concerning BC screening issued by institutions, professional associations and medical journals.

Shared decision making in breast cancer treatment guidelines: Development of a quality assessment tool and a systematic review.

BACKGROUND: It is not clear whether clinical practice guidelines (CPGs) and consensus statements (CSs) are adequately promoting shared decision making (SDM). OBJECTIVE: To evaluate the recommendations about SDM in CPGs and CSs concerning breast cancer (BC) treatment. SEARCH STRATEGY: Following protocol registration (Prospero no.: CRD42018106643), CPGs and CSs on BC treatment were identified, without language restrictions, through systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2010 to December 2019. INCLUSION CRITERIA: CPGs and CSs on BC treatment were selected whether published in a journal or in an online document. DATA EXTRACTION AND SYNTHESIS: A 31-item SDM quality assessment tool was developed and used to extract data in duplicate. MAIN RESULTS: There were 167 relevant CPGs (139) and CSs (28); SDM was reported in only 40% of the studies. SDM was reported more often in recent publications after 2015 (42/101 (41.6 %) vs 46/66 (69.7 %), P = .0003) but less often in medical journal publications (44/101 (43.5 %) vs 17/66 (25.7 %), P = .009). In CPGs and CSs with SDM, only 8/66 (12%) met one-fifth (6 of 31) of the quality items; only 14/66 (8%) provided clear and precise SDM recommendations. DISCUSSION AND CONCLUSIONS: SDM descriptions and recommendations in CPGs and CSs concerning BC treatment need improvement. SDM was more frequently reported in CPGs and CSs in recent years, but surprisingly it was less often covered in medical journals, a feature that needs attention.

Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis.

BACKGROUND: Antenatal care of women with epilepsy is varied. The association of epilepsy and antiepileptic drug exposure with pregnancy outcomes needs to be quantified to guide management. We did a systematic review and meta-analysis to investigate the association between epilepsy and reproductive outcomes, with or without exposure to antiepileptic drugs. METHODS: We searched MEDLINE, Embase, Cochrane, AMED, and CINAHL between Jan 1, 1990, and Jan 21, 2015, with no language or regional restrictions, for observational studies of pregnant women with epilepsy, which assessed the risk of obstetric complications in the antenatal, intrapartum, or postnatal period, and any neonatal complications. We used the Newcastle-Ottawa Scale to assess the methodological quality of the included studies, risk of bias in the selection and comparability of cohorts, and outcome. We assessed the odds of maternal and fetal complications (excluding congenital malformations) by comparing pregnant women with and without epilepsy and undertook subgroup analysis based on antiepileptic drug exposure in women with epilepsy. We summarised the association as odds ratio (OR; 95% CI) using random effects meta-analysis. The PROSPERO ID of this Systematic Review's protocol is CRD42014007547. FINDINGS: Of 7050 citations identified, 38 studies from low-income and high-income countries met our inclusion criteria (39 articles including 2,837,325 pregnancies). Women with epilepsy versus those without (2,809,984 pregnancies) had increased odds of spontaneous miscarriage (OR 1·54, 95% CI 1·02-2·32; I(2)=67%), antepartum haemorrhage (1·49, 1·01-2·20; I(2)=37%), post-partum haemorrhage (1·29, 1·13-1·49; I(2)=41%), hypertensive disorders (1·37, 1·21-1·55; I(2)=23%), induction of labour (1·67, 1·31-2·11; I(2)=64%), caesarean section (1·40, 1·23-1·58; I(2)=66%), any preterm birth (<37 weeks of gestation; 1·16, 1·01-1·34; I(2)=64%), and fetal growth restriction (1·26, 1·20-1·33; I(2)=1%). The odds of early preterm birth, gestational diabetes, fetal death or stillbirth, perinatal death, or admission to neonatal intensive care unit did not differ between women with epilepsy and those without the disorder. INTERPRETATION: A small but significant association of epilepsy, exposure to antiepileptic drugs, and adverse outcomes exists in pregnancy. This increased risk should be taken into account when counselling women with epilepsy. FUNDING: EBM CONNECT Collaboration.

Graphical displays for effective reporting of evidence quality tables in research syntheses.

BACKGROUND: When generating guidelines, quality of the evidence is tabulated to capture its several domains, often using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We developed a graphic display to capture deficiencies, outliers and similarities across comparisons contained in GRADE tables. METHODS: Based on a systematic literature review capturing the effects of 32 different therapeutic comparisons on dysmenorrhoea, we synthesised evidence quality in tables and graphs. We evaluated time taken to accurately assess evident quality and preference for tables vs. graphs. RESULTS: The plots provided visually striking displays of strengths and weaknesses of the evidence across the spectrum of comparisons on a single page. Equivalent tabulated information spread over 4 pages. Participants preferred and interpreted graphs quicker and more accurately than tables. CONCLUSIONS: The graphic approach we developed makes interpreting evidence easier. Large tables are dry and cumbersome to read and assimilate. When guideline statements are accompanied by these plots, they have the scope for improving the credibility of the recommendations made, as the strength of the evidence used can be clearly seen. Further empirical research will establish the place for graphic displays.

Duration of treatment for asymptomatic bacteriuria during pregnancy.

BACKGROUND: A previous Cochrane systematic review has shown that antibiotic drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. OBJECTIVES: To assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015) and reference lists of identified articles. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 13 studies, involving 1622 women. All were comparisons of single-dose treatment with short-course (four- to seven-day) treatments. The risk of bias of trials included in this review was largely unclear, and most trials were at high risk of performance bias. The quality of the evidence was assessed using the GRADE approach. When the any antibiotic agent was used, the 'no cure' rate for asymptomatic bacteriuria in pregnant women was slightly lower for the short-course treatment over the single-dose treatment, although there was evidence of statistical heterogeneity (average risk ratio (RR) 1.28, 95% confidence interval (CI) 0.87 to 1.88; women = 1502, studies = 13; I² = 56%; very low quality evidence). Data from only good quality trials also showed better cure rates with short (four- to seven-day) regimens of the same microbial agent (average RR 1.72, 95% CI 1.27 to 2.33; women = 803, studies = two; I² = 0%; high quality evidence). There was no clear difference in the recurrence of asymptomatic bacteriuria rate between treatment and control groups, whether the same or different microbial agents were used (RR 1.13, 95% CI 0.77 to 1.66; 445 women studies = eight; I² = 0%; very low quality evidence). Differences were detected for low birthweight babies, favoring a short course (four- to seven-day treatment) of the same microbial agent, although the data come from a single trial (RR 1.65, 95% CI 1.06 to 2.57; 714 women; high quality evidence), but no differences were observed for preterm delivery (RR 1.17, 95% CI 0.77 to 1.78; women = 804; studies = three; I² = 23%; moderate quality) or pyelonephritis (RR 3.09, 95% CI 0.54 to 17.55; women = 102; studies = two; I² = 0%; very low quality evidence). Finally, single-dose treatment of any microbial agent was associated with a decrease in reports of 'any side effects' (RR 0.70, 95% CI 0.56 to 0.88; 1460 women, studies = 12; I² = 9%; low quality evidence). Evidence was downgraded for risk of bias concerns in trials contributing data and for imprecise effect estimates (wide confidence intervals crossing the line of no effect, and in some cases, small studies with few events). AUTHORS' CONCLUSIONS: A single-dose regimen of antibiotics may be less effective than a short-course (four- to seven-day) regimen, but more evidence is needed from large trials measuring important outcomes, such as cure rate. Women with asymptomatic bacteriuria in pregnancy should be treated by the standard regimen of antibiotics until more data become available testing seven-day treatment compared with shorter courses of three- or five-day regimens.

Research integrity in randomized clinical trials: A scoping umbrella review.

BACKGROUND: Randomized clinical trials (RCTs) are experiencing a crisis of confidence in their trustworthiness. Although a comprehensive literature search yielded several reviews on RCT integrity, an overarching overview is lacking. OBJECTIVES: The authors undertook a scoping umbrella review of the research integrity literature concerning RCTs. SEARCH STRATEGY AND SELECTION CRITERIA: Following prospective registration (https://osf.io/3ursn), two reviewers independently searched PubMed, Scopus, The Cochrane Library, and Google Scholar, without language or time restrictions, until November 2021. The authors included systematic reviews covering any aspect of research integrity throughout the RCT lifecycle. DATA COLLECTION AND ANALYSIS: The authors assessed methodological quality using a modified AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) tool and collated the main findings. MAIN RESULTS: A total of 55 relevant reviews, summarizing 6001 studies (median per review, 63; range, 8-1106) from 1964 to 2021, had an overall critically low quality of 96% (53 reviews). Topics covered included general aspects (15%), design and approval (22%), conduct and monitoring (11%), reporting (38%), postpublication concerns (2%), and future research (13%). The most common integrity issues covered were ethics (18%) and transparency (18%). CONCLUSIONS: Low-quality reviews identified various integrity issues across the RCT lifecycle, emphasizing the importance of high ethical standards and professionalism while highlighting gaps in the integrity landscape. Multistakeholder consensus is needed to develop specific RCT integrity standards.

Misoprostol as an adjunct to standard uterotonics for treatment of post-partum haemorrhage: a multicentre, double-blind randomised trial.

BACKGROUND: Post-partum haemorrhage is a leading cause of global maternal morbidity and mortality. Misoprostol, a prostaglandin analogue with uterotonic activity, is an attractive option for treatment because it is stable, active orally, and inexpensive. We aimed to assess the effectiveness of misoprostol as an adjunct to standard uterotonics compared with standard uterotonics alone for treatment of post-partum haemorrhage. METHODS: Women delivering vaginally who had clinically diagnosed post-partum haemorrhage due to uterine atony were enrolled from participating hospitals in Argentina, Egypt, South Africa, Thailand, and Vietnam between July, 2005, and August, 2008. Computer-generated randomisation was used to assign women to receive 600 microg misoprostol or matching placebo sublingually; both groups were also given routine injectable uterotonics. Allocation was concealed by distribution of sealed and sequentially numbered treatment packs in the order that women were enrolled. Providers and women were masked to treatment assignment. The primary outcome was blood loss of 500 mL or more within 60 min after randomisation. Analysis was by intention to treat. This study is registered, number ISRCTN34455240. FINDINGS: 1422 women were assigned to receive misoprostol (n=705) or placebo (n=717). The proportion of women with blood loss of 500 mL or more within 60 min was similar between the misoprostol group (100 [14%]) and the placebo group (100 [14%]; relative risk 1.02, 95% CI 0.79-1.32). In the first 60 min, an increased proportion of women on misoprostol versus placebo, had shivering (455/704 [65%] vs 230/717 [32%]; 2.01, 1.79-2.27) and body temperature of 38 degrees C or higher (303/704 [43%] vs 107/717 [15%]; 2.88, 2.37-2.50). INTERPRETATION: Findings from this study do not support clinical use of 600 microg sublingual misoprostol in addition to standard injectable uterotonics for treatment of post-partum haemorrhage. FUNDING: Bill & Melinda Gates Foundation, and UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Evidence summaries tailored to health policy-makers in low- and middle-income countries.

OBJECTIVE: To describe how the SUPPORT collaboration developed a short summary format for presenting the results of systematic reviews to policy-makers in low- and middle-income countries (LMICs). METHODS: We carried out 21 user tests in six countries to explore users' experiences with the summary format. We modified the summaries based on the results and checked our conclusions through 13 follow-up interviews. To solve the problems uncovered by the user testing, we also obtained advisory group feedback and conducted working group workshops. FINDINGS: Policy-makers liked a graded entry format (i.e. short summary with key messages up front). They particularly valued the section on the relevance of the summaries for LMICs, which compensated for the lack of locally-relevant detail in the original review. Some struggled to understand the text and numbers. Three issues made redesigning the summaries particularly challenging: (i) participants had a poor understanding of what a systematic review was; (ii) they expected information not found in the systematic reviews and (iii) they wanted shorter, clearer summaries. Solutions included adding information to help understand the nature of a systematic review, adding more references and making the content clearer and the document quicker to scan. CONCLUSION: Presenting evidence from systematic reviews to policy-makers in LMICs in the form of short summaries can render the information easier to assimilate and more useful, but summaries must be clear and easy to read or scan quickly. They should also explain the nature of the information provided by systematic reviews and its relevance for policy decisions.

Duration of treatment for asymptomatic bacteriuria during pregnancy.

BACKGROUND: A Cochrane systematic review has shown that drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. OBJECTIVES: To assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011) and reference lists of identified articles. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. DATA COLLECTION AND ANALYSIS: We assessed trial quality and extracted data independently. MAIN RESULTS: We included 13 studies, involving 1622 women. All were comparisons of single-dose treatment with four- to seven-day treatments. The trials were generally of limited quality. The 'no cure rate' for asymptomatic bacteriuria in pregnant women was slightly higher for the single-dose than for the short-course treatment; however, these results were not statistically significant and showed heterogeneity. When comparing the trials that used the same antibiotic in both treatment and control groups with the trials that used different antibiotics in both groups, the 'no cure rate' risk ratio was similar. There was no statistically significant difference in the recurrence of asymptomatic bacteriuria rate between treatment and control groups. Slight differences were detected for preterm births and pyelonephritis although, apart from one trial, the sample size of the trials was inadequate. Single-dose treatment was associated with a decrease in reports of 'any side-effects' . AUTHORS' CONCLUSIONS: Single-dose regimen of antibiotics may be less effective than the seven-day regimen. Women with asymptomatic bacteriuria in pregnancy should be treated by the standard regimen of antibiotics until more data become available testing seven-day compared with three- or five-day regimens.

Making GRADE accessible: a proposal for graphic display of evidence quality assessments.

When generating guidelines, quality of evidence is frequently reported in tabulated form capturing several domains, for example, study design, risk of bias and heterogeneity. Increasingly, this is done using the Grading of Recommendations Assessment, Development and Evaluation approach. As assimilating large amount of tabulated data across several comparisons and outcomes spread over many pages (sometimes hundreds) is not easy, there is a need to present evidence summaries in a more effective way. A graphic display plotting the several domains used in evidence grading on equiangular spokes starting from the same point, the data length of each spoke proportional to the magnitude of the quality, succinctly captures tabulated information. These plots allow easy identification of deficiencies, outliers and similarities in evidence quality for individual and multiple comparisons and outcomes, paving the way for their routine use alongside tabulated information.

Evaluation of the Use of Shared Decision Making in Breast Cancer: International Survey.

OBJECTIVES: To assess shared decision-making (SDM) knowledge, attitude and application among health professionals involved in breast cancer (BC) treatment. MATERIALS AND METHODS: A cross-sectional study based on an online questionnaire, sent by several professional societies to health professionals involved in BC management. There were 26 questions which combined demographic and professional data with some items measured on a Likert-type scale. RESULTS: The participation (459/541; 84.84%) and completion (443/459; 96.51%) rates were high. Participants strongly agreed or agreed in 69.57% (16/23) of their responses. The majority stated that they knew of SDM (mean 4.43 (4.36-4.55)) and were in favour of its implementation (mean 4.58 (4.51-4.64)). They highlighted that SDM practice was not adequate due to lack of resources (3.46 (3.37-3.55)) and agreed on policies that improved its implementation (3.96 (3.88-4.04)). The main advantage of SDM for participants was patient satisfaction (38%), and the main disadvantage was the patients' paucity of knowledge to understand their disease (24%). The main obstacle indicated was the lack of time and resources (40%). CONCLUSIONS: New policies must be designed for adequate training of professionals in integrating SDM in clinical practice, preparing them to use SDM with adequate resources and time provided.

Quality and reporting of clinical guidelines for breast cancer treatment: A systematic review.

BACKGROUND: High-quality, well-reported clinical practice guidelines (CPGs) and consensus statements (CSs) underpinned by systematic reviews are needed. We appraised the quality and reporting of CPGs and CSs for breast cancer (BC) treatment. METHODS: Following protocol registration (Prospero no: CRD42020164801), CPGs and CSs on BC treatment were identified, without language restrictions, through a systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2017 to June 2020. Data were extracted in duplicate assessing overall quality using AGREE II (% of maximum score) and reporting compliance using RIGHT (% of total 35 items); reviewer agreement was 98% and 96% respectively. RESULTS: There were 59 relevant guidance documents (43 CPGs, 16 CSs), of which 20 used systematic reviews for evidence synthesis. The median overall quality was 54.0% (IQR 35.9-74.3) and the median overall reporting compliance was 60.9% (IQR 44.5-84.4). The correlation between quality and reporting was 0.9. Compared to CSs, CPGs had better quality (55.4% vs 44.2%; p = 0.032) and reporting (67.18% vs 44.5%; p = 0.005). Compared to subjective methods of evidence analysis, guidance documents that used systematic reviews had better quality (76.3% vs 51.4%; p = 0.001) and reporting (87.1% vs 59.4%; p = 0.001). CONCLUSION: The quality and reporting of CPGs and CSs in BC treatment were moderately strong. Systematic reviews should be used to improve the quality and reporting of CPGs and CSs.

One-day compared with 7-day nitrofurantoin for asymptomatic bacteriuria in pregnancy: a randomized controlled trial.

OBJECTIVE: To evaluate whether a 1-day nitrofurantoin regimen is as effective as a 7-day regimen in eradicating asymptomatic bacteriuria during pregnancy. METHODS: A multicenter, double-blind, randomized, placebo controlled noninferiority trial was conducted in antenatal clinics in Thailand, the Philippines, Vietnam, and Argentina. Pregnant women seeking antenatal care between March 2004 and March 2007 who met the inclusion and exclusion criteria were invited to participate in the study. Those who consented were randomly allocated to receive either a 1-day or a 7-day course of 100 mg capsules of nitrofurantoin, which was taken twice daily. The primary outcome was bacteriologic cure on day 14 of treatment. RESULTS: : A total of 1,248 of 24,430 eligible women had asymptomatic bacteriuria, making the overall prevalence of 5.1%. Of these 1,248 women, 778 women were successfully recruited, and 386 and 392 women were randomly allocated to 1-day and 7-day regimens, respectively. Escherichia coli was the most common potentially pathogenic bacteria detected, its prevalence approaching 50%. Bacteriologic cure rates at treatment day 14 were 75.7% and 86.2% for 1-day and 7-day regimens, respectively. The cure rate difference was -10.5% (95% confidence interval -16.1% to -4.9%). Mean birth weight and mean gestational age at delivery were significantly lower in the 1-day regimen group. There were fewer adverse effects in the 1-day regimen group, but the differences were not statistically significant. CONCLUSION: A 1-day regimen of nitrofurantoin is significantly less effective than a 7-day regimen. Women with asymptomatic bacteriuria in pregnancy should receive the standard 7-day regimen. CLINICAL TRIAL REGISTRATION: ISRCTN, isrctn.org, ISRCTN11966080 LEVEL OF EVIDENCE: I.

Accuracy of diagnostic tests to detect asymptomatic bacteriuria during pregnancy.

OBJECTIVE: A dipslide is a plastic paddle coated with agar that is attached to a plastic cap that screws onto a sterile plastic vial. Our objective was to estimate the diagnostic accuracy of the dipslide culture technique to detect asymptomatic bacteriuria during pregnancy and to evaluate the accuracy of nitrate and leucocyte esterase dipslides for screening. METHODS: This was an ancillary study within a trial comparing single-day with 7-day therapy in treating asymptomatic bacteriuria. Clean-catch midstream samples were collected from pregnant women seeking routine care. Positive and negative likelihood ratios and sensitivity and specificity for the culture-based dipslide to detect and chemical dipsticks (nitrites, leukocyte esterase, or both) to screen were estimated using traditional urine culture as the "gold standard." RESULTS: : A total of 3,048 eligible pregnant women were screened. The prevalence of asymptomatic bacteriuria was 15%, with Escherichia coli the most prevalent organism. The likelihood ratio for detecting asymptomatic bacteriuria with a positive dipslide test was 225 (95% confidence interval [CI] 113-449), increasing the probability of asymptomatic bacteriuria to 98%; the likelihood ratio for a negative dipslide test was 0.02 (95% CI 0.01-0.05), reducing the probability of bacteriuria to less than 1%. The positive likelihood ratio of leukocyte esterase and nitrite dipsticks (when both or either one was positive) was 6.95 (95% CI 5.80-8.33), increasing the probability of bacteriuria to only 54%; the negative likelihood ratio was 0.50 (95% CI 0.45-0.57), reducing the probability to 8%. CONCLUSION: A pregnant woman with a positive dipslide test is very likely to have a definitive diagnosis of asymptomatic bacteriuria, whereas a negative result effectively rules out the presence of bacteriuria. Dipsticks that measure nitrites and leukocyte esterase have low sensitivity for use in screening for asymptomatic bacteriuria during gestation. CLINICAL TRIAL REGISTRATION: ISRCTN, isrctn.org, 1196608 LEVEL OF EVIDENCE: II.

Episiotomy for vaginal birth.

BACKGROUND: Episiotomy is done to prevent severe perineal tears, but its routine use has been questioned. The relative effects of midline compared with midlateral episiotomy are unclear. OBJECTIVES: The objective of this review was to assess the effects of restrictive use of episiotomy compared with routine episiotomy during vaginal birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2008). SELECTION CRITERIA: Randomized trials comparing restrictive use of episiotomy with routine use of episiotomy; restrictive use of mediolateral episiotomy versus routine mediolateral episiotomy; restrictive use of midline episiotomy versus routine midline episiotomy; and use of midline episiotomy versus mediolateral episiotomy. DATA COLLECTION AND ANALYSIS: The two review authors independently assessed trial quality and extracted the data. MAIN RESULTS: We included eight studies (5541 women). In the routine episiotomy group, 75.15% (2035/2708) of women had episiotomies, while the rate in the restrictive episiotomy group was 28.40% (776/2733). Compared with routine use, restrictive episiotomy resulted in less severe perineal trauma (relative risk (RR) 0.67, 95% confidence interval (CI) 0.49 to 0.91), less suturing (RR 0.71, 95% CI 0.61 to 0.81) and fewer healing complications (RR 0.69, 95% CI 0.56 to 0.85). Restrictive episiotomy was associated with more anterior perineal trauma (RR 1.84, 95% CI 1.61 to 2.10). There was no difference in severe vaginal/perineal trauma (RR 0.92, 95% CI 0.72 to 1.18); dyspareunia (RR 1.02, 95% CI 0.90 to 1.16); urinary incontinence (RR 0.98, 95% CI 0.79 to 1.20) or several pain measures. Results for restrictive versus routine mediolateral versus midline episiotomy were similar to the overall comparison. AUTHORS' CONCLUSIONS: Restrictive episiotomy policies appear to have a number of benefits compared to policies based on routine episiotomy. There is less posterior perineal trauma, less suturing and fewer complications, no difference for most pain measures and severe vaginal or perineal trauma, but there was an increased risk of anterior perineal trauma with restrictive episiotomy.

Mapping the theories of preeclampsia: the need for systematic reviews of mechanisms of the disease.

Preeclampsia, a major cause of morbidity in pregnancy, is still a disease of unknown cause, despite considerable research in recent times. We believe that progress in understanding the disorder would be enhanced if the systematic review methodology, similar to that used to assess data from clinical trials, is applied to studies that investigate the many theories advanced to explain its cause. This article discusses the need for and a frame work of such an endeavor. The systematic review approach helps to determine where research should be focused, to prioritize the use of resources, to understand, and then hopefully to conquer a disease that still kills mothers and infants each year, worldwide.

Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research.

BACKGROUND: Systematic reviews can serve as a tool in translation of basic life sciences research from laboratory to human research and healthcare. The extent to which reviews of animal research are systematic and unbiased is not known. METHODS: We searched, without language restrictions, Medline, Embase, bibliographies of known reviews (1996-2004) and contacted experts to identify citations of reviews of basic science literature which, as a minimum, performed search of a publicly available resource. From these we identified reviews of animal studies where laboratory variables were measured or where treatments were administered to live animals to examine their effects, and compared them with reviews of bench studies in which human or animal tissues, cell systems or organ preparations were examined in laboratories to better understand mechanisms of diseases. RESULTS: Systematic reviews of animal studies often lacked methodological features such as specification of a testable hypothesis (9/30, 30%); literature search without language restriction (8/30, 26.6%); assessment of publication bias (5/30, 16.6%), study validity (15/30, 50%) and heterogeneity (10/30, 33.3%); and meta-analysis for quantitative synthesis (12/30, 40%). Compared to reviews of bench studies, they were less prone to bias as they specified the question (96.6% vs. 80%, p = 0.04), searched multiple databases (60% vs. 26.6%, p = 0.01), assessed study quality (50% vs. 20%, p = 0.01), and explored heterogeneity (33.3% vs. 2.2%, p = 0.001) more often. CONCLUSION: There seems to be a gradient of frequency of methodological weaknesses among reviews: Attempted systematic reviews of whole animal research tend to be better than those of bench studies, though compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research.

Accuracy of Onsite Tests to Detect Asymptomatic Bacteriuria in Pregnancy: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the accuracy of onsite tests to detect asymptomatic bacteriuria among pregnant women. DATA SOURCES: We searched MEDLINE, EMBASE, Web of Science, Scopus, and Latin-American Literature from inception until June 2015 without language restrictions. The ClinicalTrials.gov register database was screened to identify any recently completed studies. METHODS OF STUDY SELECTION: Two independent reviewers selected studies that recruited asymptomatic pregnant women to evaluate the accuracy of onsite tests in detecting the presence of bacteria in the urine using urine culture as a reference standard. TABULATION, INTEGRATION, AND RESULTS: Women's characteristics, study design, urine sample collection, and handling were extracted along with the test accuracy data. Where possible, we pooled the data using a bivariate, hierarchical random-effects model. Of 1,360 screened references, 27 articles (13,641 women) with test accuracy data on nine tests met the inclusion criteria. The most commonly evaluated test was urine dipstick. The pooled sensitivity and specificity of nitrites detected by dipstick to detect asymptomatic bacteriuria were 0.55 (95% confidence interval [CI] 0.42-0.67) and 0.99 (95% CI 0.98-0.99), respectively. The Griess test to detect nitrites had a sensitivity of 0.65 (95% CI 0.50-0.78) and specificity of 0.99 (95% CI 0.98-1.00). Dipslide with Gram staining had a pooled sensitivity of 0.86 (95% CI 0.80-0.91) and specificity of 0.97 (95% CI 0.93-0.99). CONCLUSION: The specificity of onsite tests is high; however, the sensitivity is not with the result that they will fail to detect a substantial number of cases of asymptomatic bacteriuria. CLINICAL TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42015027905.