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Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion (UCO, n = 9) or sham occlusion (controls, n = 9), and recovered for 21 days. HI was associated with a shift to lower frequency EEG activity for the first 5 days with persisting loss of EEG power in the delta and theta bands, and initial loss of power in the alpha and beta bands in the first 14 days of recovery. In the final 3 days of recovery, there was a marked rhythmic shift towards higher frequency EEG activity after UCO. The UCO group spent less time in high-voltage sleep, and in the early evening (7:02 pm ± 47 min) abruptly stopped cycling between sleep states, with a shift to a high frequency state for 2 h 48 min ± 40 min, with tonic electromyographic activity. These findings demonstrate persisting EEG and sleep state dysmaturation after severe hypoxia-ischaemia. Loss of fetal or neonatal sleep state cycling in the early evening may be a useful biomarker for evolving cystic WMI., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Competing interests: All authors have completed the ICMJE disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: support from Cochrane for the submitted work. Certain methods studies upon which some of the recommendations are based have been carried out by authors of this guidance (GG, BNS, CH, CG, VJK, and CK). UG, BNS, and MT planned and carried out the evaluation study of the interim rapid review methods guidance.

Rapid reviews (RRs) are a helpful evidence synthesis tool to support urgent and emergent decision-making in healthcare. RRs involve abbreviating systematic review methods and are conducted in a condensed timeline to meet the decision-making needs of organisations or groups that commission them. Knowledge users (KUs) are those individuals, typically patient and public partners, healthcare providers, and policy-makers, who are likely to use evidence from research, including RRs, to make informed decisions about health policies, programmes or practices. However, research suggests that KU involvement in RRs is often limited or overlooked, and few RRs include patients as KUs. Existing RR methods guidance advocates involving KUs but lacks detailed steps on how and when to do so. This paper discusses the importance of involving KUs in RRs, including patient and public involvement to ensure RRs are fit for purpose and relevant for decision-making. Opportunities to involve KUs in planning, conduct and knowledge translation of RRs are outlined. Further, this paper describes various modes of engaging KUs during the review lifecycle; key considerations researchers should be mindful of when involving distinct KU groups; and an exemplar case study demonstrating substantive involvement of patient partners and the public in developing RRs. Although involving KUs requires time, resources and expertise, researchers should strive to balance 'rapid' with meaningful KU involvement in RRs. This paper is the first in a series led by the Cochrane Rapid Reviews Methods Group to further guide general RR methods., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper is part of a series of methodological guidance from the Cochrane Rapid Reviews Methods Group. Rapid reviews (RRs) use modified systematic review methods to accelerate the review process while maintaining systematic, transparent and reproducible methods. This paper addresses considerations for rating the certainty of evidence (COE) in RRs. We recommend the full implementation of GRADE (Grading of Recommendations, Assessment, Development and Evaluation) for Cochrane RRs if time and resources allow.If time or other resources do not permit the full implementation of GRADE, the following recommendations can be considered: (1) limit rating COE to the main intervention and comparator and limit the number of outcomes to critical benefits and harms; (2) if a literature review or a Delphi approach to rate the importance of outcomes is not feasible, rely on informal judgements of knowledge users, topic experts or team members; (3) replace independent rating of the COE by two reviewers with single-reviewer rating and verification by a second reviewer and (4) if effect estimates of a well-conducted systematic review are incorporated into an RR, use existing COE grades from such a review. We advise against changing the definition of COE or the domains considered part of the GRADE approach for RRs., Competing Interests: Competing interests: GG and EA are members of the GRADE Working Group; HJS is co-chair of the GRADE Working Group; DD works part time for Cochrane Ireland and Evidence Synthesis Ireland, which are funded within the University of Ireland Galway (Ireland) by the Health Research Board (HRB) and the Health and Social Care, Research and Development (HSC R&D) Division of the Public Health Agency in Northern Ireland., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury. KEY POINTS: Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Fetal growth restriction (FGR) is a major cause of stillbirth, prematurity and impaired neurodevelopment. Its etiology is multifactorial, but many cases are related to impaired placental development and dysfunction, with reduced nutrient and oxygen supply. The fetus has a remarkable ability to respond to hypoxic challenges and mounts protective adaptations to match growth to reduced nutrient availability. However, with progressive placental dysfunction, chronic hypoxia may progress to a level where fetus can no longer adapt, or there may be superimposed acute hypoxic events. Improving detection and effective monitoring of progression is critical for the management of complicated pregnancies to balance the risk of worsening fetal oxygen deprivation in utero , against the consequences of iatrogenic preterm birth. Current surveillance modalities include frequent fetal Doppler ultrasound, and fetal heart rate monitoring. However, nearly half of FGR cases are not detected in utero , and conventional surveillance does not prevent a high proportion of stillbirths. We review diagnostic challenges and limitations in current screening and monitoring practices and discuss potential ways to better identify FGR, and, critically, to identify the "tipping point" when a chronically hypoxic fetus is at risk of progressive acidosis and stillbirth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 King, Bennet, Stone, Clark, Gunn and Dhillon.)

Background: Health policy-makers must often make decisions in compressed time frames and with limited resources. Hence, rapid reviews have become a pragmatic alternative to comprehensive systematic reviews. However, it is important that rapid review methods remain rigorous to support good policy development and decisions. There is currently little evidence about which streamlined steps in a rapid review are less likely to introduce unacceptable levels of uncertainty while still producing a product that remains useful to policy-makers., Methods: This paper summarizes current research describing commonly used methods and practices that are used to conduct rapid reviews and presents key considerations and options to guide methodological choices for a rapid review., Results: The most important step for a rapid review is for an experienced research team to have early and ongoing engagement with the people who have requested the review. A clear research protocol, derived from a needs assessment conducted with the requester, serves to focus the review, defines the scope of the rapid review, and guides all subsequent steps. Common recommendations for rapid review methods include tailoring the literature search in terms of databases, dates, and languages. Researchers can consider using a staged search to locate high-quality systematic reviews and then subsequently published primary studies. The approaches used for study screening and selection, data extraction, and risk-of-bias assessment should be tailored to the topic, researcher experience, and available resources. Many rapid reviews use a single reviewer for study selection, risk-of-bias assessment, or data abstraction, sometimes with partial or full verification by a second reviewer. Rapid reviews usually use a descriptive synthesis method rather than quantitative meta-analysis. Use of brief report templates and standardized production methods helps to speed final report publication., Conclusions: Researchers conducting rapid reviews need to make transparent methodological choices, informed by stakeholder input, to ensure that rapid reviews meet their intended purpose. Transparency is critical because it is unclear how or how much streamlined methods can bias the conclusions of reviews. There are not yet internationally accepted standards for conducting or reporting rapid reviews. Thus, this article proposes interim guidance for researchers who are increasingly employing these methods., (© 2022. The Author(s).)

Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing of evolution of injury is vital to guide treatment. Post-HI recovery is associated with a typical neurophysiological profile, with stereotypic changes in cerebral perfusion and oxygenation. After the initial recovery, there is a delayed, prolonged reduction in cerebral perfusion related to metabolic suppression, followed by secondary deterioration with hyperperfusion and increased cerebral oxygenation, associated with altered neurovascular coupling and impaired cerebral autoregulation. These changes in cerebral perfusion are associated with the stages of evolution of injury and injury severity. Further, iatrogenic factors can also affect cerebral oxygenation during the early period of deranged metabolism, and improving clinical management may improve neuroprotection. We will review recent evidence that changes in cerebral oxygenation and metabolism after HI may be useful biomarkers of prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dhillon, Gunn, Lear, King, Lear, Wassink, Davidson, Bennet and Gunn.)

Perinatal infection/inflammation can trigger preterm birth and contribute to neurodevelopmental disability. There are currently no sensitive, specific methods to identify perinatal infection. We investigated the utility of time, frequency and non-linear measures of fetal heart rate (FHR) variability (FHRV) to identify either progressive or more rapid inflammation. Chronically instrumented preterm fetal sheep were randomly assigned to one of three different 5d continuous i.v. infusions: 1) control (saline infusions; n = 10), 2) progressive lipopolysaccharide (LPS; 200 ng/kg over 24 h, doubled every 24 h for 5d, n = 8), or 3) acute-on-chronic LPS (100 ng/kg over 24 h then 250 ng/kg/24 h for 4d plus 1 μg boluses at 48, 72, and 96 h, n = 9). Both LPS protocols triggered transient increases in multiple measures of FHRV at the onset of infusions. No FHRV or physiological changes occurred from 12 h after starting progressive LPS infusions. LPS boluses during the acute-on-chronic protocol triggered transient hypotension, tachycardia and an initial increase in multiple time and frequency domain measures of FHRV, with an asymmetric FHR pattern of predominant decelerations. Following resolution of hypotension after the second and third LPS boluses, all frequencies of FHRV became suppressed. These data suggest that FHRV may be a useful biomarker of rapid but not progressive preterm infection/inflammation., (© 2022. The Author(s).)

Background and Objectives: The number of family physicians providing maternity care continues to decline, jeopardizing access to needed care for underserved populations. Accreditation changes in 2014 provided an opportunity to create family medicine residency maternity care tracks, providing comprehensive maternity care training only for interested residents. We examined the relationship between maternity care tracks and residents' educational experiences and postgraduate practice., Methods: We included questions on maternity care tracks in an omnibus survey of family medicine residency program directors (PDs). We divided respondent programs into three categories: "Track," "No Track Needed," and "No Track." We compared these program types by their characteristics, number of resident deliveries, and number of graduates practicing maternity care., Results: The survey response rate was 40%. Of the responding PDs, 79 (32%) represented Track programs, 55 (22%) No Track Needed programs, and 94 (38%) No Track programs. Residents in a track attended more deliveries than those not in a track (at Track programs) and those at No Track Needed and No Track programs. No Track Needed programs reported the highest proportion of graduates accepting positions providing inpatient maternity care in 2019 (21%), followed by Track programs (17%) and No Track programs (5%; P<.001)., Conclusions: Where universal robust maternity care education is not feasible, maternity care tracks are an excellent alternative to provide maternity care training and produce graduates who will practice maternity care. Programs that cannot offer adequate experience to achieve competence in inpatient maternity care may consider instituting a maternity care track.

Objectives: To develop methods guidance to support the conduct of rapid reviews (RRs) produced within Cochrane and beyond, in response to requests for timely evidence syntheses for decision-making purposes including urgent health issues of high priority., Study Design and Setting: Interim recommendations were informed by a scoping review of the underlying evidence, primary methods studies conducted, and a survey sent to 119 representatives from 20 Cochrane entities, who were asked to rate and rank RR methods across stages of review conduct. Discussions among those with expertise in RR methods further informed the list of recommendations with accompanying rationales provided., Results: Based on survey results from 63 respondents (53% response rate), 26 RR methods recommendations are presented for which there was a high or moderate level of agreement or scored highest in the absence of such agreement. Where possible, how recommendations align with Cochrane methods guidance for systematic reviews is highlighted., Conclusion: The Cochrane Rapid Reviews Methods Group offers new, interim guidance to support the conduct of RRs. Because best practice is limited by the lack of currently available evidence for some RR methods shortcuts taken, this guidance will need to be updated as additional abbreviated methods are evaluated., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia ( P < 0.001), increased arterial pressure ( P < 0.001), and reduced femoral ( P < 0.005) and carotid ( P < 0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction, and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia ( P < 0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.

Progressive fetal infection/inflammation is strongly associated with neural injury after preterm birth. We aimed to test the hypotheses that progressively developing fetal inflammation leads to neuroinflammation and impaired white matter development and that the histopathological changes can be detected using high-field diffusion tensor magnetic resonance imaging (MRI). Chronically instrumented preterm fetal sheep at 0.7 of gestation were randomly assigned to receive intravenous saline (control; n = 6) or a progressive infusion of lipopolysaccharide (LPS, 200 ng intravenous over 24 h then doubled every 24 h for 5 days to induce fetal inflammation, n = 7). Sheep were killed 10 days after starting the infusions, for histology and high-field diffusion tensor MRI. Progressive LPS infusion was associated with increased circulating interleukin (IL)-6 concentrations and moderate increases in carotid artery perfusion and the frequency of electroencephalogram (EEG) activity ( p < 0.05 vs. control). In the periventricular white matter, fractional anisotropy (FA) was increased, and orientation dispersion index (ODI) was reduced ( p < 0.05 vs. control for both). Histologically, in the same brain region, LPS infusion increased microglial activation and astrocyte numbers and reduced the total number of oligodendrocytes with no change in myelination or numbers of immature/mature oligodendrocytes. Numbers of astrocytes in the periventricular white matter were correlated with increased FA and reduced ODI signal intensities. Astrocyte coherence was associated with increased FA. Moderate astrogliosis, but not loss of total oligodendrocytes, after progressive fetal inflammation can be detected with high-field diffusion tensor MRI.

Background: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) susceptibility, severity, and treatment is unclear., Purpose: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment., Data Sources: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance., Study Selection: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality., Data Extraction: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence., Data Synthesis: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19., Limitation: Half the studies were small and did not adjust for important confounding variables., Conclusion: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain., Primary Funding Source: None. (PROSPERO: registration number pending).

Before 2011, 17α-hydroxyprogesterone caproate (17P) was used to prevent recurrent preterm birth in women with singleton pregnancies and was compounded at a low cost (∼$15 per injection). In 2011, the U.S. Food and Drug Administration (FDA) approved a commercial version of 17P (trade name "Makena") through their Accelerated Approval Program, and the price of 17P subsequently increased by nearly 100-fold. This approval was largely based on a methodologically limited, placebo-controlled trial, which found that although 17P significantly reduced preterm births, the placebo group had significantly more participants with a history of preterm birth, potentially confounding the results. The FDA required a confirmatory trial for continued approval that demonstrated clinical benefit. Eight years after accelerated approval, the confirmatory trial, PROLONG (Progestin's Role in Optimizing Neonatal Gestation), found no evidence of an effect of Makena for reducing recurrent preterm birth or perinatal mortality. Trial completion triggered an automatic review of Makena by an advisory committee, which voted 9-7 to recommend revoking approval of Makena for preterm birth. Although the FDA created the Accelerated Approval Program to introduce therapies for serious conditions that lacked treatment options, Makena is an example of the limitations of this program. We encourage the FDA to re-evaluate their program and consider improvements, such as shorter timeframes to complete confirmatory trials, potentially revoking approval if the studies are not completed within a predefined timeframe, and to hold manufacturers responsible, in part, for the costs of therapy if they cannot prove a clinical benefit.

Objectives: We aimed to assess whether limiting the inclusion criteria solely to English-language publications affected the overall conclusions of evidence syntheses., Study Design and Setting: Our analyses used a dataset of a previous methods study that included 59 randomly selected Cochrane intervention reviews with no language restrictions. First, we ascertained the publication language of all 2,026 included publications. Next, we excluded studies based on the following criteria: (1) publication solely in non-English language, or (2) main publication (in case of multiple publications of the same study) in non-English language. We then re-calculated meta-analyses for outcomes that were presented in the main summary of findings tables of the Cochrane reports. If the direction of the effect estimate or the statistical significance changed, authors of the respective Cochrane reviews were consulted to assess whether the new evidence base would have changed their conclusions. The primary outcome of our analyses examined the proportion of conclusions that would change with the exclusion of non-English publications. We set the threshold for the approach as noninferior if the upper limit of the 95% confidence interval of the proportion of changed conclusions did not cross a margin of 10%., Results: Across all 59 Cochrane reviews, 29 (49%) included 80 non-English publications. For 16 (27%) of these Cochrane reviews, the exclusion of non-English publications resulted in the exclusion of at least one study. In the remaining 13 Cochrane reviews, the non-English publications were not the only or main publication of the study or they did not contribute to the main summary of the findings table, so their exclusion did not result in an exclusion of the study. Overall, the exclusion of non-English publications led to the exclusion of 31 studies contributing to 40 outcomes. For 38 of the 40 outcomes, the exclusion of non-English studies did not markedly alter the size or direction of effect estimates or statistical significance. In two outcomes, the statistical significance changed, but authors would have still drawn the same conclusion, albeit with less certainty. Thus, the proportion of changed conclusions in our sample was 0.0% (95% CI 0.0-0.6), which indicated the noninferiority of the approach. However, the majority of excluded studies were small., Conclusion: Exclusion of non-English publications from systematic reviews on clinical interventions had a minimal effect on overall conclusions and could be a viable methodological shortcut, especially for rapid reviews., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: The authors of this paper are editors of the Rapid Reviews to Strengthen Health Policy and Systems: a Practical Guide.

Background: Shared decision making (SDM) and decision aids (DAs) increase patients' involvement in health care decisions and enhance satisfaction with their choices. Studies of SDM and DAs have primarily occurred in academic centers and large health systems, but most primary care is delivered in smaller practices, and over 20% of Americans live in rural areas, where poverty, disease prevalence, and limited access to care may increase the need for SDM and DAs., Objective: To explore perceptions and practices of rural primary care clinicians regarding SDM and DAs., Design: Cross-sectional survey. Setting and Participants Primary care clinicians affiliated with the Oregon Rural Practice-based Research Network., Results: Surveys were returned by 181 of 231 eligible participants (78%); 174 could be analyzed. Two-thirds of participants were physicians, 84% practiced family medicine, and 55% were male. Sixty-five percent of respondents were unfamiliar with the term shared decision making, but following definition, 97% reported that they found the approach useful for conditions with multiple treatment options. Over 90% of clinicians perceived helping patients make decisions regarding chronic pain and health behavior change as moderate/hard in difficulty. Although 69% of respondents preferred that patients play an equal role in making decisions, they estimate that this happens only 35% of the time. Time was reported as the largest barrier to engaging in SDM (63%). Respondents were receptive to using DAs to facilitate SDM in print- (95%) or web-based formats (72%), and topic preference varied by clinician specialty and decision difficulty., Conclusions: Rural clinicians recognized the value of SDM and were receptive to using DAs in multiple formats. Integration of DAs to facilitate SDM in routine patient care may require addressing practice operation and reimbursement.

Background: Rates of labour induction are increasing. We conducted this systematic review to assess the evidence supporting use of each method of labour induction., Methods: We listed methods of labour induction then reviewed the evidence supporting each. We searched MEDLINE and the Cochrane Library between 1980 and November 2010 using multiple terms and combinations, including labor, induced/or induction of labor, prostaglandin or prostaglandins, misoprostol, Cytotec, 16,16,-dimethylprostaglandin E2 or E2, dinoprostone; Prepidil, Cervidil, Dinoprost, Carboprost or hemabate; prostin, oxytocin, misoprostol, membrane sweeping or membrane stripping, amniotomy, balloon catheter or Foley catheter, hygroscopic dilators, laminaria, dilapan, saline injection, nipple stimulation, intercourse, acupuncture, castor oil, herbs. We performed a best evidence review of the literature supporting each method. We identified 2048 abstracts and reviewed 283 full text articles. We preferentially included high quality systematic reviews or large randomised trials. Where no such studies existed, we included the best evidence available from smaller randomised or quasi-randomised trials., Results: We included 46 full text articles. We assigned a quality rating to each included article and a strength of evidence rating to each body of literature. Prostaglandin E2 (PGE2) and vaginal misoprostol were more effective than oxytocin in bringing about vaginal delivery within 24 hours but were associated with more uterine hyperstimulation. Mechanical methods reduced uterine hyperstimulation compared with PGE2 and misoprostol, but increased maternal and neonatal infectious morbidity compared with other methods. Membrane sweeping reduced post-term gestations. Most included studies were too small to evaluate risk for rare adverse outcomes., Conclusions: Research is needed to determine benefits and harms of many induction methods.

Objectives: (1) To determine the proportion of maternity care providers who continue to deliver babies in Oregon; (2) to determine the important factors relating to the decision to discontinue maternity care services; and (3) to examine how the rural liability subsidy is affecting rural maternity care providers' ability to provide maternity care services., Study Design: We surveyed all obstetrical care providers in Oregon in 2002 and 2006. Survey data, supplemented with state administrative data, were analyzed for changes in provision of maternity care, reasons for stopping maternity care, and effect of the malpractice premium subsidy on practice., Principal Findings: Only 36.6% of responding clinicians qualified to deliver babies were actually providing maternity care in Oregon in 2006, significantly lower than the proportion (47.8%) found in 2002. Cost of malpractice premiums remains the most frequently cited reason for stopping maternity care, followed by lifestyle issues. Receipt of the malpractice subsidy was not associated with continuing any maternity services., Conclusions: Oregon continues to lose maternity care providers. A state program subsidizing the liability premiums of rural maternity care providers does not appear effective at keeping rural providers delivering babies. Other policies to encourage continuation of maternity care need to be considered.

Background: Rates of labour induction are increasing., Objectives: To review the evidence supporting indications for induction., Search Strategy: We listed indications for labour induction and then reviewed the evidence. We searched MEDLINE and the Cochrane Library between 1980 and April 2008 using several terms and combinations, including induction of labour, premature rupture of membranes, post-term pregnancy, preterm prelabour rupture of membranes (PROM), multiple gestation, suspected macrosomia, diabetes, gestational diabetes mellitus, cardiac disease, fetal anomalies, systemic lupus erythematosis, oligohydramnios, alloimmunization, rhesus disease, intrahepatic cholestasis of pregnancy (IHCP), and intrauterine growth restriction (IUGR). We performed a review of the literature supporting each indication., Selection Criteria: We identified 1387 abstracts and reviewed 418 full text articles. We preferentially included high-quality systematic reviews or large randomised trials. Where no such studies existed, we included the best evidence available from smaller randomised trials and observational studies., Main Results: We included 34 full text articles. For each indication, we assigned levels of evidence and grades of recommendation based upon the GRADE system. Recommendations for induction of labour for post-term gestation, PROM at term, and premature rupture of membranes near term with pulmonary maturity are supported by the evidence. Induction for IUGR before term reduces intrauterine fetal death, but increases caesarean deliveries and neonatal deaths. Evidence is insufficient to support induction for women with insulin-requiring diabetes, twin gestation, fetal macrosomia, oligohydramnios, cholestasis of pregnancy, maternal cardiac disease and fetal gastroschisis., Authors' Conclusions: Research is needed to determine risks and benefits of induction for many commonly advocated clinical indications.

Cervical cancer and its dysplasia precursors account for significant morbidity and mortality in women worldwide. Human papillomavirus infection is common, preventable, and now widely accepted as the causative agent with oncogenic potential in the development of cervical cancer. Screening via Papanicolaou testing is critical, and interpretation of test results with knowledge of patient risk factors is imperative. Many evidence-based guidelines for screening, interpretation, and management have been developed and are widely available for use.

Venous thromboembolism is the leading cause of maternal death in the United States. Pregnancy is a risk factor for deep venous thrombosis, and risk is further increased with a personal or family history of thrombosis or thrombophilia. Screening for thrombophilia is not recommended for the general population; however, testing for inherited or acquired thrombophilic conditions is recommended when personal or family history suggests increased risk. Factor V Leiden and prothrombin G20210A mutation are the most common inherited thrombophilias, and antiphospholipid antibody syndrome is the most important acquired defect. Clinical symptoms of deep venous thrombosis may be subtle and difficult to distinguish from gestational edema. Venous compression (Doppler) ultrasonography is the diagnostic test of choice. Pulmonary embolism typically presents postpartum with dyspnea and tachypnea. Multidetector-row (spiral) computed tomography is the test of choice for pulmonary embolism. Warfarin is contraindicated during pregnancy, but is safe to use postpartum and is compatible with breastfeeding. Low-molecular-weight heparin has largely replaced unfractionated heparin for prophylaxis and treatment in pregnancy.

Background: It has been suggested that the association between birthweight and blood pressure has been overstated as a result of publication bias and, within studies, a lack of adjustment for potentially important maternal and socioeconomic confounding factors and 'overadjustment' for current body size. This study investigates the impact of potential confounding variables on the birthweight-blood pressure association in birth cohort studies from different time periods and geographical locations in Europe., Methods: Data from five European birth cohort studies (from Finland, the UK, and the Faroe Islands) taking part in the European Birth-Lifecourse-Studies (EURO-BLCS) project were analysed. Birthweight was measured at birth in all cohorts and confounding variable information was collected prospectively at subsequent follow-ups in all cohorts. Regression models were used to assess the unadjusted association between birthweight and blood pressure and then to assess the impact of potential maternal and socioeconomic confounding variables and adjustment for later body size. Analyses were carried out in the same way across all five cohorts., Results: Birthweight was consistently negatively associated with systolic blood pressure (SBP) across all cohorts. Gestational age and possibly maternal pre-pregnancy weight, but not socioeconomic status, may be important confounding factors of the relationship between birthweight and SBP. The size of the birthweight-SBP association in adulthood may be larger than in childhood before adjustment for current body size, although a cohort effect cannot be ruled out., Conclusion: This study highlights the value of future cross-cohort comparisons in the investigation of the foetal origins of adult disease.

Variation at the insulin gene (INS-)VNTR (variable number of tandem repeats) minisatellite polymorphism has been reported to be associated with both early growth and adult metabolic phenotypes. However, the samples studied have been small and the relationship between INS-VNTR variation and parameters of early growth inconsistent, with four previous studies producing conflicting results. We have studied the relationship between INS-VNTR class (measured by genotyping the nearby -23HphI variant with which it is in tight linkage disequilibrium) and early growth in 5,646 members of the Northern Finnish Birth Cohort of 1966. Comparing class III homozygotes with other genotypes using multivariate linear regression analysis, we found no significant associations with any early growth measure (birth weight, birth length, ponderal index, and head circumference at 1 year), even after stratifying subjects by growth trajectory during infancy and/or birth order. For example, among infants with limited postnatal growth realignment (n = 2,470), class III/III infants were no heavier at birth (difference [+/-SE] in the means [fully adjusted], 58 +/- 51 g; P = 0.26) than class I/- infants. No significant associations were detected following reanalysis with an additive model (for example, for birth weight, beta = 20 g [95% CI -3 to 44], P = 0.09). Studies of this large population-based cohort have failed to generate convincing evidence that INS-VNTR variation influences early growth.

Background: The diagnosis of bronchiolitis is based on typical history and results of a physical examination. The indications for and utility of diagnostic and supportive laboratory testing (eg, chest x-ray films, complete blood cell counts, and respiratory syncytial virus testing) are unclear., Objectives: To review systematically the data on diagnostic and supportive testing in the management of bronchiolitis and to assess the utility of such testing., Design: In conjunction with an expert panel, we generated admissibility criteria and derived relevant terms to search the literature published from 1980 to November 2002 in MEDLINE and the Cochrane Collaboration Database of Controlled Clinical Trials. Trained abstractors completed detailed data collection forms for each article. We summarized the data in tables after performing data integrity checks., Results: Of the 797 abstracts identified, we present evidence from 82 trials that met our inclusion criteria (17 are primary articles on diagnosis of bronchiolitis and 65are reports of treatment or prevention trials). Numerous studies demonstrate that rapid respiratory syncytial virus tests have acceptable sensitivity and specificity, but no data show that respiratory syncytial virus testing affects clinical outcomes in typical cases of the disease. Seventeen studies presented chest x-ray film data. Abnormalities on chest x-ray films ranged from 20% to 96%. Insufficient data exist to show that chest x-ray films reliably distinguish between viral and bacterial disease or predict severity of disease. Ten studies included complete blood cell counts, but most did not present specific results. In one study, white blood cell counts correlated with radiologically defined disease categories of bronchiolitis., Conclusions: A large number of studies include diagnostic and supportive testing data. However, these studies do not define clear indications for such testing or the impact of testing on relevant patient outcomes. Given the high prevalence of this disease, prospective studies of the utility of such testing are needed and feasible.

Background: Bronchiolitis is the most common lower respiratory tract infection in infants. Up to 3% of all children in their first year of life are hospitalized with bronchiolitis. Bronchodilators and corticosteroids are commonly used treatments, but little consensus exists about optimal management strategies., Objective: To conduct a systematic review of the effectiveness of commonly used treatments for bronchiolitis in infants and children., Data Sources: We searched MEDLINE and the Cochrane Controlled Trials Register for references to randomized controlled trials of bronchiolitis treatment published since 1980., Study Selection: Randomized controlled trials of interventions for bronchiolitis in infants and children were included if they were published in English between 1980 and November 2002 and had a minimum sample size of 10., Data Extraction: We abstracted data on characteristics of the study population, interventions used, and results of studies meeting entry criteria into evidence tables and analyzed them by drug category., Data Synthesis: Interventions were grouped by drug category and qualitatively synthesized., Results: Of 797 abstracts identified in the literature search, we included 54 randomized controlled trials. This review includes 44 studies of the most common interventions: epinephrine (n = 8), beta2-agonist bronchodilators (n = 13), corticosteroids (n = 13), and ribavirin (n = 10). Studies were, in general, underpowered to detect statistically significant outcome differences between study groups. Few studies collected data on outcomes that are of great importance to parents and clinicians, such as the need for and duration of hospitalization., Conclusions: Overall, little evidence supports a routine role for any of these drugs in treating patients with bronchiolitis. A sufficiently large, well-designed pragmatic trial of the commonly used interventions for bronchiolitis is needed to determine the most effective treatment strategies for managing this condition.

Purpose: Data collected from 10 institutions were reviewed to compare survival probabilities of patients with newly diagnosed brain metastases managed initially with radiosurgery (RS) alone vs. RS + whole brain radiotherapy (WBRT)., Methods and Materials: A database was created from raw data submitted from 10 institutions on patients treated with RS for brain metastases. The major exclusion criteria were resection of a brain metastasis and interval from the end of WBRT until RS >1 month (to try to ensure that the up-front intent was to combine RS + WBRT and that RS was not given for recurrent brain metastases). Survival was estimated using the Kaplan-Meier method from the date of first treatment for brain metastases until death or last follow-up. Survival times were compared for patients managed initially with RS alone vs. RS + WBRT using the Cox proportional hazards model to adjust for known prognostic factors or Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class., Results: Out of 983 patients, 31 were excluded because treatment began after 6/1/98; 159 were excluded because brain metastases were resected; 179 were excluded because there was an interval >1 month from WBRT until RS; and 45 were excluded for other reasons. Of the 569 evaluable patients, 268 had RS alone initially (24% of whom ultimately had salvage WBRT), and 301 had RS + up-front WBRT. The median survival times for patients treated with RS alone initially vs. RS + WBRT were 14.0 vs. 15.2 months for RPA Class 1 patients, 8.2 vs. 7.0 months for Class 2, and 5.3 vs. 5.5 months for Class 3, respectively. With adjustment by RPA class, there was no survival difference comparing RS alone initially to RS + up-front WBRT (p = 0.33, hazard ratio = 1.09)., Conclusions: Omission of up-front WBRT does not seem to compromise length of survival in patients treated with RS for newly diagnosed brain metastases.

Although women who experience domestic violence seek healthcare services frequently, screening and counseling rates remain low, and healthcare professionals report feeling inadequately trained to care for abused women. The English language literature from 1989 to 1999 was searched to identify and evaluate published assessments of the education of healthcare providers in domestic violence toward women. Major deficiencies in program evaluation were found. They included the use of a historical comparison group, lack of an experimental design, selection of nonstandardized outcomes without clinical performance measures, short-term follow-up, limited documentation of course content and theory, and lack of focus on the impact of programs on abused women. Educational programs generally consisted of a single session of limited duration (1-3 hours). Based on published reports, it appears that few rigorously designed evaluations have been conducted of training programs for healthcare providers in the detection and treatment of women affected by domestic violence.

Purpose: To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT)., Methods and Materials: An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone., Results: Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone., Conclusion: In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

Certified nurse-midwives and family physicians share a philosophy of family-centered maternity care. Collaboration between the two disciplines, however, has not been common. Collaboration can enhance the primary care and maternity care options available to clients of such collaborative practices. Advantages and barriers to collaboration for both types of practitioners, as well as suggestions for successful collaboration, are discussed.