Jeffrey C Andrews

GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength.

In the GRADE approach, the strength of a recommendation reflects the extent to which we can be confident that the composite desirable effects of a management strategy outweigh the composite undesirable effects. This article addresses GRADEs approach to determining the direction and strength of a recommendation. The GRADE describes the balance of desirable and undesirable outcomes of interest among alternative management strategies depending on four domains, namely estimates of effect for desirable and undesirable outcomes of interest, confidence in the estimates of effect, estimates of values and preferences, and resource use. Ultimately, guideline panels must use judgment in integrating these factors to make a strong or weak recommendation for or against an intervention.

Grading quality of evidence and strength of recommendations in clinical practice guidelines Part 3 of 3. The GRADE approach to developing recommendations

To cite this article: Brożek JL, Akl EA, Compalati E, Kreis J, Terracciano L, Fiocchi A, Ueffing E, Andrews J, Alonso‐Coello P, Meerpohl JJ, Lang DM, Jaeschke R, Williams JW Jr, Phillips B, Lethaby A, Bossuyt P, Glasziou P, Helfand M, Watine J, Afilalo M, Welch V, Montedori A, Abraha I, Horvath AR, Bousquet J, Guyatt GH, Schünemann HJ, for the GRADE Working Group. Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 3 of 3. The GRADE approach to developing recommendations. Allergy 2011; 66: 588–595.

Vulvodynia Interventions—Systematic Review and Evidence Grading

Introduction: State of the art guidance exists for management of vulvodynia, but the scientific basis for interventions has not been well described. Although there are many interventional therapies, and their use is increasing, there is also uncertainty or controversy about their efficacy. Objective: To systematically assess benefits and harms of interventional therapies for vulvodynia and vestibulodynia. Methods: The following databases were searched, using MeSH terms for studies related to the treatment of vulvodynia or vulva pain/pruritus/dysesthesia/hyperesthesia/hypersensitivity: MEDLINE, PsycINFO, Scopus, Cochrane Library, EBSCO Academic, and Google Scholar. Using Medical Subject Reference sections of relevant original articles, reviews, and evidence-based guidelines were screened manually. Manual searching for indirect evidence supporting interventions was done whenever no direct evidence was found for a treatment described within a review or guideline. Each modality is assessed with a grading system similar to the Grades of Recommendation, Assessment, Development, and Evaluation system. The grading system assesses study quality, effect size, benefits, risks, burdens, and costs. Results: For improvement of pain and/or function in women with vestibulodynia (provoked localized vulvodynia), there was fair evidence that vestibulectomy was of benefit, but the size of the effect cannot be determined with confidence. There was good evidence of a placebo effect from multiple studies of nonsurgical interventions. There was fair evidence of lack of efficacy for several nonsurgical interventions. There were several interventions for which there were insufficient evidence to reliably evaluate. There was insufficient evidence to judge harms or to judge long-term benefits. For clinically meaningful improvement of pain in women with generalized unprovoked vulvodynia, there was insufficient evidence for benefit of any intervention. There was fair evidence of a placebo effect in people with neuropathic pain and functional pain syndromes, from multiple studies of interventions. Based on indirect evidences from studies of patients with other pain disorders, interventions may be selected for future research. Conclusion: There is fair evidence for effectiveness of vestibulectomy for vestibulodynia; however, there is uncertainty about the size of the absolute effect, because of the risk of bias inherent in studies of pain interventions without a placebo control group. Providers and patients looking for evidence-based interventions for generalized unprovoked vulvodynia may need to rely on indirect evidences from studies of neuropathic pain and functional pain syndromes. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the obstetrician/gynecologist should be better able to identify potential causes of vulvar pain to facilitate diagnosis of vulvodynia and vestibulodynia, distinguish between the symptoms of localized, provoked vulvodynia and generalized unprovoked vulvodynia to select the most appropriate therapies, evaluate the efficacy of surgical and nonsurgical interventions for the treatment of generalized unprovoked and localized, provoked vulvodynia. In addition, assess the benefits and risks of interventional therapies for vulvodynia and vestibulodynia to improve patient care.

Nitrous Oxide for the Management of Labor Pain: A Systematic Review

BACKGROUND:We systematically reviewed evidence addressing the effectiveness of nitrous oxide for the management of labor pain, the influence of nitrous oxide on women’s satisfaction with their birth experience and labor pain management, and adverse effects associated with nitrous oxide for labor pain management. METHODS:We searched the MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for articles published in English. The study population included pregnant women in labor intending a vaginal birth, birth attendees or health care providers who may be exposed to nitrous oxide during labor, and the fetus/neonate. RESULTS:We identified a total of 58 publications, representing 59 distinct study populations: 2 studies were of good quality, 11 fair, and 46 poor. Inhalation of nitrous oxide provided less effective pain relief than epidural analgesia, but the quality of studies was predominately poor. The heterogeneous outcomes used to assess women’s satisfaction with their birth experience and labor pain management made synthesis of studies difficult. Most maternal adverse effects reported in the literature were unpleasant side effects that affect tolerability, such as nausea, vomiting, dizziness, and drowsiness. Apgar scores in newborns whose mothers used nitrous oxide were not significantly different from those of newborns whose mothers used other labor pain management methods or no analgesia. Evidence about occupational harms and exposure was limited. CONCLUSIONS:The literature addressing nitrous oxide for the management of labor pain includes few studies of good or fair quality. Further research is needed across all of the areas examined: effectiveness, satisfaction, and adverse effects.

Progestogens for Preterm Birth Prevention A Systematic Review and Meta-Analysis

OBJECTIVE: We systematically reviewed the effectiveness of progestogens for prevention of preterm birth among women with prior spontaneous preterm birth, multiple gestations, preterm labor, short cervix, or other indications. DATA SOURCES: We searched MEDLINE and EMBASE databases for English language articles published from January 1966 to October 2011. METHODS OF STUDY SELECTION: We excluded publications that were not randomized controlled trials or had fewer than 20 participants, identifying 34 publications, of which 19 contained data for Bayesian meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted data and assigned overall quality ratings based on predetermined criteria. Among women with prior preterm birth and a singleton pregnancy (five randomized controlled trials), progestogen treatment decreased the median risk of preterm birth by 22% (relative risk [RR] 0.78, 95% Bayesian credible interval 0.68–0.88) and neonatal death by 42% (RR 0.58, 95% Bayesian credible interval 0.27–0.98). The evidence suggests progestogen treatment does not prevent prematurity (RR 1.02, 95% Bayesian credible interval 0.87–1.17) or neonatal death (RR 1.44, 95% Bayesian credible interval 0.46–3.18) in multiple gestations. Limited evidence suggests progestogen treatment may prevent prematurity in women with preterm labor (RR 0.62, 95% Bayesian credible interval 0.47–0.79) and short cervix (RR 0.52, 95% Bayesian credible interval 0.36–0.70). Across indications, evidence about maternal, fetal, or neonatal health outcomes, other than reducing preterm birth and neonatal mortality, is inconsistent, insufficient, or absent. CONCLUSION: Progestogens prevent preterm birth when used in singleton pregnancies for women with a prior preterm birth. In contrast, evidence suggests lack of effectiveness for multiple gestations. Evidence supporting all other uses is insufficient to guide clinical care. Overall, clinicians and patients lack longer-term information to understand whether intervention has the ultimately desired outcome of preventing morbidity and promoting normal childhood development.

Systematic review of therapies for noncyclic chronic pelvic pain in women.

Abstract We synthesized the literature (articles published between 1990 and May 2011) on the treatment of noncyclic and mixed cyclic/noncyclic chronic pelvic pain (CPP) in adult women. Two reviewers assessed studies against predetermined inclusion/exclusion criteria, extracted data regarding participant and intervention characteristics and outcomes, and assigned overall quality and strength of evidence ratings. Of 2081 studies, 21 addressed surgical or nonsurgical interventions. Definitions of CPP and participant characteristics varied across studies, and most studies were of poor quality, which precluded data synthesis. Although surgical and nonsurgical approaches both improved pain, neither was more effective when directly compared in 3 studies. Laparoscopic adhesiolysis or laparoscopic uterosacral nerve ablation did not further improve pain scores over diagnostic laparoscopy. The evidence to conclude that surgical intervention is either effective or ineffective or that one technique is superior to another is insufficient. Most studies on nonsurgical approaches evaluated hormonal therapies in endometriosis-associated CPP and were not placebo controlled. Few studies addressed nonhormonal or nonpharmacologic approaches. Harms reporting was limited. Overall, no nonsurgical treatment was more or less effective than another, except for the clear negative effect of raloxifene. In general, the literature addressing therapies for CPP in women is of poor quality and inconclusive. Improved characterizations of the targeted condition and interventions in CPP research, including a uniform definition and standardized evaluation, are necessary to inform treatment choices. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to assess the effects of surgical and nonsurgical interventions on the outcomes of pain status, functional status, satisfaction with care, and quality of life; to evaluate the effectiveness of interventions for noncyclic chronic pelvic pain; and to categorize areas of future research need.

Procedures and Uterine-Sparing Surgeries for Managing Postpartum Hemorrhage: A Systematic Review.

Importance Postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality and morbidity worldwide. Objective The aim of this study was to systematically review literature on procedures (eg, uterine artery embolization) and uterine-sparing surgeries for PPH. Evidence Acquisition We searched MEDLINE and other databases from 1990 to November 2014. Two reviewers independently evaluated studies against predetermined criteria, extracted data, and assessed study quality and strength of the evidence (confidence in the effect). Results Twenty-eight small studies addressed 1 or more procedures (19 studies of embolization, 5 of uterine tamponade) or surgeries (5 studies of arterial ligation, 5 of uterine compression sutures). Studies primarily evaluated bleeding control and adverse effects. Rates of hemostasis were typically greater than 60% in studies reporting such data after failure of conservative management. Postprocedure infertility occurred in 0% to 43% of women in a small number of studies that reported these data. Uterine tamponade successfully controlled bleeding in more than 50% of women, with few harms reported. Success rates for ligation and sutures ranged from 36% to 96%; harms included surgical injury, infection, and fertility-associated effects. Conclusions and Relevance A limited body of evidence addresses these interventions for PPH. Median rates of hemostasis ranged from 36% to 98%; however, these data come from few studies with less than 2100 total participants. Harms were not well characterized. Some studies with longer-term follow-up reported infertility in women undergoing embolization. Few adverse events with tamponade, ligation, or sutures were reported. Given the insufficient evidence, clinicians must continue to make individual care decisions based on each woman’s clinical situation and available management options. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to understand the effects of procedures and uterine-sparing surgeries for PPH on control of bleeding and adverse effects including infertility and adverse pregnancy outcomes; understand the issues in defining and diagnosing PPH; and understand the areas of future research need.

Pharmacologic Agents That Promote Airway Clearance in Hospitalized Subjects: A Systematic Review

Pharmacologic agents to promote mucus clearance may reduce the sequelae of obstructive secretions. We systematically reviewed comparative studies of pharmacologic agents for mucus clearance in hospitalized or postoperative subjects without cystic fibrosis and over 12 months of age. We searched MEDLINE and other databases from January 1970 to July 2014 to identify relevant literature. Two reviewers independently assessed each study against predetermined inclusion/exclusion criteria. Two reviewers also independently extracted data regarding subject and intervention characteristics and outcomes and assigned overall quality ratings. The 9 studies meeting review criteria included 5 randomized controlled trials, 3 crossover randomized controlled trials, and one retrospective cohort study. Studies were small and together included a total of 379 subjects (mean of 42 subjects per study). N-acetylcysteine, heparin plus N-acetylcysteine, albuterol, ipratropium bromide, and saline were assessed. Studies reported no benefit of studied agents on expectoration, pulmonary function, and atelectasis and little effect on changes in sputum volume, weight, or viscosity. Adverse effects of agents were not consistently reported. Nausea was reported in 2 studies of N-acetylcysteine (one paper reported 2 experiments and did not clearly identify in which experiment adverse effects occurred), 3 studies reported that there were no adverse events, and 3 studies did not address adverse effects at all. Further research with clearly characterized populations and interventions is needed to understand the potential benefits and adverse effects of mucoactive agents.

Hormonal contraceptives with ethinyl estradiol were associated with increased thrombotic stroke and MI

QUESTION Are hormonal contraceptives associated with increased risk for thrombotic stroke or myocardial infarction (MI)? METHODS DESIGN Population-based cohort study with linkage of 4 national registries between 1995 and 2009. SETTING Denmark. PARTICIPANTS 1 626 158 women 15 to 49 years of age. Exclusion criteria included past venous or arterial thrombotic event; past gynecologic breast lung abdominal or hematologic cancer; or past hysterectomy sterilization bilateral oophorectomy or 2 unilateral oophorectomies. Data were censored during pregnancies. RISK FACTORS Filled prescriptions for hormonal contraceptives. Analyses were adjusted for age; education (level and duration); calendar year; and use of medications for hypertension heart disease diabetes and hyperlipidemia. OUTCOMES Thrombotic stroke and MI identified through diagnostic codes in the National Registry of Patients and the Register of Causes of Death. MAIN RESULTS 3311 (0.2%) women had a thrombotic stroke and 1725 (0.1%) had an MI during 14 251 063 woman-years of follow-up. Thrombotic stroke. Incidence in nonusers was 24 per 100 000 woman-years (2260 events). Levonorgestrel intrauterine devices (IUDs) were associated with reduced risk (adjusted relative risk [aRR] 0.73 95% CI 0.54 to 0.98); progestin-only pills or implants were not associated with increased risk (aRR range 0.44 to 1.4). Two of three 20-microg ethinyl estradiol formulations six of seven 30- to 40-microg formulations and one of two 50-microg formulations were associated with increased risk (aRR range 1.5 to 2.3) (Table). The vaginal ring was associated with increased risk (aRR 2.5 CI 1.4 to 4.4). MI. Incidence in nonusers was 13 per 100 000 woman-years (1228 events). Progestin-only interventions were not associated with increased risk (aRR range 0 to 2.1). One 20-microg ethinyl estradiol formulation five 30- to 40-microg formulations and both 50-microg formulations were associated with increased risk (aRR range 1.6 to 4.3) (Table). The vaginal ring was not associated with increased risk. Data were insufficient to evaluate hormonal contraceptives given in a patch. CONCLUSION Oral hormonal contraceptives containing ethinyl estradiol were associated with increased risk for thrombotic stroke and myocardial infarction.Association between prescription for hormonal contraceptives and thrombotic stroke or MI*OutcomesHormonal contraceptivesRRdagger (95% CI)Thrombotic strokeEthinyl estradiol 20 microg plus progestindouble dagger1.6 (1.4 to 1.9)Ethinyl estradiol 30 to 40 microg plus progestin section sign1.8 (1.6 to 1.9)Ethinyl estradiol 50 microg plus progestin||2.0 (1.5 to 2.7)MIEthinyl estradiol 20 microg plus progestindouble dagger1.4 (1.1 to 1.8)Ethinyl estradiol 30 to 40 microg plus progestin section sign1.9 (1.7 to 2.1)Ethinyl estradiol 50 microg plus progestin||3.7 (2.8 to 5.0)*MI = myocardial infarction; RR = risk ratio; CI defined in Glossary.daggerAdjusted for progestin type age and calendar year. Risk > 1.0 indicates increased risk associated with hormonal contraceptive use. P = 0.24 for dose trend in thrombotic stroke; P < 0.001 for dose trend in MI.double daggerProgestin = desogestrel gestodene or drospirenone. section signProgestin = norethindrone levonorgestrel norgestimate desogestrel gestodene drospirenone or cyproterone acetate.||Progestin = norethindrone or levonorgestrel.

Cervix Cancer Screening Guideline Judgments Are Not Explicit and Transparent

To the Editor The new screening guidelines for the “prevention and early detection of cervical cancer” were jointly published by the American Cancer Society, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP) in the American Journal of Clinical Pathology , CA: A Cancer Journal for Clinicians , and the Journal of Lower Genital Tract Disease on March 14, 2012.1 I am asking for more transparency and more explicit disclosure of the judgments about risk and harm thresholds and trade-offs. The guideline panels used the GRADE (Grading Recommendations Assessment, Development, and Evaluation) system to provide a framework for the guideline development process. An integral aspect of the GRADE process is that the grading of the recommendations must be explicit, and that the judgments made by the panels to determine the balance between benefits and risks be explicit and not hidden. I appreciate that there are supplemental materials, including the work of the subgroups that you have made available online.2 I also appreciate that most professionals will not have time to read the entire guideline article, much less the supplemental materials, and that patients and stakeholders will likely not access these materials. The guideline publication explains the difference between strong and weak recommendations, acknowledges that both types were included in the document, but does not stipulate which recommendations were strong and which were …