Advanced Search

Completed Systematic Reviews




Long-term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review [Entered Retrospectively]


Public Project Complete

Statistics: 59 Studies, 8 Key Questions, 1 Extraction Form,
Date Published: Mar 21, 2019 09:12AM
Description: Objective. To summarize evidence on outcomes of long-term osteoporosis drug therapy to prevent fractures, on continuing versus discontinuing osteoporosis drug therapy (i.e., placebo drug holidays), and on whether osteoporosis drug intervention effects vary as a function of patient, bone, or drug characteristics. Data sources. MEDLINE, Embase and Cochrane databases from 1995 to June 2018; ClinicalTrials.gov; bibliographies of relevant systematic reviews Review methods. Long-term osteoporosis drug therapy was defined as >3 years and drug holiday as osteoporosis drug discontinuation for ≥1 year after ≥1 year of prior osteoporosis drug use. Two reviewers independently rated risk of bias (ROB) and strength of evidence (SOE), resolving discrepancies by consensus. Included studies were English-language trials for incident fractures and harms and controlled observational studies for additional harms outcomes. For low or medium ROB studies, one reviewer extracted data and a second verified accuracy. Results. Of 56 eligible publications, 44 had low or medium ROB, including 32 publications of trials (7 unique studies) and 12 publications of observational studies (10 unique studies). Nearly all studies were comprised of postmenopausal women. Mean participant age was 72 years; all but 2 studies had a mean age <80 years. In postmenopausal women with osteoporosis, compared with placebo, 4 years of alendronate or raloxifene reduced risk of incident vertebral fractures (high SOE), 4 years of alendronate reduced risk of incident clinical fractures (moderate SOE). In postmenopausal women with past fractures, compared with placebo, both long-term estrogen and long-term estrogen/progestin reduced risk of incident clinical fractures and long-term estrogen reduced risk of incident hip fractures (all low SOE). Alendronate, denosumab and raloxifene for 4 years each significantly increased total hip and lumbar spine bone mineral density (BMD) versus placebo. Continuation versus discontinuation of alendronate after 5 years reduced risk of incident clinical vertebral fractures in one large trial (10 vs. 5 years, moderate SOE), but not in another smaller trial (7 vs. 5 years, low SOE). Continuation versus discontinuation of zoledronic acid (6 vs. 3 years) reduced risk of incident radiographic vertebral fractures (moderate SOE), but evidence was insufficient about risk of incident clinical vertebral fractures. Neither alendronate nor zoledronic acid continuation reduced risk of nonvertebral fractures (low SOE) versus discontinuation; for both, continuation was associated with generally stable hip BMD compared to small, but significant declines with discontinuation. Based primarily on observational studies, long-term bisphosphonates may increase risks of radiologically confirmed atypical femoral fractures (AFF), subtrochanteric or femoral shaft fractures without confirmed AFF features, and osteonecrosis of the jaw (ONJ). Limitations. Minimal data for men or individuals with comorbidities. Low power to assess risks of incident clinical fractures. No data compared long-term effects of sequential treatments (e.g., anabolic followed by anti-resorptive) or different durations of drug holidays. Analyses of possible treatment effect modifiers almost entirely post hoc. Observational studies used variable drug treatment and control exposures and harms definitions. Conclusions. For postmenopausal women with osteoporosis by BMD or past fractures, long-term alendronate and raloxifene reduced risk of incident vertebral fractures; long-term alendronate, estrogen, and estrogen/progestin reduced risk of clinical fractures; and long-term estrogen reduces risk of incident hip fractures. Longer-term use of bisphosphonates versus discontinuation may lower vertebral fracture risk and stabilize hip BMD, but doesn’t reduce nonvertebral fracture risk and may increase risk of AFF and ONJ. Long-term estrogen and estrogen/progestin increased risk of cardiovascular disease, and long-term estrogen increased risk of dementia and breast cancer. To address remaining knowledge gaps, future trials and observational studies should enroll diverse populations (sex, comorbidity), examine the effects of sequential treatments and compare drug holidays of different durations, be powered for clinical fractures, and use standard AFF and ONJ definitions. A priori analyses to examine whether treatment outcomes vary by patient, bone and drug treatment characteristics may inform individualized treatment decisions.
Contributor(s): Howard A. Fink, M.D., M.P.H. Roderick MacDonald, M.S. Mary L. Forte, Ph.D., D.C. Christina E. Rosebush, M.P.H. Kristine E. Ensrud, M.D., M.P.H. John T. Schousboe. M.D., Ph.D. Victoria A. Nelson, M.Sc. Kristen Ullman, M.P.H. Mary Butler, Ph.D., M.B.A. Carin M. Olson, M.D. Brent C. Taylor, M.P.H., Ph.D. Michelle Brasure, Ph.D., M.S.P.H., M.L.I.S. Timothy J. Wilt, M.D., M.P.H.
Funding Source: Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA2902015000081)
Methodology Description: None Provided

Zoom Preview | Show Downloadable Content

Fractional Exhaled Nitric Oxide Clinical Utility in Asthma Management


Public Project Complete

Statistics: 171 Studies, 1 Key Question, 1 Extraction Form,
Date Published: Mar 21, 2019 09:12AM
Description: To evaluate the clinical utility and diagnostic accuracy of fractional exhaled nitric oxide (FeNO) in people age 5 years and older with asthma; and the ability of FeNO measured at age 4 years or younger to predict a future diagnosis of asthma. PubMed ID:
Contributor(s): Zhen Wang, Ph.D., Paolo Pianosi, M.D., Karina Keogh, M.D., Feras Zaiem, M.D., Mouaz Alsawas, M.D., M.Sc., Fares Alahdab, M.D, Jehad Almasri, M.D., Khaled Mohammed, M.B.C.H, Laura Larrea Mantilla, M.D., Wigdan Farah, M.B.B.S, Lubna Daraz, Ph.D., Patricia Barrionuevo Moreno, M.D., Shalak Gunjal, M.S., Larry J. Prokop, M.L.S, M. Hassan Murad, M.D., M.P.H.
Funding Source: AHRQ
Methodology Description: We searched from databases’ inception to April 2017 for studies enrolling patients with or suspected to have asthma that evaluated the diagnosis or clinical utility of FeNO. We included randomized and nonrandomized comparative studies.

Zoom Preview | Show Downloadable Content

Management of Infertility


Public Project Complete

Statistics: 151 Studies, 7 Key Questions, 1 Extraction Form,
Date Published: Mar 21, 2019 09:12AM
Description: Objective. Previous studies have demonstrated varying success for treatment of infertility. Much of this literature however does not focus on treatment of women with specific diagnoses. This systematic review evaluated the comparative effectiveness and safety of fertility treatment strategies for (a) women of reproductive age (18-44) who are infertile due to polycystic ovary syndrome (PCOS), endometriosis, unknown reasons, or tubal or peritoneal factors or (b) couples with male factor infertility; and evaluated short- and long-term health outcomes of gamete donors in infertility. Data sources. We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for English-language studies published from January 1, 2007, to October 3, 2018, that reported live birth rates, pregnancy and neonatal outcomes, time to pregnancy, and short-term and long-term adverse outcomes for mothers and children born after infertility treatment. For male and female donors, we searched for studies reporting short- and long-term adverse effects and quality-of-life outcomes. Review methods. Two investigators screened each abstract and full-text article for inclusion; abstracted data; and performed quality ratings, applicability ratings, and evidence grading. Where appropriate, random-effects models were used to compute summary estimates of effects.
Contributor(s): Evan R. Myers, M.D., M.P.H. Jennifer L. Eaton, M.D., M.S.C.I. Kara A. McElligott, M.D., M.P.H. Patricia G. Moorman, Ph.D., M.S.P.H. Ranee Chatterjee, M.D., M.P.H. Arthurine K. Zakama, M.D. Karen Goldstein, M.D., M.S.P.H. Jennifer Strauss, Ph.D. Remy R. Coeytaux, M.D., Ph.D. Adam Goode, DPT, Ph.D. Ethan Borre, B.A. Geeta K. Swamy, M.D. Amanda J. McBroom, Ph.D. Kathryn Lallinger, M.S.L.S. Robyn Schmidt, B.A. J. Kelly Davis, B.A. Victor Hasselblad, Ph.D. Gillian D. Sanders, Ph.D.
Funding Source: Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for English-language studies published from January 1, 2007, to October 3, 2018. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects. See the review protocol (https://effectivehealthcare.ahrq.gov/topics/infertility/research-protocol) for full details.

Zoom Preview | Show Downloadable Content

Role of Bronchial Thermoplasty in Management of Asthma


Public Project Complete

Statistics: 15 Studies, 1 Key Question, 1 Extraction Form,
Date Published: Mar 21, 2019 09:12AM
Description: This review assesses the role of bronchial thermoplasty (BT) in adults with asthma.
Contributor(s): D’Anci KE, Lynch MP, Leas BF, Apter AJ, Bryant-Stephens T, Kaczmarek JL, Umscheid CA, Schoelles K.
Funding Source: AHRQ and NHLBI
Methodology Description: Data sources. We systematically searched the gray literature and five bibliographic databases, MEDLINE®, Embase®, PubMed®, CINAHL®, and the Cochrane Library, through April 20, 2017. Review methods. Eligible studies included systematic reviews, meta-analyses, randomized controlled trials (RCTs), and nonrandomized interventional studies with concurrent controls. Case reports and series were also considered for describing adverse events. Studies were evaluated for risk of bias using the Cochrane Risk of Bias instrument, and the evidence base was assessed using the methods guidance established by the Evidence-based Practice Center program.

Zoom Preview | Show Downloadable Content

Definition of Treatment-Resistant Depression in the Medicare Population


Public Project Complete

Statistics: 197 Studies, 11 Key Questions, 2 Extraction Forms,
Date Published: Mar 21, 2019 09:12AM
Description: The purpose of this technology assessment is to review the current definitions of treatment-resistant depression (TRD), to assess how closely current TRD treatment studies fit the most common definition, and to suggest how to improve TRD treatment research.
Contributor(s): Bradley N. Gaynes, M.D, M.P.H; Gary Asher, M.D, M.P.H; Gerald Gartlehner, M.D., M.P.H; Valerie Hoffman, Ph.D.; Josh Green, B.A.; Erin Boland, M.S.P.H.; Linda Lux, M.P.A.; Charlotte Randolph, B.A.; Carla Bann, Ph.D.; Emmanuel Coker-Schwimmer, M.P.H.; Meera Viswanathan, Ph.D.; Kathleen N. Lohr, Ph.D., M.Phil., M.A
Funding Source: This systematic review was proposed as a large Technology Assessment by the Centers for Medicare & Medicaid Services and conducted by the RTI-UNC Evidence-based Practice Center for the Agency for Healthcare Research and Quality.
Methodology Description: Our search for Key Questions 1-5 looked at literature published from 1/1/1995 through 4/1/2017, and our search for Key Questions 6-11 looked at literature published from 1/1/2005 through 4/1/2017. We conducted systematic literature searches for publications indexed in MEDLINE®, EMBASE, PsycINFO, and Cochrane Library. Other materials searched included consensus statements, clinical practice guidelines, and relevant government reports; website sources were Clinicaltrials.gov, Guideline.gov (AHRQ’s National Guidelines Clearinghouse), HSRProj (Health Services Research Projects in Progress database), and UpToDate®. Eligible studies for Key Questions 1-5 considered all sources noted above (including systematic reviews) except for individual intervention trials; intervention trials were only eligible for Key Questions 6-11.

Zoom Preview | Show Downloadable Content