Recently Published Projects

Published on June 27, 2021
Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-Analysis
0 Studies • 2 Key Questions • 0 Extraction Forms
Project created on June 27, 2021
Last updated on June 27, 2021
Objectives: Objectives. To evaluate the effectiveness and comparative effectiveness of pharmacologic and non-pharmacologic therapies for the acute treatment of episodic migraine in adults. Data source. MEDLINE, Embase, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Scopus and various grey literature sources from database inception to April 24, 2020. Comparative effectiveness evidence about triptans and nonsteroidal anti-inflammatory drugs (NSAIDs) were extracted from existing systematic reviews. Review methods. We included randomized controlled trials (RCTs) and comparative observational studies that enrolled adults who received an intervention to acutely treat episodic migraine. Pairs of independent reviewers selected and appraised studies. Results. Data on triptans were derived from 186 RCTs summarized in 9 systematic reviews (101,276 patients, most studied was sumatriptan, followed by zolmitriptan, eletriptan, naratriptan, almotriptan, rizatriptan, and frovatriptan). Compared with placebo, triptans resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (high strength of the body of evidence [SOE]). Data on NSAIDs were derived from 5 systematic reviews (13,214 patients, most studied was ibuprofen, followed by diclofenac and ketorolac). Compared with placebo, NSAIDs probably resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (moderate SOE). For other interventions, we included 135 RCTs and 6 comparative observational studies (37,653patients). Compared with placebo, antiemetics (low SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE) and acetaminophen (moderate SOE) reduced acute pain. Opioids were evaluated in 15 studies (2,208 patients). Tramadol in combination with acetaminophen, butorphanol, meperidine, morphine and hydromorphone may reduce pain at 2 hours and 1 day, compared with placebo (low SOE). Some opioids may be less effective than some antiemetics or dexamethasone (low SOE). No studies evaluated instruments for predicting risk of opioid misuse, opioid use disorder or overdose, or evaluated risk mitigation strategies to be used when prescribing opioids for the acute treatment of episodic migraine. Calcitonin gene-related peptide (CGRP) receptor antagonists improved headache relief at 2 hours and increased the likelihood of being headache-free at 2 hours, at 1 day, and at 1 week (low to high SOE). Lasmiditan (the first approved 5-HT1F receptor agonist) restored function at 2 hours and resolved pain at 2 hours, 1 day, and 1 week (moderate to high SOE). Sparse and low SOE suggested possible effectiveness of dexamethasone, dipyrone, flunarazine, magnesium sulfate, octreotide, tezampanel, and tonabersat. Compared with placebo, several non-pharmacologic treatments may improve various measures of pain, including remote electrical neuromodulation (moderate SOE), magnetic stimulation (low SOE), acupuncture (low SOE), chamomile oil (low SOE), external trigeminal nerve stimulation (low SOE), and eye movement desensitization re-processing (low SOE). However, these interventions, including the noninvasive neuromodulation devices, have only been evaluated by single or very few trials. Conclusions. A number of acute treatments for episodic migraine exist with varying degrees of evidence for effectiveness and harms. Use of triptans, NSAIDs, antiemetics, dihydroergotamine, CGRP antagonists, and lasmiditan is associated with improved pain and function. The evidence base for many other interventions for acute treatment, including opioids, remains limited.
Published on June 27, 2021
Cervical Ripening in the Outpatient Setting
40 Studies • 4 Key Questions • 40 Extraction Forms
Project created on June 27, 2021
Last updated on June 27, 2021
Objectives: Structured Abstract Objectives. To assess the comparative effectiveness and potential harms of cervical ripening in the outpatient setting (vs. inpatient, vs. other outpatient intervention) and of fetal surveillance when a prostaglandin is used for cervical ripening. Data sources. Electronic databases (Ovid® MEDLINE®, Embase®, CINAHL®, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) to July 2020; reference lists; and a Federal Register notice. Review methods. Using predefined criteria and dual review, we selected randomized controlled trials (RCTs) and cohort studies of cervical ripening comparing prostaglandins and mechanical methods in outpatient versus inpatient settings; one outpatient method versus another (including placebo or expectant management); and different methods/protocols for fetal surveillance in cervical ripening using prostaglandins. When data from similar study designs, populations, and outcomes were available, random effects using profile likelihood meta-analyses were conducted. Inconsistency (using I2) and small sample size bias (publication bias, if ≥10 studies) were assessed. Strength of evidence (SOE) was assessed. All review methods followed Agency for Healthcare Research and Quality Evidence-based Practice Center methods guidance. Results. We included 30 RCTs and 10 cohort studies (73% fair quality) involving 9,618 women. The evidence is most applicable to women aged 25 to 30 years with singleton, vertex presentation and low-risk pregnancies. No studies on fetal surveillance were found. The frequency of cesarean delivery (2 RCTs, 4 cohort studies) or suspected neonatal sepsis (2 RCTs) was not significantly different using outpatient versus inpatient dinoprostone for cervical ripening (SOE: low). In comparisons of outpatient versus inpatient single-balloon catheters (3 RCTs, 2 cohort studies), differences between groups on cesarean delivery, birth trauma (e.g., cephalohematoma), and uterine infection were small and not statistically significant (SOE: low), and while shoulder dystocia occurred less frequently in the outpatient group (1 RCT; 3% vs. 11%), the difference was not statistically significant (SOE: low). In comparing outpatient catheters and inpatient dinoprostone (1 double-balloon and 1 single-balloon RCT), the difference between groups for both cesarean delivery and postpartum hemorrhage was small and not statistically significant (SOE: low). Evidence on other outcomes in these comparisons and for misoprostol, double-balloon catheters, and hygroscopic dilators was insufficient to draw conclusions. In head to head comparisons in the outpatient setting, the frequency of cesarean delivery was not significantly different between 2.5 mg and 5 mg dinoprostone gel, or latex and silicone single-balloon catheters (1 RCT each, SOE: low). Differences between prostaglandins and placebo for cervical ripening were small and not significantly different for cesarean delivery (12 RCTs), shoulder dystocia (3 RCTs), or uterine infection (7 RCTs) (SOE: low). These findings did not change according to the specific prostaglandin, route of administration, study quality, or gestational age. Small, nonsignificant differences in the frequency of cesarean delivery (6 RCTs) and uterine infection (3 RCTs) were also found between dinoprostone and either membrane sweeping or expectant management (SOE: low). These findings did not change according to the specific prostaglandin or study quality. Evidence on other comparisons (e.g., single-balloon catheter vs. dinoprostone) or other outcomes was insufficient. For all comparisons, there was insufficient evidence on other important outcomes such as perinatal mortality and time from admission to vaginal birth. Limitations of the evidence include the quantity, quality, and sample sizes of trials for specific interventions, particularly rare harm outcomes. Conclusions. In women with low-risk pregnancies, the risk of cesarean delivery and fetal, neonatal, or maternal harms using either dinoprostone or single-balloon catheters was not significantly different for cervical ripening in the outpatient versus inpatient setting, and similar when compared with placebo, expectant management, or membrane sweeping in the outpatient setting. This evidence is low strength, and future studies are needed to confirm these findings.
Published on June 27, 2021
Integrating Palliative Care in Ambulatory Care of Non-Cancer Serious Chronic Illness
39 Studies • 30 Key Questions • 39 Extraction Forms
Project created on June 27, 2021
Last updated on June 27, 2021
Objectives: Objectives. To evaluate availability, effectiveness, and implementation of interventions for integrating palliative care into ambulatory care for U.S.-based adults with serious life-threatening chronic illness or conditions other than cancer and their caregivers We evaluated interventions addressing identification of patients, patient and caregiver education, shared decision-making tools, clinician education, and models of care. Data sources. We searched key U.S. national websites (March 2020) and PubMed®, CINAHL, and the Cochrane Central Register of Controlled Trials (through May 2020). We also engaged Key Informants. Review methods. We completed a mixed-methods review; we sought, synthesized, and integrated Web resources; quantitative, qualitative and mixed-methods studies; and input from patient/caregiver and clinician/stakeholder Key Informants. Two reviewers screened websites and search results, abstracted data, assessed risk of bias or study quality, and graded strength of evidence (SOE) for key outcomes: health-related quality of life, patient overall symptom burden, patient depressive symptom scores, patient and caregiver satisfaction, and advance directive documentation. We performed meta-analyses when appropriate. Results. We included 46 Web resources, 20 quantitative effectiveness studies, and 16 qualitative implementation studies across primary care and specialty populations. Various prediction models, tools, and triggers to identify patients are available, but none were evaluated for effectiveness or implementation. Numerous patient and caregiver education tools are available, but none were evaluated for effectiveness or implementation. All of the shared decision-making tools addressed advance care planning; these tools may increase patient satisfaction and advance directive documentation compared with usual care (SOE: Low). Patients and caregivers prefer advance care planning discussions grounded in patient and caregiver experiences with individualized timing. Although numerous education and training resources for non-palliative care clinicians are available, we were unable to draw conclusions about implementation, and none have been evaluated for effectiveness. Models for integrating palliative care were not more effective than usual care for improving health-related quality of life or patient depressive symptom scores (SOE: Moderate) and may have little to no effect on increasing patient satisfaction or decreasing overall symptom burden (SOE: Low), but models for integrating palliative care were effective for increasing advance directive documentation (SOE: Moderate). Multimodal interventions may have little to no effect on increasing advance directive documentation (SOE: Low) and other graded outcomes were not assessed. For utilization, models for integrating palliative care were not more effective than usual care for decreasing hospitalizations; we were unable to draw conclusions about most other aspects of utilization or cost and resource use. We were unable to draw conclusions about caregiver satisfaction or specific characteristics of models for integrating palliative care. Patient preferences for appropriate timing of palliative care varied; costs, additional visits, and travel were seen as barriers to implementation. Conclusions. For integrating palliative care into ambulatory care for serious illness and conditions other than cancer, advance care planning shared decision-making tools and palliative care models were the most widely evaluated interventions and may be effective for improving only a few outcomes. More research is needed particularly on identification of patients for these interventions; education for patients, caregivers, and clinicians; shared decision-making tools beyond advance care planning and advance directive completion; and specific components, characteristics, and implementation factors in models for integrating palliative care.
Published on June 27, 2021
Care Interventions for People Living With Dementia (PLWD) and Their Caregivers [Entered Retrospectively]
634 Studies • 1 Key Questions • 634 Extraction Forms
Project created on June 27, 2021
Last updated on June 27, 2021
Objectives: Structured Abstract Objective. To understand the evidence base for care interventions for people living with dementia (PLWD) and their caregivers, and to assess the potential for broad dissemination and implementation of that evidence. Data sources. We searched Ovid Medline, Ovid Embase, Ovid PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials, nonrandomized controlled trials, and quasi-experimental designs published and indexed in bibliographic databases through March, 2020. Review methods. We searched for nondrug interventions targeting PLWD, their informal or formal caregivers, or health systems. Two investigators screened abstracts and full-text articles of identified references for eligibility. Eligible studies included randomized controlled trials and quasi-experimental observational studies enrolling people with Alzheimer’s disease or related dementias or their informal or formal caregivers. We extracted basic study information from all eligible studies. We assessed risk of bias, and summarized results for studies not judged to be NIH Stage Model 0 to 2 (pilot or small sample size studies) or to have high risk of bias. We grouped interventions into categories based on intervention target. Results. We identified 9217 unique references, of which 627 unique studies with an additional 267 companion articles were eligible. We classified interventions into 37 major categories. With few exceptions, we did not combine data quantitatively due to variability of interventions, comparison groups, outcomes measured, and study timing. Low-strength evidence shows that an intensive multicomponent intervention for informal caregiver support, with education, group discussion, in-home and phone support, and caregiver feedback (i.e. discrete adaptations of REACH II), may improve informal caregiver depression at 6 months. Low-strength evidence also shows that collaborative care models (i.e. Care Ecosystems or discrete adaptations of the ACCESS models) may improve quality of life for PLWD and health system-level markers, including improvements in guideline-based quality indicators and reducing emergency room visits. The literature does not allow for further determination of whether the very small to small average effects in quality of life applied to all enrolled PLWD or if larger effects were concentrated in an unidentified subgroup. For all other interventions and outcomes, we found the evidence insufficient to draw conclusions. Insufficient evidence does not mean that the intervention is determined to be of no value to PLWD or their caregivers. Rather, it means that due to the uncertainty of the evidence, we could not draw meaningful conclusions at this time. Conclusions. Despite hundreds of studies, very little evidence supports widespread dissemination of any general care approaches for PLWD or caregivers. This review demonstrates the need for larger, longer-term, and more rigorous studies of interventions.
Published on June 27, 2021
Therapies for Clinically Localized Prostate Cancer [Entered Retrospectively]
67 Studies • 1 Key Questions • 67 Extraction Forms
Project created on June 27, 2021
Last updated on June 27, 2021
Objectives: Structured Abstract Objective. To identify new information that updates findings from previous AHRQ and AUA funded reviews evaluating therapies for clinically localized prostate cancer (CLPC). Sources. Bibliographic databases (2013-January 2020); ClinicalTrials.gov; systematic reviews Methods. Controlled studies of CLPC (T1-T3a) treatments with duration ≥5 years for mortality and metastases and ≥1 year for quality of life and harms. Interventions included watchful waiting (WW), active surveillance or monitoring (AS, AM), androgen deprivation (AD), focal and whole gland therapies or combinations. We evaluated how patient and tumor characteristics modify treatment outcomes and how provider/hospital characteristics modify effectiveness of radical prostatectomy (RP) compared to other therapies. One investigator rated risk of bias (ROB), extracted data, and assessed certainty of evidence; a second checked accuracy. We analyzed English-language studies with low or medium ROB. We incorporated findings from RCTs identified in the 2014 AHRQ and 2016 AUA funded reviews if new RCTs provided information on the same intervention comparison. We derived thresholds defining “small”, “moderate” and “large” effect, summarize key findings from prior reviews and the impact of new research. Results. We identified 67 eligible references; 17 unique RCTs. Among clinically, rather than PSA detected CLPC, WW may increase overall and prostate-cancer mortality, and metastases versus RP at 20+ years. Urinary and erectile dysfunction were lower with WW versus RP. WW‘s effect on mortality may have varied by tumor risk and age but not by race, health status, comorbidities or PSA. AM probably results in little to no difference in overall or prostate-cancer mortality in PSA detected CLPC versus RP or EBR plus AD through 10 years regardless of tumor risk. Metastases were infrequent but slightly higher with AM. Harms were greater with RP than AM and mixed between EBR plus AD versus AM. 3D-Conformal EBR and AD plus low-dose-rate brachytherapy (BT) provided a small reduction in all-cause mortality versus 3D-CRT and AD but little to no difference on metastases. EBR plus AD versus EBR alone may have resulted in a small reduction in overall and prostate-cancer mortality and metastases in higher risk disease but may increase sexual harms. EBR plus initiating neoadjuvant AD versus EBR plus initiating concurrent AD may result in little to no difference in mortality at 12 years and genitourinary toxicity at 3 years. Conventionally fractionated EBR versus ultra-hypofractionated EBR may result in little to no difference in mortality and metastasis at 5 years and urinary and bowel toxicity at 2 years. Limited evidence suggested that AS results in fewer harms than photodynamic therapy and laparoscopic RP resulted in more harms than robotic-assisted RP. There was little to no information on long-term comparative effectiveness of other treatments. No studies evaluated WW or AS in screen detected CLPC or MRI for risk assessment or were conducted since effective pharmacologic therapies for advanced disease. No studies assessed provider or hospital factors of RP comparative effectiveness. Conclusions. RP reduces mortality versus WW in clinically detected CLPC but causes more harms. Effectiveness may be limited to younger men, those with intermediate risk disease and requires many years to occur. AM results in little to no mortality difference versus RP or EBR plus AD. EBR plus AD reduces mortality versus EBR alone in higher risk CLPC but may worsen sexual function. Adding low-dose-rate BT to 3D-Conformal EBR and AD may reduce mortality in higher risk CLPC. Little information exists on other treatments or the effects of patient, tumor and provider factors. Large, long-term RCTs in PSA-detected and MRI staged CLPC are needed.