Comparative effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis.

Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.

Out-of-Hospital Research in the Era of Electronic Health Records.

Conducting out-of-hospital research is unique and challenging and requires tracking patients across multiple phases of care, using multiple sources of patient records and multiple hospitals. The logistics and strategies used for out-of-hospital research are distinct from other forms of clinical research. The increasing use of electronic health records (EHRs) by hospitals and emergency medical services (EMS) agencies presents a large opportunity for accelerating out-of-hospital research, as well as particular challenges. In this study, we describe seven key aspects of designing and implementing out-of-hospital research in the era of EHRs: (1) selection of research sites, (2) defining the patient population, (3) patient sampling and sample size calculations, (4) EMS data, (5) hospital selection, (6) handling missing data, and (7) statistical analysis. We use examples from a recent prospective out-of-hospital cohort study to illustrate these topics, including lessons learned.

Systemic Pharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline.

BACKGROUND: A 2007 American College of Physicians guideline addressed pharmacologic options for low back pain. New evidence and medications have now become available. PURPOSE: To review the current evidence on systemic pharmacologic therapies for acute or chronic nonradicular or radicular low back pain. DATA SOURCES: Ovid MEDLINE (January 2008 through November 2016), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. STUDY SELECTION: Randomized trials that reported pain, function, or harms of systemic medications versus placebo or another intervention. DATA EXTRACTION: One investigator abstracted data, and a second verified accuracy; 2 investigators independently assessed study quality. DATA SYNTHESIS: The number of trials ranged from 9 (benzodiazepines) to 70 (nonsteroidal anti-inflammatory drugs). New evidence found that acetaminophen was ineffective for acute low back pain, nonsteroidal anti-inflammatory drugs had smaller benefits for chronic low back pain than previously observed, duloxetine was effective for chronic low back pain, and benzodiazepines were ineffective for radiculopathy. For opioids, evidence remains limited to short-term trials showing modest effects for chronic low back pain; trials were not designed to assess serious harms. Skeletal muscle relaxants are effective for short-term pain relief in acute low back pain but caused sedation. Systemic corticosteroids do not seem to be effective. For effective interventions, pain relief was small to moderate and generally short-term; improvements in function were generally smaller. Evidence is insufficient to determine the effects of antiseizure medications. LIMITATIONS: Qualitatively synthesized new trials with prior meta-analyses. Only English-language studies were included, many of which had methodological shortcomings. Medications injected for local effects were not addressed. CONCLUSION: Several systemic medications for low back pain are associated with small to moderate, primarily short-term effects on pain. New evidence suggests that acetaminophen is ineffective for acute low back pain, and duloxetine is associated with modest effects for chronic low back pain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014014735).

Nonpharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline.

BACKGROUND: A 2007 American College of Physicians guideline addressed nonpharmacologic treatment options for low back pain. New evidence is now available. PURPOSE: To systematically review the current evidence on nonpharmacologic therapies for acute or chronic nonradicular or radicular low back pain. DATA SOURCES: Ovid MEDLINE (January 2008 through February 2016), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. STUDY SELECTION: Randomized trials of 9 nonpharmacologic options versus sham treatment, wait list, or usual care, or of 1 nonpharmacologic option versus another. DATA EXTRACTION: One investigator abstracted data, and a second checked abstractions for accuracy; 2 investigators independently assessed study quality. DATA SYNTHESIS: The number of trials evaluating nonpharmacologic therapies ranged from 2 (tai chi) to 121 (exercise). New evidence indicates that tai chi (strength of evidence [SOE], low) and mindfulness-based stress reduction (SOE, moderate) are effective for chronic low back pain and strengthens previous findings regarding the effectiveness of yoga (SOE, moderate). Evidence continues to support the effectiveness of exercise, psychological therapies, multidisciplinary rehabilitation, spinal manipulation, massage, and acupuncture for chronic low back pain (SOE, low to moderate). Limited evidence shows that acupuncture is modestly effective for acute low back pain (SOE, low). The magnitude of pain benefits was small to moderate and generally short term; effects on function generally were smaller than effects on pain. LIMITATION: Qualitatively synthesized new trials with prior meta-analyses, restricted to English-language studies; heterogeneity in treatment techniques; and inability to exclude placebo effects. CONCLUSION: Several nonpharmacologic therapies for primarily chronic low back pain are associated with small to moderate, usually short-term effects on pain; findings include new evidence on mind-body interventions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42014014735).

Benefits and Harms of Intensive Blood Pressure Treatment in Adults Aged 60 Years or Older: A Systematic Review and Meta-analysis.

BACKGROUND: Recent guidelines recommend a systolic blood pressure (SBP) goal of less than 150 mm Hg for adults aged 60 years or older, but the balance of benefits and harms is unclear in light of newer evidence. PURPOSE: To systematically review the effects of more versus less intensive BP control in older adults. DATA SOURCES: Multiple databases through January 2015 and MEDLINE to September 2016. STUDY SELECTION: 21 randomized, controlled trials comparing BP targets or treatment intensity, and 3 observational studies that assessed harms. DATA EXTRACTION: Two investigators extracted data, assessed study quality, and graded the evidence using published criteria. DATA SYNTHESIS: Nine trials provided high-strength evidence that BP control to less than 150/90 mm Hg reduces mortality (relative risk [RR], 0.90 [95% CI, 0.83 to 0.98]), cardiac events (RR, 0.77 [CI, 0.68 to 0.89]), and stroke (RR, 0.74 [CI, 0.65 to 0.84]). Six trials yielded low- to moderate-strength evidence that lower targets (≤140/85 mm Hg) are associated with marginally significant decreases in cardiac events (RR, 0.82 [CI, 0.64 to 1.00]) and stroke (RR, 0.79 [CI, 0.59 to 0.99]) and nonsignificantly fewer deaths (RR, 0.86 [CI, 0.69 to 1.06]). Low- to moderate-strength evidence showed that lower BP targets do not increase falls or cognitive impairment. LIMITATION: Data relevant to frail elderly adults and the effect of multimorbidity are limited. CONCLUSION: Treatment to at least current guideline standards for BP (<150/90 mm Hg) substantially improves health outcomes in older adults. There is less consistent evidence, largely from 1 trial targeting SBP less than 120 mm Hg, that lower BP targets are beneficial for high-risk patients. Lower BP targets did not increase falls or cognitive decline but are associated with hypotension, syncope, and greater medication burden. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO 2015: CRD42015017677).

Prenatal Depression Screening by Certified Nurse-Midwives, Oregon.

INTRODUCTION: About 18% of pregnant women have major or minor depression during pregnancy, but many are neither screened nor treated. Lack of treatment can have serious adverse consequences for the woman and her child. Since 2002, the American College of Nurse-Midwives has advised midwives to integrate prevention, universal screening, treatment, and/or referral for depression into the care they provide. The American College of Obstetricians and Gynecologists' 2015 guidelines recommend screening at least once in the perinatal period using a standardized, validated tool. A consensus has not been reached by professional organizations about the specifics of whether and when to screen for prenatal depression. The objective of this study is to understand the prenatal screening practices of midwives who practice in Oregon. METHODS: We surveyed all 162 Oregon-licensed certified nurse-midwives (CNMs). The survey asked about practice characteristics, demographics, screening, and perceived barriers to screening. The survey was administered electronically from October through December 2014. RESULTS: The response rate was 37%. Among the 53 CNM respondents who had provided prenatal care in the previous year, 50 (94%) reported screening for prenatal depression, and 38 (72%) reported the use of a standardized screening tool on more than 90% of prenatal patients. Thirty-five (66%) CNMs reported using the Edinburgh Postnatal Depression Scale. More than 60% of respondents indicated that availability of mental health services and insurance constraints were barriers to screening. DISCUSSION: We explored prenatal depression screening practices of CNMs. Most Oregon CNMs use a standardized screening tool. We suggest 2 strategies to overcome barriers to screening: incorporation of a standardized screening tool into electronic medical records and negotiation with insurance companies. More research is needed to clarify when and how often pregnant women should be screened for depression and how to increase the number of women who receive treatment.

Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation.

BACKGROUND: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. PURPOSE: To review studies of the effectiveness of breast cancer screening in average-risk women. DATA SOURCES: MEDLINE and Cochrane databases to 4 June 2015. STUDY SELECTION: English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes. DATA EXTRACTION: Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus. DATA SYNTHESIS: Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10,000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented per 10,000 women over 10 years); 0.67 for those aged 60 to 69 years (CI, 0.54 to 0.83) (5 trials; 21 deaths prevented per 10,000 women over 10 years); and 0.80 for those aged 70 to 74 years (CI, 0.51 to 1.28) (3 trials; 13 deaths prevented per 10,000 women over 10 years). Risk reduction was 25% to 31% for women aged 50 to 69 years in observational studies of mammography screening. All-cause mortality was not reduced with screening. Advanced breast cancer was reduced for women aged 50 years or older (RR, 0.62 [CI, 0.46 to 0.83]) (3 trials) but not those aged 39 to 49 years (RR, 0.98 [CI, 0.74 to 1.37]) (4 trials); less evidence supported this outcome. LIMITATIONS: Most trials used imaging technologies and treatments that are now outdated, and definitions of advanced breast cancer were heterogeneous. Studies of effectiveness based on risk factors, intervals, or other modalities were unavailable or methodologically limited. CONCLUSION: Breast cancer mortality is generally reduced with mammography screening, although estimates are not statistically significant at all ages and the magnitudes of effect are small. Advanced cancer is reduced with screening for women aged 50 years or older. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Interpreting the National Hospital Ambulatory Medical Care Survey: United States Emergency Department Opioid Prescribing, 2006-2010.

OBJECTIVES: Prescription opioid overdoses are a leading cause of death in the United States. Emergency departments (EDs) are potentially high-risk environments for doctor shopping and diversion. The hypothesis was that opioid prescribing rates from the ED have increased over time. METHODS: The authors analyzed data on ED discharges from the 2006 through 2010 NHAMCS, a probability sample of all U.S. EDs. The outcome was documentation of an opioid prescription on discharge. The primary independent predictor was time. Covariates included severity of pain, a pain-related discharge diagnosis, age, sex, race, payer, hospital ownership, and geographic location of hospital. Up to three discharge diagnoses were available in NHAMCS to identify "pain-related" (e.g., back pain, fracture, dental/jaw pain, nephrolithiasis) ED visits. Multivariate logistic regression was performed to assess the independent associations between opioid prescribing and predictors. All analyses incorporated NHAMCS survey weights, and all results are presented as national estimates. RESULTS: Opioids were prescribed for 18.7% (95% confidence interval = 17.7% to 19.7%) of all ED discharges, representing 18.8 million prescriptions per year. There were no significant temporal trends in opioid prescribing overall (adjusted p = 0.93). Pain-related discharge diagnoses that received the top three highest proportion of opioids prescriptions included nephrolithiasis (62.1%), neck pain (51.6%), and dental/jaw pain (49.7%). A pain-related discharge diagnosis, non-Hispanic white race, older age, male sex, uninsured status, and Western region were positively associated with opioid prescribing (p < 0.05). CONCLUSIONS: No temporal trend toward increased prescribing from 2006 to 2012 was found. These results suggest that problems with opioid overprescribing are multifactorial and not solely rooted in the ED.

Educational group visits for the management of chronic health conditions: a systematic review.

OBJECTIVE: Review the effectiveness of group visits (appointments of multiple patients) on quality of life, function, self-efficacy, utilization, and biophysical outcomes in randomized controlled trials of patients with chronic conditions. METHODS: We searched MEDLINE(®), Cochrane, CINAHL, and PsycINFO to January 2013 for English-language trials of educational group visits led by non-prescribing facilitators (e.g., peer educators). RESULTS: We report on 80 arthritis/falls (n=22), asthma/COPD (n=10), CHF/hypertension (n=12), diabetes (n=29), multiple conditions (n=4), and pain (n=4) studies. We found moderate evidence of improved short-term self-efficacy in patients with arthritis (10 studies) and diabetes (10 studies). We found no consistent evidence of improved quality of life; however a moderately strong body of evidence suggests peer-led community-based programs might improve quality of life and utilization in patients with multiple chronic conditions. Meta-analyses found short- (14 studies; mean change HbA1c=-0.27, CI=-0.44, 0.11) and long-term (10 studies; mean change HbA1c=-0.23, CI=-0.44, -0.02) glycemic improvement. CONCLUSIONS: Group visits may improve self-efficacy and glycemic control. There was little consistent evidence of improved quality of life, functional status, or utilization. PRACTICE IMPLICATIONS: Group visits represent a reasonable alternative for educating patients with chronic illness, though varied participation/retention suggests they should not be the sole alternative.

Continuous peripheral nerve block compared with single-injection peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Many practitioners consider continuous peripheral nerve blocks (cPNBs) to be superior to single-injection peripheral nerve blocks (siPNBs). Several randomized controlled trials have demonstrated improved pain control, patient satisfaction, and other outcomes for patients with cPNBs compared with patients with siPNBs, whereas other trials have not shown significant differences. We sought to clarify any potential advantages of cPNBs over siPNBs. METHODS: We conducted a systematic review and meta-analysis of all prospective, randomized trials comparing cPNBs with siPNBs. We used a validated systematic search strategy to identify potentially eligible studies. For studies meeting inclusion criteria, methodologic quality was scored independently by 2 reviewers. Data from the studies were abstracted and pooled for meta-analysis. RESULTS: Compared with siPNBs, cPNBs were associated with a decreased rating of worst pain on postoperative day 0 (effect size [ES], -1.29; 95% confidence interval [CI], -2.19 to -0.40; P = 0.005), postoperative day 1 (ES, -1.87; 95% CI, -2.44 to -1.31; P < 0.001), and postoperative day 2 (ES, -2.03; 95% CI, -2.78 to -1.290; P < 0.001); decreased overall opioid use (ES, -15.70; 95% CI, -21.84 to -9.55; P < 0.001); less nausea (ES, 0.633; 95% CI, 0.407-0.983; P = 0.043); and higher patient satisfaction scores (weighted mean difference, -2.04; 95% CI, 1.24-2.85; P < 0.001). CONCLUSIONS: Compared with siPNBs, cPNBs were associated with improved pain control, decreased need for opioid analgesics, less nausea, and greater patient satisfaction. The effect of cPNBs on other clinically relevant outcomes, such as complications, long-term functional outcomes, or costs, remains unclear.

Temporal daily associations between pain and sleep in adolescents with chronic pain versus healthy adolescents.

Adolescents with chronic pain frequently report sleep disturbances, particularly short sleep duration, night wakings, and poor sleep quality. Prior research has been limited by assessment of subjectively reported sleep only and lack of data on daily relationships between sleep and pain. The current study utilized multilevel modeling to compare daily associations between sleep and pain in adolescents with chronic pain and healthy adolescents. Ninety-seven adolescents (n=39 chronic pain; n=58 healthy) aged 12-18, 70.1% female participated. Adolescents completed pain diary ratings (0-10 NRS) and actigraphic sleep monitoring for 10 days. Actigraphic sleep variables (duration, efficiency, WASO) and self-reported sleep quality were tested as predictors of next-day pain, and daytime pain was tested as a predictor of sleep that night. Effects of age, gender, study group, and depressive symptoms on daily associations between sleep and pain were also tested. Multivariate analyses revealed that nighttime sleep (p<.001) and minutes awake after sleep onset (WASO) (p<.05) predicted next-day pain, with longer sleep duration and higher WASO associated with higher pain. Contrary to hypotheses, neither nighttime sleep quality nor sleep efficiency predicted pain the following day. The interaction between nighttime sleep efficiency and study group was significant, with adolescents with pain showing stronger associations between sleep efficiency and next-day pain than healthy participants (p=.05). Contrary to hypotheses, daytime pain did not predict nighttime sleep. Daily associations between pain and sleep suggest that further work is needed to identify specific adolescent sleep behaviors (e.g., compensatory sleep behaviors) that may be targeted in interventions.