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Original Research | 
Yoosoo Chang, MD, PhD; Seungho Ryu, MD, PhD; Yuni Choi, BS; Yiyi Zhang, PhD; Juhee Cho, PhD; Min-Jung Kwon, MD, PhD; Young Youl Hyun, MD, PhD; Kyu-Beck Lee, MD, PhD; Hyang Kim, MD, PhD; Hyun-Suk Jung, MD; Kyung Eun Yun, MD, PhD; Jiin Ahn, MSPH; Sanjay Rampal, MD, PhD; Di Zhao, PhD; Byung-Seong Suh, MD, PhD; Eun Cheol Chung, MD, PhD; Hocheol Shin, MD, PhD; Roberto Pastor-Barriuso, PhD; and Eliseo Guallar, MD, DrPH
Background:The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored. Objective:To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women. Design:Prospective cohort study. Setting:Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea. Participants:62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline. Measurements:Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Results:During 369 088 person-years of follow-up, 906 incident CKD cases were identified. The multivariable-adjusted differences in 5-year cumulative incidence of CKD in underweight, overweight, and obese participants compared with normal-weight participants were −4.0 (95% CI, −7.8 to −0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively. These associations were consistently seen in all clinically relevant subgroups. Limitation:Chronic kidney disease was identified by a single measurement at each visit. Conclusion:Overweight and obesity are associated with an increased incidence of CKD in metabolically healthy young and middle-aged participants. These findings show that metabolically healthy obesity is not a harmless condition and that the obese phenotype, regardless of metabolic abnormalities, can adversely affect renal function. Primary Funding Source:None.
Topics: obesity, kidney failure, chronic, overweight, body mass index procedure
Reviews | 
Gerald Gartlehner, MD, MPH; Bradley N. Gaynes, MD, MPH; Halle R. Amick, MSPH; Gary N. Asher, MD, MPH; Laura C. Morgan, MA; Emmanuel Coker-Schwimmer, MPH; Catherine Forneris, PhD, ABPP; Erin Boland, BA; Linda J. Lux, PhD; Susan Gaylord, PhD; Carla Bann, PhD; Christiane Barbara Pierl, PhD, MPH; and Kathleen N. Lohr, PhD, MPhil, MA
Includes: Supplemental Content
Background:Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear. Purpose:To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD. Data Sources:English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research. Study Selection:Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms. Data Extraction:Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings. Data Synthesis:45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief. Limitation:High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence. Conclusion:Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD. Primary Funding Source:Agency for Healthcare Research and Quality.
Topics: antidepressive agents, exercise, antidepressive agents, second-generation, major depressive disorder, american college of physicians, disease remission
Reviews | 
Valerie Forman-Hoffman, PhD, MPH; Emily McClure, MSPH; Joni McKeeman, PhD; Charles T. Wood, MD; Jennifer Cook Middleton, PhD; Asheley C. Skinner, PhD; Eliana M. Perrin, MD, MPH; and Meera Viswanathan, PhD
Background:Major depressive disorder (MDD) is common among children and adolescents and is associated with functional impairment and suicide. Purpose:To update the 2009 U.S. Preventive Services Task Force (USPSTF) systematic review on screening for and treatment of MDD in children and adolescents in primary care settings. Data Sources:Several electronic searches (May 2007 to February 2015) and searches of reference lists of published literature. Study Selection:Trials and recent systematic reviews of treatment, test–retest studies of screening, and trials and large cohort studies for harms. Data Extraction:Data were abstracted by 1 investigator and checked by another; 2 investigators independently assessed study quality. Data Synthesis:Limited evidence from 5 studies showed that such tools as the Beck Depression Inventory and Patient Health Questionnaire for Adolescents had reasonable accuracy for identifying MDD among adolescents in primary care settings. Six trials evaluated treatment. Several individual fair- and good-quality studies of fluoxetine, combined fluoxetine and cognitive behavioral therapy, escitalopram, and collaborative care demonstrated benefits of treatment among adolescents, with no associated harms. Limitation:The review included only English-language studies, narrow inclusion criteria focused only on MDD, high thresholds for quality, potential publication bias, limited data on harms, and sparse evidence on long-term outcomes of screening and treatment among children younger than 12 years. Conclusion:No evidence was found of a direct link between screening children and adolescents for MDD in primary care or similar settings and depression or other health-related outcomes. Evidence showed that some screening tools are accurate and some treatments are beneficial among adolescents (but not younger children), with no evidence of associated harms. Primary Funding Source:Agency for Healthcare Research and Quality.
Topics: major depressive disorder, depressive disorders
Clinical Guidelines | 
Amir Qaseem, MD, PhD, MHA; Michael J. Barry, MD; Devan Kansagara, MD, MCR, for the Clinical Guidelines Committee of the American College of Physicians
Description:The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness of treatment with second-generation antidepressants versus nonpharmacologic treatments for major depressive disorder in adults. Methods:This guideline is based on a systematic review of published, English-language, randomized, controlled trials from 1990 through September 2015 identified using several databases and through hand searches of references of relevant studies. Interventions evaluated include psychotherapies, complementary and alternative medicines (including acupuncture, ω-3 fatty acids, S-adenosyl-l-methionine, St. John's wort [Hypericum perforatum]), exercise, and second-generation antidepressants. Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with major depressive disorder. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system. Recommendation:ACP recommends that clinicians select between either cognitive behavioral therapy or second-generation antidepressants to treat patients with major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient (Grade: strong recommendation, moderate-quality evidence).
Topics: combined modality therapy, infant, small for gestational age, major depressive disorder
Clinical Guidelines | 
Albert L. Siu, MD, MSPH, on behalf of the U.S. Preventive Services Task Force
Description:Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for major depressive disorder (MDD) in children and adolescents. Methods:The USPSTF reviewed the evidence on the benefits and harms of screening; the accuracy of primary care–feasible screening tests; and the benefits and harms of treatment with psychotherapy, medications, and collaborative care models in patients aged 7 to 18 years. Population:This recommendation applies to children and adolescents aged 18 years or younger who do not have a diagnosis of MDD. Recommendation:The USPSTF recommends screening for MDD in adolescents aged 12 to 18 years. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. (B recommendation)The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for MDD in children aged 11 years or younger. (I statement)
Topics: psychotherapy, selective serotonin re-uptake inhibitors, major depressive disorder, screening test, depression screening, collaborative care, depressive disorders
Editorials | 
John W. Williams Jr., MD, MHSc; and Gary Maslow, MD, MPH
This issue includes guidelines from the U.S. Preventive Services Task Force on screening for depression in children and adolescents and the American College of Physicians on treating adults with depression. The editorialists discuss the recommendations and why they believe that current times offer opportunities to improve the care of persons with depression.
Topics: depressive disorders, depression guidelines, depression screening, therapeutics
Topics: depression screening
Topics: major depressive disorder
Original Research | 
Raine Sihvonen, MD, PhD; Martin Englund, MD, PhD; Aleksandra Turkiewicz, MSc; Teppo L.N. Järvinen, MD, PhD, for the Finnish Degenerative Meniscal Lesion Study Group
Background:Recent evidence shows that arthroscopic partial meniscectomy (APM) offers no benefit over conservative treatment of patients with a degenerative meniscus tear. However, patients who report mechanical symptoms (sensations of knee catching or locking) may benefit from APM. Objective:To assess whether APM improves mechanical symptoms better than sham surgery. Design:Randomized, patient- and outcome assessor–blinded, sham surgery–controlled, multicenter trial. (ClinicalTrials.gov: NCT00549172) Setting:5 orthopedic clinics in Finland. Patients:Adults (aged 35 to 65 years) with a degenerative medial meniscus tear and no knee osteoarthritis. Intervention:APM or sham surgery. Measurements:Patients' self-report of mechanical symptoms before surgery and at 2, 6, and 12 months after surgery. Results:70 patients were randomly assigned to APM, and 76 were assigned to sham surgery. Thirty-two patients (46%) in the APM group and 37 (49%) in the sham surgery group reported catching or locking before surgery; the corresponding numbers at any follow-up were 34 (49%) and 33 (43%), with a risk difference of 0.03 (95% CI, −0.06 to 0.12). In the subgroup of 69 patients with preoperative catching or locking, the risk difference was 0.07 (CI, −0.08 to 0.22). Limitation:Analyses were post hoc, and the results are only generalizable to knee catching and occasional locking because few patients reported other types of mechanical symptoms. Conclusion:Resection of a torn meniscus has no added benefit over sham surgery to relieve knee catching or occasional locking. These findings question whether mechanical symptoms are caused by a degenerative meniscus tear and prompt caution in using patients' self-report of these symptoms as an indication for APM. Primary Funding Source:Academy of Finland.
Topics: arthroscopy, knee meniscus tears, partial meniscectomy of knee, knee region, follow-up, knee joint
Editorials | 
Jeffrey N. Katz, MD, MSc; and Morgan H. Jones, MD, MPH
In this issue, Sihvonen and colleagues provide evidence from a rigorous, randomized, controlled trial that arthroscopic partial meniscectomy (APM) is no more beneficial than arthroscopic lavage without meniscal resection in reducing catching and locking in patients with degenerative meniscal tear. Prior findings from this trial showed that APM did not improve pain or function. The editorialists discuss how these findings illustrate that diagnostic and therapeutic paradigms derived from the management of younger persons without coexisting problems may not translate to older persons with more complex pathoanatomy.
Topics: knee meniscus tears
Topics: arthroscopy, knee meniscus tears, partial meniscectomy of knee
Ideas and Opinions | 
Kathleen M. Mazor, EdD; Kelly M. Smith, PhD; Kimberly A. Fisher, MD; and Thomas H. Gallagher, MD
Although most healthcare systems encourage patients to provide feedback about the care they received, few choose to do so. This article proposes several strategies for encouraging patients to speak up about their concerns and why it may be beneficial for healthcare systems to respond to these issues in a timely manner.
Topics: patient-centered care
Ideas and Opinions | 
Timothy P. Hofer, MD, MSc; Jeremy B. Sussman, MD, MSc; and Rodney A. Hayward, MD
The 2013 lipid guidelines from the American College of Cardiology and the American Heart Association recommend that statin therapy be guided by cardiovascular risk rather than by a specific low-density lipoprotein (LDL) cholesterol level or target. It has been argued, however, that recent evidence that nonstatin lipid-lowering agents reduce cardiovascular events supports a return to therapy guided by an LDL cholesterol level or target. The authors argue that these recent findings actually support a move away from such an approach and the adoption of benefit-based, tailored treatment.
Topics: ldl cholesterol lipoproteins, american heart association, guidelines, lipids, american college of cardiology, ezetimibe
Original Research | 
Tobias Freund, MD; Frank Peters-Klimm, MD; Cynthia M. Boyd, MD; Cornelia Mahler, MA; Jochen Gensichen, MD; Antje Erler, MD; Martin Beyer, MA; Matthias Gondan, PhD; Justine Rochon, MSc; Ferdinand M. Gerlach, MD; and Joachim Szecsenyi, MD
Includes: Supplemental Content
Background:Patients with multiple chronic conditions are at high risk for potentially avoidable hospitalizations, which may be reduced by care coordination and self-management support. Medical assistants are an increasingly available resource for patient care in primary care practices. Objective:To determine whether protocol-based care management delivered by medical assistants improves care in patients at high risk for future hospitalization in primary care. Design:Two-year cluster randomized clinical trial. (Current Controlled Trials: ISRCTN56104508) Setting:115 primary care practices in Germany. Patients:2076 patients with type 2 diabetes, chronic obstructive pulmonary disease, or chronic heart failure and a likelihood of hospitalization in the upper quartile of the population, as predicted by an analysis of insurance data. Intervention:Protocol-based care management, including structured assessment, action planning, and monitoring delivered by medical assistants, compared with usual care. Measurements:All-cause hospitalizations at 12 months (primary outcome) and quality-of-life scores (12-Item Short Form Health Survey [SF-12] and EuroQol instrument [EQ-5D]). Results:Included patients had an average of 4 co-occurring chronic conditions. All-cause hospitalizations did not differ between groups at 12 months (risk ratio [RR], 1.01 [95% CI, 0.87 to 1.18]) and 24 months (RR, 0.98 [CI, 0.85 to 1.12]). Quality of life (differences, 1.16 [CI, 0.24 to 2.08] on SF-12 physical component and 1.68 [CI, 0.60 to 2.77] on SF-12 mental component) and general health (difference on EQ-5D, 0.03 [CI, 0.00 to 0.05]) improved significantly at 24 months. Intervention costs totaled $10 per patient per month. Limitation:Small number of primary care practices and low intensity of intervention. Conclusion:This low-intensity intervention did not reduce all-cause hospitalizations but showed positive effects on quality of life at reasonable costs in high-risk multimorbid patients. Primary Funding Source:AOK Baden-Württemberg and AOK Bundesverband.
Topics: hospitalization, patient care management, primary health care, chronic disease, quality of life, chronic obstructive airway disease, self-management, follow-up, primary care physicians, diabetes mellitus, type 2, heart failure, chronic
Original Research | 
Lindsey R. Baden, MD; Etienne Karita, MD; Gaudensia Mutua, MBChB; Linda-Gail Bekker, MD; Glenda Gray, MBBCh; Liesl Page-Shipp, MD; Stephen R. Walsh, MD; Julien Nyombayire, MD; Omu Anzala, MBChB, PhD; Surita Roux, MD; Fatima Laher, MBBCh; Craig Innes, MD; Michael S. Seaman, PhD; Yehuda Z. Cohen, MD; Lauren Peter; Nicole Frahm, PhD; M. Juliana McElrath, MD, PhD; Peter Hayes, PhD; Edith Swann, PhD; Nicole Grunenberg, MD; Maria Grazia-Pau, MSc; Mo Weijtens, PhD; Jerry Sadoff, MD; Len Dally, MSc; Angela Lombardo, PhD; Jill Gilmour, PhD; Josephine Cox, PhD; Raphael Dolin, MD; Patricia Fast, MD, PhD; Dan H. Barouch, MD, PhD; Dagna S. Laufer, MD, for the B003-IPCAVD004-HVTN091 Study Group
Includes: Supplemental Content
Background:A prophylactic HIV-1 vaccine is a global health priority. Objective:To assess a novel vaccine platform as a prophylactic HIV-1 regimen. Design:Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149) Setting:United States, East Africa, and South Africa. Patients:Healthy adults without HIV infection. Intervention:2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations. Measurements:Safety and immunogenicity and the effect of baseline vector immunity. Results:217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30–300 to 3000). The heterologous regimen of Ad26–Ad35 elicited significantly higher EnvA antibody titers than Ad35–Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States. Limitations:Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown. Conclusion:Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response. Primary Funding Source:International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.
Topics: hiv-1, vaccines, safety, adenovirus infections, enzyme-linked immunosorbent assay, adenoviruses, vaccination
In this issue, Freund and colleagues report a trial of a modest intervention powered by medical assistants to keep patients out of the hospital. The editorialist notes that we do well with the care of acute conditions and rescue care, which the health care system devotes considerable resources to. To similarly master chronic illness care will require similar resources and careful coordination of appropriately trained personnel.
Topics: hospitalization, primary health care
Reviews | 
John Eng, MD; Renee F. Wilson, MS; Rathan M. Subramaniam, MD, PhD, MPH; Allen Zhang, BS; Catalina Suarez-Cuervo, MD; Sharon Turban, MD, MHS; Michael J. Choi, MD; Cheryl Sherrod, MD, MPH; Susan Hutfless, PhD; Emmanuel E. Iyoha, MBChB, MPH; and Eric B. Bass, MD, MPH
Background:Iodinated contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN). Purpose:To compare CIN risk for contrast media within and between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures. Data Sources:PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015. Study Selection:Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging. Data Extraction:Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results. Data Synthesis:None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 [95% CI, 0.65 to 0.99]; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk. Limitations:Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment. Conclusion:No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance. Primary Funding Source:Agency for Healthcare Research and Quality.
Topics: radiographic contrast agent nephropathy, contrast media
Reviews | 
Rathan M. Subramaniam, MD, PhD, MPH; Catalina Suarez-Cuervo, MD; Renee F. Wilson, MS; Sharon Turban, MD, MHS; Allen Zhang, BS; Cheryl Sherrod, MD, MPH; Jonathan Aboagye, MD, MPH; John Eng, MD; Michael J. Choi, MD; Susan Hutfless, PhD; and Eric B. Bass, MD, MPH
Background:N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN). Purpose:To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media. Data Sources:MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias of studies and overall strength of evidence (SOE) were assessed. Study Selection:Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis. Data Extraction:Two reviewers independently extracted data and assessed study quality. Data Synthesis:Low-dose N-acetylcysteine compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine versus N-acetylcysteine (RR, 0.52 [CI, 0.29 to 0.93]; low SOE) had clinically important and statistically significant benefits. The following 3 comparisons suggested a clinically important difference that was not statistically significant: sodium bicarbonate versus IV saline in patients receiving low-osmolar contrast media (RR, 0.65 [CI, 0.33 to 1.25]; low SOE), statins plus IV saline versus IV saline (RR, 0.68 [CI, 0.39 to 1.20]; low SOE), and ascorbic acid versus IV saline (RR, 0.72 [CI, 0.48 to 1.01]; low SOE). Strength of evidence was generally insufficient for comparisons of the need for renal replacement, cardiac events, and mortality. Limitation:Too few studies were done in patients receiving IV contrast media. Conclusion:The greatest reduction in CIN was seen with N-acetylcysteine in patients receiving LOCM and with statins plus N-acetylcysteine. Primary Funding Source:Agency for Healthcare Research and Quality.
Topics: statins, radiographic contrast agent nephropathy, contrast media, acetylcysteine, sodium bicarbonate, ascorbic acid, normal saline, saline solution
Ideas and Opinions | 
Hannah L. Semigran, BA; Ateev Mehrotra, MD, MPH, MS; and Ann Hwang, MD, MPhil
The current medical billing system is a common source of patients' frustration with health care. Most patients are inundated with bills and insurance statements that are sometimes confusing or inaccurate and often arrive long after their health care encounters. This article proposes strategies for providing real-time point-of-care information on health care costs to patients.
Topics: drowning, patient-centered care, Billing and payment, social cognition and emotional assessment
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