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Hempel S.,Southern California Evidence based Practice Center | Newberry S.J.,Southern California Evidence based Practice Center | Maher A.R.,RAND | Maher A.R.,Cedars Sinai Medical Center | And 6 more authors.
JAMA - Journal of the American Medical Association | Year: 2012

Context: Probiotics are live microorganisms intended to confer a health benefit when consumed. One condition for which probiotics have been advocated is the diarrhea that is a common adverse effect of antibiotic use. Objective: To evaluate the evidence for probiotic use in the prevention and treatment of antibiotic-associated diarrhea (AAD). Data Sources: Twelve electronic databases were searched (DARE, Cochrane Library of Systematic Reviews, CENTRAL, PubMed, EMBASE, CINAHL, AMED, MANTIS, TOXLINE, ToxFILE, NTIS, and AGRICOLA) and references of included studies and reviews were screened from database inception to February 2012, without language restriction. Study Selection: Two independent reviewers identified parallel randomized controlled trials (RCTs) of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus) for the prevention or treatment of AAD. Data Extraction: Two independent reviewers extracted the data and assessed trial quality. Results: A total of 82 RCTs met inclusion criteria. The majority used Lactobacillusbased interventions alone or in combination with other genera; strains were poorly documented. The pooled relative risk in a DerSimonian-Laird random-effects metaanalysis of 63 RCTs, which included 11 811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk, 0.58; 95% CI, 0.50 to 0.68; P<.001; I 2, 54%; [risk difference, -0.07; 95% CI, -0.10 to -0.05], [number needed to treat, 13; 95% CI, 10.3 to 19.1]) in trials reporting on the number of patients with AAD. This result was relatively insensitive to numerous subgroup analyses. However, there exists significant heterogeneity in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation. Conclusions: The pooled evidence suggests that probiotics are associated with a reduction in AAD. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics. ©2012 American Medical Association. All rights reserved. Source


Coker T.R.,University of California at Los Angeles | Chan L.S.,University of Southern California | Newberry S.J.,Southern California Evidence based Practice Center | Limbos M.A.,University of Southern California | And 4 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: Acute otitis media (AOM) is the most common condition for which antibiotics are prescribed for US children; however, wide variation exists in diagnosis and treatment. Objectives: To perform a systematic review on AOM diagnosis, treatment, and the association of heptavalent pneumococcal conjugate vaccine (PCV7) use with AOM microbiology. Data Sources: PubMed, Cochrane Databases, and Web of Science, searched to identify articles published from January 1999 through July 2010. Study Selection: Diagnostic studies with a criterion standard, observational studies and randomized controlled trials comparing AOM microbiology with and without PCV7, and randomized controlled trials assessing antibiotic treatment. Data Extraction: Independent article review and study quality assessment by 2 investigators with consensus resolution of discrepancies. Results: Of 8945 citations screened, 135 were included. Meta-analysis was performed for comparisons with 3 or more trials. Few studies examined diagnosis; otoscopic findings of tympanicmembranebulging (positive likelihood ratio, 51 [95% confidence interval {CI}, 36-73]) and redness (positive likelihood ratio, 8.4 [95% CI, 7-11]) were associated with accurate diagnosis. In the few available studies, prevalence of Streptococcus pneumoniae decreased (eg, 33%-48% vs 23%-31% of AOM isolates), while that of Haemophilus influenzae increased (41%-43% vs 56%-57%) pre- vs post-PCV7. Short-term clinical success was higher for immediate use of ampicillin or amoxicillin vs placebo (73% vs 60%; pooled rate difference, 12% [95% CI, 5%-18%]; number needed to treat, 9 [95% CI, 6-20]), while increasing the rate of rash or diarrhea by 3% to 5%. Two of 4 studies showed greater clinical success for immediate vs delayed antibiotics (95% vs 80%; rate difference, 15% [95% CI, 6%-24%] and 86% vs 70%; rate difference, 16% [95% CI, 6%-26%]). Data are absent on long-term effects on antimicrobial resistance. Meta-analyses in general showed no significant differences in antibiotic comparative effectiveness. Conclusions: Otoscopic findings are critical to accurate AOM diagnosis. AOM microbiology has changed with use of PCV7. Antibiotics are modestly more effective than no treatment but cause adverse effects in 4% to 10% of children. Most antibiotics have comparable clinical success. ©2010 American Medical Association. All rights reserved. Source


Modarresi S.,West Los Angeles Medical Center | Motamedi D.,Cedars Sinai Medical Center | Jude C.M.,View Medical
American Journal of Roentgenology | Year: 2011

OBJECTIVE. The objectives of this article are to discuss the 10 distinct patterns of superior labral anteroposterior (SLAP) tears to facilitate adequate diagnosis and treatment. Correlations with clinical presentation, mechanism of injury, and treatment will enhance understanding. CONCLUSION. Imaging plays an important role in the diagnosis of SLAP tears. Knowledge of glenolabral anatomy, related structures and variants, proper imaging techniques, and a systematic approach to MRI interpretation is important in the diagnosis and treatment planning of the 10 types of SLAP lesions. Arthroscopy offers a means for definitive diagnosis. © American Roentgen Ray Society. Source


Garcia-Junco-Clemente P.,University of California at Los Angeles | Golshani P.,University of California at Los Angeles | Golshani P.,West Los Angeles Medical Center
Communicative and Integrative Biology | Year: 2014

PTEN (phosphatase and tensin homolog on chromosome ten) is a dual protein/lipid phosphatase that dephosphorylates PIP3, thereby inhibiting the AKT/mTOR pathway. This inhibition ultimately decreases protein translation, cell proliferation and cell growth. In the central nervous system, inhibition of PTEN leads to increased stem cell proliferation, somatic, dendritic and axonal growth, accelerated spine maturation, diminished synaptic plasticity, and altered intrinsic excitability. In agreement with these findings, patients carrying single-copy inactivating mutations of PTEN suffer from autism, macrocephaly, mental retardation, and epilepsy. Understanding the mechanisms through which PTEN modulates the structure, function, and plasticity of cortical networks is a major focus of study. Preventing and reversing the changes induced by loss of Pten in model animals will pave the way for treatments in humans. © 2014 Landes Bioscience. Source


Jankovic B.,Cedars Sinai Medical Center | Jankovic B.,West Los Angeles Veterans Administration Medical Center | Le K.T.,Cedars Sinai Medical Center | Le K.T.,West Los Angeles Veterans Administration Medical Center | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: The link between Hashimoto's thyroiditis (HT) and papillary thyroid cancer (PTC) has long been a topic of controversy. There are conflicting reports; some suggest that these two are positively correlated, whereas other studies report no relationship. Evidence Acquisition: We performed a systematic literature review of original studies that investigated the correlation between HT and PTC. The two main search engines used to identify articles were OVID Medline and PubMed. The included studies were categorized into a fine-needle aspiration biopsy (FNAB) group and an archival thyroidectomy specimen group. Evidence Synthesis: There is no clear evidence to support the correlation between HT and PTC. Population-based FNAB studies report no linkage, whereas many of the studies of thyroidectomy specimens report a positive relationship. The average prevalence rate of PTC in patients with HT was 1.20% in 8 FNA studies of 18 023 specimens and 27.56% in 8 archival thyroidectomy studies of 9 884 specimens. The relative risk ratio of finding evidence of PTC in HT specimens ranged from .39 to 1.00 in the FNA group (average RR = .69) in contrast to 1.15 to 4.16 from the archival thyroidectomy studies (average RR = 1.59). In addition, there are many studies in the literature that propose a genetic link between HT and PTC involving the PI3K/Akt pathway and RET/PTC gene rearrangements. Conclusion: Although limited by the lack of definitive pathology, population-based FNA studies did not find a statistically significant correlation between HT and PTC. Thyroidectomy studies, which reported a statistically significant positive correlation, are subject to selection bias. More prospective studies with longer follow-up are needed to further elucidate this relationship. Copyright © 2013 by The Endocrine Society. Source

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