1.Gemifloxacin for the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis: a meta-analysis of randomized controlled trials.
Lei ZHANG ; Rui WANG ; Matthew E FALAGAS ; Falagas E MATTHEW ; Liang-an CHEN ; You-ning LIU
Chinese Medical Journal 2012;125(4):687-695
BACKGROUNDGemifloxacin is a fluoroquinolone antibiotic with broad spectrum of antibacterial activity. The aim of the study was to evaluate the comparative effectiveness and safety of gemifloxacin for the treatment of patients with community-acquired pneumonia (CAP) or acute exacerbation of chronic bronchitis (AECB).
METHODSWe performed a meta-analysis of randomized controlled trials (RCTs) comparing gemifloxacin with other approved antibiotics. The PubMed, EMBASE, Chinese Biomedical Literature Database and the Cochrane Central Register of Controlled Trials were searched, with no language restrictions.
RESULTSTen RCTs, comparing gemifloxacin with other quinolones (in 5 RCTs) and β-lactams and/or macrolides (in 5 RCTs), involving 3940 patients, were included in this meta-analysis. Overall, the treatment success was higher for gemifloxacin when compared with other antibiotics (odds ratio 1.39, 95% confidence interval 1.15 - 1.68 in intention-to-treat patients, and 1.33, 1.02 - 1.73 in clinically evaluable patients). There was no significant difference between the compared antibiotics regarding microbiological success (1.19, 0.84 - 1.68) or all-cause mortality (0.82, 0.41 - 1.63). The total drug related adverse events were similar for gemifloxacin when compared with other quinolones (0.89, 0.56 - 1.41), while lower when compared with β-lactams and/or macrolides (0.71, 0.57 - 0.89). In subgroup analyses, administration of gemifloxacin was associated with fewer cases of diarrhoea and more rashes compared with other antibiotics (0.66, 0.48 - 0.91, and 2.36, 1.18 - 4.74, respectively).
CONCLUSIONSThe available evidence suggests that gemifloxacin 320 mg oral daily is equivalent or superior to other approved antibiotics in effectiveness and safety for CAP and AECB. The development of rash represents potential limitation of gemifloxacin.
Anti-Bacterial Agents ; therapeutic use ; Bronchitis, Chronic ; drug therapy ; Community-Acquired Infections ; drug therapy ; Fluoroquinolones ; therapeutic use ; Humans ; Naphthyridines ; therapeutic use ; Pneumonia ; drug therapy ; Quinolones ; therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome
2.Gastroesophageal Reflux Disease Is Not Associated With Jackhammer Esophagus: A Case-control Study
Matthew WOO ; Andy LIU ; Lynn WILSACK ; Dorothy LI ; Milli GUPTA ; Yasmin NASSER ; Michelle BURESI ; Michael CURLEY ; Christopher N ANDREWS
Journal of Neurogastroenterology and Motility 2020;26(2):224-231
Background/Aims:
The pathophysiology of jackhammer esophagus (JE) remains unknown but may be related to gastroesophageal reflux disease or medication use. We aim to determine if pathologic acid exposure or the use of specific classes of medications (based on the mechanism of action) is associated with JE.
Methods:
High-resolution manometry (HRM) studies from November 2013 to March 2019 with a diagnosis of JE were identified and compared to symptomatic control patients with normal HRM. Esophageal acid exposure and medication use were compared between groups. Multivariate regression analysis was performed to look for predictors of mean distal contractile integral.
Results:
Forty-two JE and 127 control patients were included in the study. Twenty-two (52%) JE and 82 (65%) control patients underwent both HRM and ambulatory pH monitoring. Two (9%) JE patients and 14 (17%) of controls had evidence of abnormal acid exposure (DeMeester score > 14.7); this difference was not significant (P = 0.290). Thirty-six (86%) JE and 127 (100%) control patients had complete medication lists. Significantly more JE patients were on long-acting beta agonists (LABA) (JE = 5, control = 4; P = 0.026) and calcium channel blockers (CCB) (JE = 5, control = 3; P = 0.014). Regular opioids (β = 0.298, P = 0.042), CCB (β = 0.308, P = 0.035), and inhaled anticholinergics (β = 0.361, P = 0.049) predicted mean distal contractile integral (R2 = 0.082, F = 4.8; P = 0.003).
Conclusions
Pathologic acid exposure does not appear to be associated with JE. JE patients had increased CCB and LABA use. The unexpected finding of increased LABA use warrants more investigation and may provide support for a cholinergic etiology of JE.
3.Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma.
David COGDELL ; Woonbok CHUNG ; Yuexin LIU ; J Matthew MCDONALD ; Kenneth ALDAPE ; Jean-Pierre J ISSA ; Gregory N FULLER ; Wei ZHANG
Chinese Journal of Cancer 2011;30(4):247-253
Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.
Astrocytoma
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genetics
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metabolism
;
pathology
;
Cell Adhesion Molecules
;
genetics
;
metabolism
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Cell Line, Tumor
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Central Nervous System Neoplasms
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genetics
;
metabolism
;
pathology
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CpG Islands
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genetics
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DNA Methylation
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Down-Regulation
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Gene Deletion
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Glioblastoma
;
genetics
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metabolism
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pathology
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Humans
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Oligodendroglioma
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genetics
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metabolism
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pathology
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Promoter Regions, Genetic
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genetics
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Survival Rate
4.Identification of conserved regulatory elements in mammalian promoter regions: a case study using the PCK1 promoter.
George E LIU ; Matthew T WEIRAUCH ; Curtis P Van TASSELL ; Robert W LI ; Tad S SONSTEGARD ; Lakshmi K MATUKUMALLI ; Erin E CONNOR ; Richard W HANSON ; Jianqi YANG
Genomics, Proteomics & Bioinformatics 2008;6(3-4):129-143
A systematic phylogenetic footprinting approach was performed to identify conserved transcription factor binding sites (TFBSs) in mammalian promoter regions using human, mouse and rat sequence alignments. We found that the score distributions of most binding site models did not follow the Gaussian distribution required by many statistical methods. Therefore, we performed an empirical test to establish the optimal threshold for each model. We gauged our computational predictions by comparing with previously known TFBSs in the PCK1 gene promoter of the cytosolic isoform of phosphoenolpyruvate carboxykinase, and achieved a sensitivity of 75% and a specificity of approximately 32%. Almost all known sites overlapped with predicted sites, and several new putative TFBSs were also identified. We validated a predicted SP1 binding site in the control of PCK1 transcription using gel shift and reporter assays. Finally, we applied our computational approach to the prediction of putative TFBSs within the promoter regions of all available RefSeq genes. Our full set of TFBS predictions is freely available at http://bfgl.anri.barc.usda.gov/tfbsConsSites.
Algorithms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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genetics
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Cell Line, Tumor
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Computational Biology
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methods
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Conserved Sequence
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Electrophoretic Mobility Shift Assay
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Humans
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Intracellular Signaling Peptides and Proteins
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genetics
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Luciferases
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genetics
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metabolism
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Mice
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Normal Distribution
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Oligonucleotides
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genetics
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metabolism
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Phosphoenolpyruvate Carboxykinase (GTP)
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genetics
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Promoter Regions, Genetic
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genetics
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Protein Binding
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Rats
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Recombinant Fusion Proteins
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genetics
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metabolism
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Regulatory Sequences, Nucleic Acid
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genetics
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Reproducibility of Results
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Sp1 Transcription Factor
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genetics
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metabolism
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Transcription Factors
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metabolism
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Transfection
5.Frequent hospital admissions in Singapore: clinical risk factors and impact of socioeconomic status.
Lian Leng LOW ; Wei Yi TAY ; Matthew Joo Ming NG ; Shu Yun TAN ; Nan LIU ; Kheng Hock LEE
Singapore medical journal 2018;59(1):39-43
INTRODUCTIONFrequent admitters to hospitals are high-cost patients who strain finite healthcare resources. However, the exact risk factors for frequent admissions, which can be used to guide risk stratification and design effective interventions locally, remain unknown. Our study aimed to identify the clinical and sociodemographic risk factors associated with frequent hospital admissions in Singapore.
METHODSAn observational study was conducted using retrospective 2014 data from the administrative database at Singapore General Hospital, Singapore. Variables were identified a priori and included patient demographics, comorbidities, prior healthcare utilisation, and clinical and laboratory variables during the index admission. Multivariate logistic regression analysis was used to identify independent risk factors for frequent admissions.
RESULTSA total of 16,306 unique patients were analysed and 1,640 (10.1%) patients were classified as frequent admitters. On multivariate logistic regression, 16 variables were independently associated with frequent hospital admissions, including age, cerebrovascular disease, history of malignancy, haemoglobin, serum creatinine, serum albumin, and number of specialist outpatient clinic visits, emergency department visits, admissions preceding index admission and medications dispensed at discharge. Patients staying in public rental housing had a 30% higher risk of being a frequent admitter after adjusting for demographics and clinical conditions.
CONCLUSIONOur study, the first in our knowledge to examine the clinical risk factors for frequent admissions in Singapore, validated the use of public rental housing as a sensitive indicator of area-level socioeconomic status in Singapore. These risk factors can be used to identify high-risk patients in the hospital so that they can receive interventions that reduce readmission risk.
6.Impact of medical school responses during the COVID-19 pandemic on student satisfaction: a nationwide survey of US medical students
Isaac E. KIM JR. ; Daniel D. KIM ; Juliana E. KIM ; Elliott REBELLO ; David CHUNG ; Parker WOOLLEY ; Daniel LEE ; Brittany A. BORDEN ; Aaron WANG ; Douglas VILLALTA ; Agatha SUTHERLAND ; Sebastian DE ARMAS ; Matthew LIU ; Hannah KIM ; Grace Sora AHN ; Reed GEISLER ; Alexander YANG ; Bowon JOUNG ; John SLATE-ROMANO ; Michal RAJSKI ; Alison E. KIM ; Roxanne VREES ; Kristina MONTEIRO
Korean Journal of Medical Education 2022;34(2):167-174
Purpose:
Medical schools have faced various challenges in preparing their clinical students for the frontlines of a pandemic. This study investigated medical students’ satisfaction with their institutions during the coronavirus disease 2019 (COVID-19) pandemic with the intention of guiding educators in future public health crises.
Methods:
In this cross-sectional study surveying students in clinical rotations, the primary outcome was overall satisfaction regarding medical schools’ responses to the pandemic, and the four secondary outcomes were school communication, exposure to COVID-19, availability of personal protective equipment, and access to COVID-19 testing.
Results:
The survey was distributed to ten medical schools, of which 430 students responded for a response rate of 13.0%. While most students were satisfied (61.9%, n=266) with their schools’ response, more than one in five (21.9%, n=94) were dissatisfied. Among the four secondary outcomes, communication with students was most predictive of overall satisfaction.
Conclusion
In future crises, schools can best improve student satisfaction by prioritizing timely communication.
7.Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE)
Martin J. O’DONNELL ; Matthew MCQUEEN ; Allan SNIDERMAN ; Guillaume PARE ; Xingyu WANG ; Graeme J. HANKEY ; Sumathy RANGARAJAN ; Siu Lim CHIN ; Purnima RAO-MELACINI ; John FERGUSON ; Denis XAVIER ; Liu LISHENG ; Hongye ZHANG ; Prem PAIS ; Patricio LOPEZ-JARAMILLO ; Albertino DAMASCENO ; Peter LANGHORNE ; Annika ROSENGREN ; Antonio L. DANS ; Ahmed ELSAYED ; Alvaro AVEZUM ; Charles MONDO ; Conor JUDGE ; Hans-Christoph DIENER ; Danuta RYGLEWICZ ; Anna CZLONKOWSKA ; Nana POGOSOVA ; Christian WEIMAR ; Romana IQBAL ; Rafael DIAZ ; Khalid YUSOFF ; Afzalhussein YUSUFALI ; Aytekin OGUZ ; Ernesto PENAHERRERA ; Fernando LANAS ; Okechukwu S. OGAH ; Adesola OGUNNIYI ; Helle K. IVERSEN ; German MALAGA ; Zvonko RUMBOLDT ; Shahram OVEISGHARAN ; Fawaz AL HUSSAIN ; Yongchai NILANONT ; Salim YUSUF ;
Journal of Stroke 2022;24(2):224-235
Background:
and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes.
Methods:
Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH).
Results:
Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001).
Conclusions
The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.
8.Resident involvement in the prostatic urethral lift: implementing innovative technology in an academic setting.
Ridwan ALAM ; Matthew J RABINOWITZ ; Taylor P KOHN ; Vanessa N PEÑA ; James L LIU ; Yasin BHANJI ; Amin S HERATI
Asian Journal of Andrology 2021;23(6):616-620
Adoption of the prostatic urethral lift (PUL) as a treatment for benign prostatic hyperplasia highlights the importance of training residents with novel technology without compromising patient care. This study examines the effect of resident involvement during PUL on patient and procedural outcomes. Retrospective chart review was conducted on all consecutive PUL cases performed by a single academic urologist between October 2017 and November 2019. Trainees in post-graduate year (PGY) 1-3 are considered junior residents, while those in PGY 4-6 are senior residents. The International Prostate Symptom Score (IPSS) and quality of life (QOL) scores were used to measure outcomes. Simple and mixed-effects linear regression models were used to compare differences. There were 110 patients with a median age of 66.4 years. Residents were involved in 73 cases (66.4%), and senior residents were involved in 31 of those cases. Resident involvement was not associated with adverse perioperative outcomes with respect to the number of implants fired, the percentage of implants successfully placed, or the postoperative catheterization rate. After adjustment for confounding factors, junior residents were associated with significantly longer case length compared to the attending alone (+12.6 min, P = 0.003) but senior residents were not (+2.4 min, P = 0.59). IPSS and QOL scores were not significantly affected by resident involvement (P = 0.12 and P = 0.21, respectively). The presence of surgeons-in-training, particularly those in the early stages, prolongs PUL case length but does not appear to have an adverse impact on patient outcomes.
Aged
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Humans
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Internship and Residency/statistics & numerical data*
;
Male
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Middle Aged
;
Prostate/surgery*
;
Prostatic Hyperplasia/surgery*
;
Quality of Life/psychology*
;
Retrospective Studies
;
Treatment Outcome
;
Ureteroscopy/statistics & numerical data*
9.Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig.
Philip D BARDWELL ; Matthew M STARON ; Junjian LIU ; Qingfeng TAO ; Susanne SCESNEY ; Gail BUKOFZER ; Luis E RODRIGUEZ ; Chee-Ho CHOI ; Jennifer WANG ; Qing CHANG ; Feng DONG ; Cherrie DONAWHO ; Jieyi WANG ; Christine M GRINNELL ; Edit TARCSA ; Charles HUTCHINS ; Tariq GHAYUR ; Jijie GU
Protein & Cell 2018;9(1):121-129
Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
Animals
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Antibodies, Bispecific
;
immunology
;
Antibodies, Monoclonal
;
immunology
;
pharmacokinetics
;
CD3 Complex
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metabolism
;
Cell Line, Tumor
;
Cytotoxicity, Immunologic
;
ErbB Receptors
;
metabolism
;
Female
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Humans
;
Lymphocyte Activation
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immunology
;
Mice, SCID
;
Neoplasms
;
immunology
;
pathology
;
Rats, Sprague-Dawley
;
T-Lymphocytes, Cytotoxic
;
immunology
10.Adsorptive hemofiltration for sepsis management: expert recommendations based on the Asia Pacific experience.
Ling ZHANG ; Matthew COVE ; Binh G NGUYEN ; Nuttha LUMLERTGUL ; Kartik GANESH ; Alfred CHAN ; Giang T H BUI ; Chunwen GUO ; Junhua LI ; Songqiao LIU ; Mian PENG ; Kit W FOONG ; Jian ZHANG ; Minmin WANG ; Jacques GOLDSTEIN ; Kai HARENSKI
Chinese Medical Journal 2021;134(18):2258-2260