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Mișcă OM, Mișcă LC, Huzum B, Neamţu AA, Cerbu S, Chioibaș DR, Crăiniceanu PZ, Motoc AGM. A Prospective Randomized Pilot Study on the Efficacy of a Dietary Supplementation Regimen of Vitamin E and Selenium for the Prevention of Fluoroquinolone-Induced Tendinopathy. Pharmaceuticals (Basel) 2025; 18:575. [PMID: 40284010 PMCID: PMC12030472 DOI: 10.3390/ph18040575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 04/12/2025] [Accepted: 04/13/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Fluoroquinolone-induced tendinopathy is a clinically significant adverse effect associated with this class of antibiotics, particularly affecting the Achilles tendon. Despite its growing recognition, the precise pathophysiological mechanisms remain incompletely understood, with hypotheses referencing increased matrix metalloproteinase activity, collagen degradation, and oxidative stress. Methods: This prospective randomized pilot study evaluates the potential protective effectiveness of vitamin E and selenium supplementation in mitigating fluoroquinolone-induced tendinopathy. The study was conducted on 25 patients receiving 500 mg/day levofloxacin antibiotherapy, randomly divided into a control group and an experimental group-vitamin E (400 IU/day) and selenium (200 µg/day), oral supplementation for 28 days. Clinical assessment of the pain level through the VAS score and of functionality through the VISA-A score was performed, alongside ultrasound imaging of the Achilles tendon. To assess potential toxicity and ensure adherence to the supplementation protocol, serial biochemical analyses of serum vitamin E and selenium were performed at predetermined intervals. Results: A significant improvement was observed in pain scores (p = 0.0120) and functional outcomes (p = 0.0340) when comparing the control and experimental groups at the three-month follow-up. Ultrasound analysis revealed reduced tendon thickness and neovascularization, supporting structural recovery. Although the incidence of tendinopathy was lower in the interventional group (13.3% vs. 40%), statistical significance was not reached, possibly due to the small sample size. Conclusions: These findings suggest that antioxidant supplementation with vitamin E and selenium may provide a protective effect against fluoroquinolone-induced tendinopathy, warranting further investigation in larger randomized clinical trials.
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Affiliation(s)
- Oana-Maria Mișcă
- Plastic and Reconstructive Surgery Department—Casa Austria, Pius Brînzeu Clinical County Emergency Hospital Timişoara, Liviu Rebreanu Boulevard, No. 156, 300723 Timișoara, Romania; (O.-M.M.); (P.Z.C.)
- Doctoral School Department, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timişoara, Romania;
| | - Liviu-Coriolan Mișcă
- Doctoral School Department, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timişoara, Romania;
- Trauma & Orthopaedics Department, Cork University Hospital, Wilton, T12 DC4A Cork, Ireland
| | - Bogdan Huzum
- Department of Orthopedics and Traumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universității Str., No. 16, 400347 Iasi, Romania
| | - Andreea-Adriana Neamţu
- Department of Pathology, Pius Brînzeu Clinical County Emergency Hospital Timişoara, Liviu Rebreanu Boulevard, No. 156, 300723 Timișoara, Romania
- Department of Toxicology, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania
- Research Centre for Pharmaco-Toxicological Evaluation, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania
| | - Simona Cerbu
- Department of Radiology and Medical Imaging, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania;
| | - Daniel-Raul Chioibaș
- Department IX of Surgery, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania;
| | - Petrișor Zorin Crăiniceanu
- Plastic and Reconstructive Surgery Department—Casa Austria, Pius Brînzeu Clinical County Emergency Hospital Timişoara, Liviu Rebreanu Boulevard, No. 156, 300723 Timișoara, Romania; (O.-M.M.); (P.Z.C.)
- Department X of General Surgery, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania
| | - Andrei Gheorghe Marius Motoc
- Department of Anatomy and Embryology, “Victor Babeș” University of Medicine and Pharmacy of Timișoara, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania;
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Fleming VH, Xu J, Chen X, Hall D, Southwood RL. Risk of Tendon Injury in Patients Treated With Fluoroquinolone (FQ) Versus Non-Fluoroquinolone Antibiotics for Community-Acquired Pneumonia (CAP). Ann Pharmacother 2024; 58:771-780. [PMID: 37946374 DOI: 10.1177/10600280231210275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Fluoroquinolones (FQs) are associated with increased risk of tendon injury but comparative risk versus other antibiotic options for the same indication has yet to be evaluated. OBJECTIVE Describe the incidence (relative risk) of any tendon injury in patients receiving FQ compared with other (non-FQs) antibiotics for treatment of community-acquired pneumonia (CAP). METHODS A retrospective propensity score weighted cohort study was performed to evaluate the association between FQ antibiotics and tendon injury risk at 2 time points (within 1 month and within 6 months of use) compared with non-FQ regimens for treatment of CAP. The evaluation was performed using the CCAE (MarketScan Commercial Claims and Encounters) and COB (Medicare Supplemental and Coordination of Benefits) databases from 2014 to 2020. Patients with ICD (International Classification of Diseases) 9/10 coding for outpatient pneumonia who were >18 years and without history of tendon injury were included. Patients with history of tendon injury, who received multiple antibiotic therapies for recurrent pneumonia, or who received both FQ and non-FQ regimens during the study period were excluded. Propensity score weighting was used to adjust for selection bias due to contributing risk factors, including demographics (age, sex), comorbidities (diabetes mellitus, chronic kidney disease), and concurrent medications (corticosteroids). RESULTS At 1 month, the odds of tendon injury were estimated to be significantly higher (41.9%) in patients receiving FQs compared with those receiving a non-FQ-based regimen (odds ratio [OR] = 1.419, 95% confidence interval [CI] = [1.188-1.698]). The odds of tendon injury were also estimated to be higher (OR = 1.067, 95% CI = [0.975-1.173]) in the FQ population within 180 days, but this effect was not statistically significant. The most frequent sites of tendon injuries were rotator cuff, shoulder, and patellar tendon. CONCLUSIONS AND RELEVANCE Prescribers should recognize the risk of tendon injury within 1 month of FQ use when considering treatment regimens for CAP and use alternative options with lower risk whenever possible.
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Affiliation(s)
| | - Jianing Xu
- Department of Statistics, University of Georgia, Athens, GA, USA
| | - Xianyan Chen
- Department of Statistics, University of Georgia, Athens, GA, USA
| | - Daniel Hall
- Department of Statistics, University of Georgia, Athens, GA, USA
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Čretnik A, Košir R. Incidence of Achilles tendon rupture: 25-year regional analysis with a focus on bilateral ruptures. J Int Med Res 2023; 51:3000605231205179. [PMID: 37976267 PMCID: PMC10657533 DOI: 10.1177/03000605231205179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 09/15/2023] [Indexed: 11/19/2023] Open
Abstract
OBJECTIVE We aimed to fill the research gap regarding the incidence of Achilles tendon rupture (ATR), which is reportedly increasing, as there is a lack of data on the incidence of ATR and no data on bilateral ruptures in our region. METHODS We determined the incidence of complete ATR among 273,485 people during 1991 to 2015. RESULTS In the study period, 524 patients (486 [92.75%] men and 38 [7.25%] women, average age 39.03±10.86 [range 20-83] years, = sex ratio 12.8:1) were treated for ATR in our study area. The average incidence was 7.77 per 100,000 person-years, with an increasing trend until 2008 and peak incidence of 11.33 per 100,000 person-years. Most injuries (67.04%) occurred while performing sports activities. In total, 7 (1.34%) patients (six men [1.23%] and one woman [2.63%]) experienced ruptures on both sides, an average of 5.1 years apart; the average age at the second rupture was 57.71±16.69 (range 39-83) years, with a calculated incidence for bilateral ATR of 0.1 per 100,000 person-years. CONCLUSIONS The incidence of complete ATR in our study region increased gradually between 1991 and 2008, after which it declined. Bilateral ATR during that period was a very rare injury.
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Affiliation(s)
- Andrej Čretnik
- Department of Traumatology, University Clinical Center Maribor, Maribor, Slovenia
| | - Roman Košir
- Department of Traumatology, University Clinical Center Maribor, Maribor, Slovenia
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Garg M, Venugopalan V, Vouri SM, Diaby V, Iovine NM, Park H. Oral fluoroquinolones and risk of aortic aneurysm or dissection: A nationwide population-based propensity score-matched cohort study. Pharmacotherapy 2023; 43:883-893. [PMID: 37381584 DOI: 10.1002/phar.2841] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 04/09/2023] [Accepted: 04/12/2023] [Indexed: 06/30/2023]
Abstract
STUDY OBJECTIVE To investigate risk of aortic aneurysm or dissection in patients using oral fluoroquinolones compared to those using macrolides in real-world clinical practice among a large US general population. DESIGN Retrospective cohort study design. DATA SOURCE MarketScan commercial and Medicare supplemental databases. PATIENTS Adults patients with at least one prescription fill for fluoroquinolone or macrolide antibiotics. INTERVENTION Fluoroquinolone or macrolide antibiotics. MEASUREMENTS AND MAIN RESULTS The primary outcome was estimated incidence of aortic aneurysm or dissection associated with the use of fluoroquinolones compared with macrolides during a 60-day follow-up period in a 1:1 propensity score-matched cohort. We identified 3,174,620 patients (1,587,310 in each group) after 1:1 propensity score matching. Crude incidence of aortic aneurysm or dissection was 1.9 cases per 1000 person-years among fluoroquinolone users and 1.2 cases per 1000 person-years among macrolide users. In multivariable Cox regression, compared with macrolides, the use of fluoroquinolones was associated with an increased risk of aortic aneurysm or dissection (aHR: 1.34; 95% CI: 1.17-1.54). The association was primarily driven by a high incidence of aortic aneurysm cases (95.8%). Results of sensitivity (e.g., fluoroquinolone exposure ranging from 7 to 14 days (aHR: 1.47; 95% CI: 1.26-1.71)) and subgroup analyses (e.g., ciprofloxacin (aHR: 1.26; 95% CI: 1.07-1.49) and levofloxacin (aHR: 1.44; 95% CI: 1.19-1.52)) remained consistent with main findings. CONCLUSIONS Fluoroquinolone use was associated with a 34% increased risk of aortic aneurysm or dissection compared with macrolide use among a general US population.
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Affiliation(s)
- Mahek Garg
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Veena Venugopalan
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Scott M Vouri
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Vakaramoko Diaby
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Nicole M Iovine
- Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Haesuk Park
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
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Douglas-Vail MB, Morley WN, Hajek J. Marine envenomation by a Pacific red octopus in Vancouver, British Columbia. CAN J EMERG MED 2023; 25:638-640. [PMID: 37166680 DOI: 10.1007/s43678-023-00523-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 04/30/2023] [Indexed: 05/12/2023]
Affiliation(s)
- Matthew B Douglas-Vail
- Department of Emergency Medicine, Faculty of Medicine, Diamond Health Care Centre, University of British Columbia, Vancouver, BC, Canada.
| | - William N Morley
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Jan Hajek
- Division of Infectious Diseases, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
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Effect of Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Application in Achilles-Tendon Injury in an Animal Model. Curr Issues Mol Biol 2022; 44:5827-5838. [PMID: 36547057 PMCID: PMC9776895 DOI: 10.3390/cimb44120396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/16/2022] [Accepted: 11/17/2022] [Indexed: 11/24/2022] Open
Abstract
Background: Achilles-tendon rupture prevails as a common tendon pathology. Adipose-derived mesenchymal stem cells (ADMSCs) are multipotent stem cells derived from adipose tissue with attractive regeneration properties; thus, their application in tendinopathies could be beneficial. Methods: Male rabbit ADMSCs were obtained from the falciform ligament according to previously established methods. After tenotomy and suture of the Achilles tendon, 1 × 106 flow-cytometry-characterized male ADMSCs were injected in four female New Zealand white rabbits in the experimental group (ADMSC group), whereas four rabbits were left untreated (lesion group). Confirmation of ADMSC presence in the injured site after 12 weeks was performed with quantitative sex-determining region Y (SRY)-gene RT-PCR. At Week 12, histochemical analysis was performed to evaluate tissue regeneration along with quantitative RT-PCR of collagen I and collagen III mRNA. Results: Presence of male ADMSCs was confirmed at Week 12. No statistically significant differences were found in the histochemical analysis; however, statistically significant differences between ADMSC and lesion group expression of collagen I and collagen III were evidenced, with 36.6% and 24.1% GAPDH-normalized mean expression, respectively, for collagen I (p < 0.05) and 26.3% and 11.9% GAPDH-normalized mean expression, respectively, for collagen III (p < 0.05). The expression ratio between the ADMSC and lesion group was 1.5 and 2.2 for collagen I and collagen III, respectively. Conclusion: Our results make an important contribution to the understanding and effect of ADMSCs in Achilles-tendon rupture.
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Gupta S, Salwan A, Pisulkar GL, Saoji A, Taywade S. Surgical Repair of Achilles Tendon Rupture by Turn-O-Plasty: A Case Report. Cureus 2022; 14:e29058. [PMID: 36249636 PMCID: PMC9554371 DOI: 10.7759/cureus.29058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 09/11/2022] [Indexed: 12/03/2022] Open
Abstract
Achilles tendon rupture has been a difficult problem for surgeons, especially in older patients, since tendon strength and flexibility are significantly diminished compared to young people. The Achilles tendon endures the highest tensile stresses in the body while running, leaping, and skipping, with tensile loads up to 10 times body weight. There are many treatment options for Achilles tendon repair, including open surgery, percutaneous repair, and ultrasound therapy. Open repair has the danger of scar dehiscence owing to poor skin conditions. In contrast, small invasive operations have the risk of sural nerve damage and a higher possibility of re-rupture. The gold standard method or approach is still under question. Plantar flexion in the ankle is primarily a function of the Achilles tendon; hence, post-operative plantar flexion is a significant determinant of the desired result. We present the case of a 57-year-old male farmer suffering from a left Achilles tendon rupture due to trivial trauma. This rupture consisted of a significant defect, present in the watershed area with signs of tendinosis at the insertion of the tendon. The patient was managed surgically by turn-o-plasty and the degenerated insertion site was augmented with the help of a suture disc. This case report focuses on surgical management by turn-o-plasty for significant defects in the Achilles tendon by using a suture disc to augment the defect.
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Shu Y, Zhang Q, He X, Liu Y, Wu P, Chen L. Fluoroquinolone-associated suspected tendonitis and tendon rupture: A pharmacovigilance analysis from 2016 to 2021 based on the FAERS database. Front Pharmacol 2022; 13:990241. [PMID: 36147351 PMCID: PMC9486157 DOI: 10.3389/fphar.2022.990241] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 08/04/2022] [Indexed: 11/17/2022] Open
Abstract
Objective: The objective of this study was to scientifically and systematically explore the association between fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) and tendonitis and tendon rupture through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Disproportionality analysis was used to quantify the signals of fluoroquinolone-associated suspected tendonitis and tendon rupture based on the FAERS data from January 2016 to March 2021. Clinical characteristics, the onset time, oral and intravenous administrations, and the serious outcomes of fluoroquinolone-associated tendonitis and tendon rupture were further analyzed. Results: Out of 35,667 fluoroquinolone-associated adverse events recorded in the FAERS database during the study period, 1,771 tendonitis and 1,018 tendon ruptures induced by fluoroquinolones as the suspected drug were analyzed, with a median age of 49.88–63.87 years. All three fluoroquinolones detected positive signals of tendonitis and tendon rupture in the four methods. Ciprofloxacin had the strongest statistical association with tendonitis with the highest positive signal values (ROR 98.50, PRR 93.25, IC 6.15, and EBGM 76.80), while levofloxacin showed the strongest statistical association with tendon rupture (ROR 76.38, PRR 73.75, IC 5.84, and EBGM 63.89). Compared with ciprofloxacin and levofloxacin, moxifloxacin was relatively weakly associated with tendonitis and tendon rupture. Oral fluoroquinolone-induced tendonitis and tendon rupture had a stronger signal strength than intravenous administration. The majority of fluroquinolone-related suspected tendonitis and tendon rupture tended to occur within a few days or one month. As for the disability rate of tendonitis, ciprofloxacin counted the highest (n = 461, 50.94%), with moxifloxacin the lowest (n = 20, 29.41%). Conclusion: Fluoroquinolone-induced tendonitis and tendon rupture tended to occur early and might result in serious outcomes. Our study provided valuable references for early identification of the risk of fluoroquinolone-induced tendonitis and tendon rupture.
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Affiliation(s)
- Yamin Shu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qilin Zhang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xucheng He
- Department of Pharmacy, Pengzhou Second People’s Hospital, Pengzhou, China
| | - Yanxin Liu
- Department of Pharmacy, Pengzhou People’s Hospital, Pengzhou, China
| | - Pan Wu
- Department of Pharmacy, Chengfei Hospital, Chengdu, China
| | - Li Chen
- Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
- *Correspondence: Li Chen,
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Chang CK, Chien WC, Hsu WF, Chiao HY, Chung CH, Tzeng YS, Huang SW, Ou KL, Wang CC, Chen SJ, Wang DS. Positive Association Between Fluoroquinolone Exposure and Tendon Disorders: A Nationwide Population-Based Cohort Study in Taiwan. Front Pharmacol 2022; 13:814333. [PMID: 35387340 PMCID: PMC8978711 DOI: 10.3389/fphar.2022.814333] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 02/23/2022] [Indexed: 11/24/2022] Open
Abstract
Introduction: Fluoroquinolone exposure is reportedly associated with a higher risk of tendon disorders, tendonitis, or tendon rupture. However, studies in East Asian populations have not confirmed these risks in patients with comorbidities or concomitant medication use. This cohort study was designed to investigate the associations among fluoroquinolone exposure, comorbidities, medication use, and tendon disorders in Taiwan. Materials and Methods: This population-based, nationwide, observational, cohort study used data from the National Health Insurance Research database in Taiwan, a nationwide claims database that covers more than 99% of the Taiwanese population. The study period was from January 2000 to December 2015, and the median follow-up time was 11.05 ± 10.91 years. Patients who were exposed to fluoroquinolones for more than three consecutive days were enrolled, and patients without fluoroquinolone exposure who were matched by age, sex, and index year were enrolled as controls. The associations of comorbidities and concomitant medication use with tendon disorder occurrence were analyzed using Cox regression models. Results: The incidence of tendon disorders were 6.61 and 3.34 per 105 person-years in patients with and without fluoroquinolone exposure, respectively (adjusted hazard ratio, 1.423; 95% confidence interval [1.02,1.87]; p = 0.021). Sensitivity analyses yielded similar results. Patients under 18 and over 60 years with fluoroquinolone exposure; those with chronic kidney disease, diabetes, rheumatologic disease, cardiac disease, lipid disorder, or obesity; and those who concomitantly used statins, aromatase inhibitors, or glucocorticoids, had a significantly higher risk of tendon disorders. Conclusion: The long-term risk of tendon disorders was higher in patients with fluoroquinolone exposure than in those without fluoroquinolone exposure. Clinicians should assess the benefits and risks of fluoroquinolone use in patients at high risk of tendon disorders who require fluoroquinolone administration.
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Affiliation(s)
- Chun-Kai Chang
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.,Department of Surgery, Zouying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Wu-Chien Chien
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.,School of Public Health, National Defense Medical Center, Taipei, Taiwan.,Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Wan-Fu Hsu
- Department of Pediatrics, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Hao-Yu Chiao
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Hsiang Chung
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.,School of Public Health, National Defense Medical Center, Taipei, Taiwan.,Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan
| | - Yuan-Sheng Tzeng
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Shao-Wei Huang
- Department of Pediatrics, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Kuang-Ling Ou
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Chien Wang
- Department of Pediatrics, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Shyi-Jou Chen
- Department of Pediatrics, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Der-Shiun Wang
- Department of Pediatrics, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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St-Jean A, Chateau D, Dahl M, Ernst P, Daneman N, Sketris IS, Zhang J, Marra F, Quail J, Bugden S. Regional variation in the potentially inappropriate first-line use of fluoroquinolones in Canada as a key to antibiotic stewardship? A drug utilization review study. BMC Infect Dis 2021; 21:733. [PMID: 34344348 PMCID: PMC8330086 DOI: 10.1186/s12879-021-06467-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 07/21/2021] [Indexed: 12/02/2022] Open
Abstract
Background Serious adverse effects of fluoroquinolone antibiotics have been described for more than decade. Recently, several drug regulatory agencies have advised restricting their use in milder infections for which other treatments are available, given the potential for disabling and possibly persistent side effects. We aimed to describe variations in fluoroquinolone use for initial treatment of urinary tract infection (UTI), acute bacterial sinusitis (ABS), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the outpatient setting across Canada. Methods Using administrative health data from six provinces, we identified ambulatory visits with a diagnosis of uncomplicated UTI, uncomplicated AECOPD or ABS. Antibiotic exposure was determined by the first antibiotic dispensed within 5 days of the visit. Results We identified 4,303,144 uncomplicated UTI events among 2,170,027 women; the proportion of events treated with fluoroquinolones, mostly ciprofloxacin, varied across provinces, ranging from 18.6% (Saskatchewan) to 51.6% (Alberta). Among 3,467,678 ABS events (2,087,934 patients), between 2.2% (Nova Scotia) and 11.2% (Ontario) were dispensed a fluoroquinolone. For 1,319,128 AECOPD events among 598,347 patients, fluoroquinolones, mostly levofloxacin and moxifloxacin, ranged from 5.8% (Nova Scotia) to 35.6% (Ontario). The proportion of uncomplicated UTI and ABS events treated with fluoroquinolones declined over time, whereas it remained relatively stable for AECOPD. Conclusions Fluoroquinolones were commonly used as first-line therapies for uncomplicated UTI and AECOPD. However, their use varied widely across provinces. Drug insurance formulary criteria and enforcement may be a key to facilitating better antibiotic stewardship and limiting potentially inappropriate first-line use of fluoroquinolones. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06467-z.
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Affiliation(s)
- Audray St-Jean
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada
| | - Dan Chateau
- Manitoba Centre for Health Policy, Department of Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Matthew Dahl
- Manitoba Centre for Health Policy, Department of Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Pierre Ernst
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada
| | - Nick Daneman
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.,Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | - Jianguo Zhang
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Fawziah Marra
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
| | - Jacqueline Quail
- Health Quality Council, Saskatoon, SK, Canada.,Department of Community Health and Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Shawn Bugden
- School of Pharmacy, Health Sciences Centre, Memorial University of Newfoundland, 300 Prince Philip Drive, St John's, NL, A1B 3V6, Canada. .,College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
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Huruba M, Farcas A, Leucuta DC, Bucsa C, Sipos M, Mogosan C. A VigiBase descriptive study of fluoroquinolone induced disabling and potentially permanent musculoskeletal and connective tissue disorders. Sci Rep 2021; 11:14375. [PMID: 34257376 PMCID: PMC8277836 DOI: 10.1038/s41598-021-93763-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 06/14/2021] [Indexed: 11/09/2022] Open
Abstract
Recent drug safety concerns described fluoroquinolone (FQ)-induced serious musculoskeletal reactions. The objective of this study was to characterize reports with FQ-associated disabling musculoskeletal disorders, from VigiBase. The analysis included all FQ-induced musculoskeletal and connective tissue disorders adverse drug reaction (ADR) reports (up to July-2019), (disabling/incapacitating, or recovered/resolved with sequelae or fatal). We described aspects like reporter, suspected FQs, ADRs, associated corticosteroid therapy. We also looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values. A total of 5355 reports with 13,563 ADRs and 5558 FQs were reported. The majority of reports were for patients aged 18-64 (62.67%), and the female gender prevailed (61.76%). Consumers reported almost half (45.99%), with a peak in reporting rates in 2017. Top reported ADRs were arthralgia (16.34%), tendonitis (11.04%), pain in extremity (9.98%), tendon pain (7.63%), and myalgia (7.17%). Top suspected FQs were levofloxacin (50.04%), ciprofloxacin (38.41%), moxifloxacin (5.16%), ofloxacin (3.17%) and norfloxacin (1.01%). For these, FQs-ADR association was supported by the disproportionality analysis. Corticosteroids were associated with about 7% of tendon related reports. The results augment the existing data on FQs safety concerns, specifically their potential effect on the musculoskeletal system.
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Affiliation(s)
- Madalina Huruba
- Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Andreea Farcas
- Drug Information Research Center, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur Street no 6A, Cluj-Napoca, Romania.
| | - Daniel Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Camelia Bucsa
- Drug Information Research Center, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur Street no 6A, Cluj-Napoca, Romania
| | - Mariana Sipos
- Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Cristina Mogosan
- Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.,Drug Information Research Center, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur Street no 6A, Cluj-Napoca, Romania
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12
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Ross RK, Kinlaw AC, Herzog MM, Jonsson Funk M, Gerber JS. Fluoroquinolone Antibiotics and Tendon Injury in Adolescents. Pediatrics 2021; 147:e2020033316. [PMID: 33990459 PMCID: PMC8168605 DOI: 10.1542/peds.2020-033316] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/02/2021] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To estimate the association between fluoroquinolone use and tendon injury in adolescents. METHODS We conducted an active-comparator, new-user cohort study using population-based claims data from 2000 to 2018. We included adolescents (aged 12-18 years) with an outpatient prescription fill for an oral fluoroquinolone or comparator broad-spectrum antibiotic. The primary outcome was Achilles, quadricep, patellar, or tibial tendon rupture identified by diagnosis and procedure codes. Tendinitis was a secondary outcome. We used weighting to adjust for measured confounding and a negative control outcome to assess residual confounding. RESULTS The cohort included 4.4 million adolescents with 7.6 million fills for fluoroquinolone (275 767 fills) or comparator (7 365 684) antibiotics. In the 90 days after the index antibiotic prescription, there were 842 tendon ruptures and 16 750 tendinitis diagnoses (crude rates 0.47 and 9.34 per 1000 person-years, respectively). The weighted 90-day tendon rupture risks were 13.6 per 100 000 fluoroquinolone-treated adolescents and 11.6 per 100 000 comparator-treated adolescents (fluoroquinolone-associated excess risk: 1.9 per 100 000 adolescents; 95% confidence interval -2.6 to 6.4); the corresponding number needed to treat to harm was 52 632. For tendinitis, the weighted 90-day risks were 200.8 per 100 000 fluoroquinolone-treated adolescents and 178.1 per 100 000 comparator-treated adolescents (excess risk: 22.7 per 100 000; 95% confidence interval 4.1 to 41.3); the number needed to treat to harm was 4405. CONCLUSIONS The excess risk of tendon rupture associated with fluoroquinolone treatment was extremely small, and these events were rare. The excess risk of tendinitis associated with fluoroquinolone treatment was also small. Other more common potential adverse drug effects may be more important to consider for treatment decision-making, particularly in adolescents without other risk factors for tendon injury.
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Affiliation(s)
- Rachael K Ross
- Department of Epidemiology, Gillings School of Global Public Health,
| | - Alan C Kinlaw
- Division of Pharmaceutical Outcomes and Policy, School of Pharmacy
- The Cecil G. Sheps Center for Health Services Research, and
| | - Mackenzie M Herzog
- IQVIA, Durham, North Carolina
- Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | | | - Jeffrey S Gerber
- Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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13
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Chinen T, Sasabuchi Y, Matsui H, Yasunaga H. Association Between Third-Generation Fluoroquinolones and Achilles Tendon Rupture: A Self-Controlled Case Series Analysis. Ann Fam Med 2021; 19:212-216. [PMID: 34180840 PMCID: PMC8118488 DOI: 10.1370/afm.2673] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 08/19/2020] [Accepted: 09/01/2020] [Indexed: 11/09/2022] Open
Abstract
PURPOSE We investigated whether use of third-generation fluoroquinolones is associated with occurrence of Achilles tendon rupture using a case series analysis in which patients served as their own control. METHODS We used administrative claims data to identify residents in a single Japanese prefecture who were enrolled in National Health Insurance and Elderly Health Insurance from April 2012 to March 2017 and experienced Achilles tendon rupture after receiving an antibiotic prescription. Antibiotics were categorized into 3 groups: first- and second-generation fluoroquinolones, third-generation fluoroquinolones, and nonfluoroquinolones. We used a conditional Poisson regression model to estimate the incidence rate ratio (IRR) of Achilles tendon rupture during the antibiotic exposure period relative to the nonexposure period for each patient. An exposure period was defined as 30 days from start of the prescription. RESULTS Analyses were based on 504 patients with Achilles tendon rupture who had received antibiotic prescriptions. Risk of rupture was not significantly elevated during exposure to third-generation fluoroquinolones (IRR = 1.05; 95% CI, 0.33-3.37) and nonfluoroquinolones (IRR = 1.08; 95% CI, 0.80-1.47). In contrast, risk was significantly elevated during exposure to first- and second-generation fluoroquinolones (IRR = 2.94; 95% CI, 1.90-4.54). Findings were similar across subgroups stratified by sex and by recent corticosteroid use. CONCLUSIONS Our analysis showed that third-generation fluoroquinolone use was not associated with an increased risk of Achilles tendon rupture. These antibiotics may be a safer option for patients in whom this risk is elevated, such as athletes.
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Affiliation(s)
- Takashi Chinen
- Department of Clinical Oncology, Jichi Medical University, Tochigi, Japan .,Data Science Center, Jichi Medical University, Tochigi, Japan
| | | | - Hiroki Matsui
- Data Science Center, Jichi Medical University, Tochigi, Japan.,Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Hideo Yasunaga
- Data Science Center, Jichi Medical University, Tochigi, Japan.,Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
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14
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Briones-Figueroa A, Sifuentes-Giraldo WA, Morell-Hita JL, Vázquez-Díaz M. Achilles Tendon Rupture Associated with the Use of Fluoroquinolones in Patients Over 60 Years of AGE: Experience From a Single Tertiary Centre. REUMATOLOGIA CLINICA 2021; 17:141-143. [PMID: 31672507 DOI: 10.1016/j.reuma.2019.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/26/2019] [Accepted: 08/07/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Fluoroquinolones have been associated with increased risk of tendinopathy and Achilles tendon rupture (ATR), especially in patients over 60 years of age. METHODS A retrospective study was carried out including patients over 60 years of age with ATR attended in our centre over the period 2000-2017. RESULTS We identified 44 patients with RTA, of whom 18% (8/44) had been previously treated with fluoroquinolones, with a mean age at diagnosis of ATR of 77.37 years and concomitant corticotherapy in 4 of them. In 7patients, the rupture was spontaneous and all required surgical management. A significantly higher frequency of smoking, concomitant corticotherapy and spontaneous ruptures were found in the group treated with fluoroquinolones. CONCLUSIONS ATR is an adverse event that can occur in patients over 60 years of age treated with fluoroquinolones, so an adequate risk-benefit assessment should be carried out in this population, especially in the presence of associated risk factors.
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Affiliation(s)
| | - Walter Alberto Sifuentes-Giraldo
- Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, España; Instituto Ramón y Cajal de Investigación Sanitaria (IRyCIS), Madrid, España
| | | | - Mónica Vázquez-Díaz
- Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, España
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15
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She G, Teng Q, Li J, Zheng X, Chen L, Hou H. Comparing Surgical and Conservative Treatment on Achilles Tendon Rupture: A Comprehensive Meta-Analysis of RCTs. Front Surg 2021; 8:607743. [PMID: 33681281 PMCID: PMC7931800 DOI: 10.3389/fsurg.2021.607743] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 01/11/2021] [Indexed: 12/28/2022] Open
Abstract
Background: The Achilles tendon is the strongest tendon in human and is frequently injured, mainly in the young to middle age active population. Increasing incidence of Achilles tendon rupture (ATR) is still reported in several studies. Surgical repair and conservative treatment are two major management strategies widely adopted in ATR patients, but the consensus of the optimal treatment strategy is still debated. We aimed at thoroughly reviewing the ATR topic with additional assessments and performed a most comprehensive meta-analysis of randomized controlled trials (RCTs). Method: We comprehensively searched PubMed, Embase, Cochrane, and ClinicalTrial.gov and retrieved all RCTs comparing surgical and conservative treatment on ATR for further analysis. Two independent reviewers performed data extraction and random effect model was adopted when I 2 > 50%, with data presentation of risk ratio, risk difference, or mean difference and 95% confidence interval. Results: A total of 13 RCTs were included in this meta-analysis. A significant difference was observed in re-rupture, complication rate, adhesion to the underlying tendon, sural nerve injury, and superficial infection. A substantial reduction in re-rupture rate could be observed for surgical treatment while the complication rate was higher compared with conservative treatment. Conclusion: Surgical treatment revealed significance in reducing the re-rupture rate but was associated with a higher complication rate, while conservative treatment showed similar outcomes with a lower complication rate. Collectively, we recommend conservative treatment if patients' status and expectations are suitable, but surgeon and physician discretion is also crucial in decision making.
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Affiliation(s)
- Guorong She
- Department of Sport Medicine, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Qiang Teng
- Department of Sport Medicine, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jieruo Li
- Department of Sport Medicine, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiaofei Zheng
- Department of Sport Medicine, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Lin Chen
- Drug Clinical Trial Institution, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Huige Hou
- Department of Sport Medicine, First Affiliated Hospital of Jinan University, Guangzhou, China
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16
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Baik S, Lau J, Huser V, McDonald CJ. Association between tendon ruptures and use of fluoroquinolone, and other oral antibiotics: a 10-year retrospective study of 1 million US senior Medicare beneficiaries. BMJ Open 2020; 10:e034844. [PMID: 33371012 PMCID: PMC7754651 DOI: 10.1136/bmjopen-2019-034844] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
OBJECTIVES To assess the association of fluoroquinolone use with tendon ruptures compared with no fluoroquinolone and that of the four most commonly prescribed non-fluoroquinolone antibiotics in the USA. DESIGN Retrospective observational study. SETTING US seniors enrolled in the federal old-age, survivor's insurance programme. PARTICIPANTS 1 009 925 Medicare fee-for-service beneficiaries and their inpatient, outpatient, prescription drug records were used. INTERVENTIONS Seven oral antibiotics, fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) and amoxicillin, amoxicillin-clavulanate, azithromycin and cephalexin. PRIMARY AND SECONDARY OUTCOME MEASURES All tendon ruptures combined, and three types of tendon ruptures by anatomic site, Achilles tendon rupture, rupture of rotator cuff and other tendon ruptures occurred in 2007-2016. RESULTS Of three fluoroquinolones, only levofloxacin exhibited a significant increased risk of tendon ruptures-16% (HR=1.16; 95% CI 1.06 to 1.28), and 120% (HR=2.20; 95% CI 1.50 to 3.24) for rotator cuff and Achilles tendon rupture, respectively, in the ≤30 days window. Ciprofloxacin (HR=0.96; 95% CI 0.89 to 1.03) and moxifloxacin (HR=0.59; 95% CI 0.37 to 0.93) exhibited no increased risk of tendon ruptures combined.Among the non-fluoroquinolone antibiotics, cephalexin exhibited increased risk of combined tendon ruptures (HR=1.31; 95% CI 1.22 to 1.41) and modest to large risks across all anatomic rupture sites (HRs 1.19-1.93) at ≤30 days window. Notably, the risk of levofloxacin never exceeded the risk of the non-fluoroquinolone, cephalexin in any comparison. CONCLUSIONS In our study, fluoroquinolones as a class were not associated with the increased risk of tendon ruptures. Neither ciprofloxacin nor moxifloxacin exhibited any risk for tendon ruptures. Levofloxacin did exhibit significant increased risk. Cephalexin with no reported effect on metalloprotease activity had an equal or greater risk than levofloxacin; so we question whether metalloprotease activity has any relevance to observed associations with tendon rupture. Confounding by indication bias may be more relevant and should be given more consideration as explanation for significant associations in observational studies of tendon rupture.
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Affiliation(s)
- Seo Baik
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland, USA
| | - Jason Lau
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland, USA
| | - Vojtech Huser
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland, USA
| | - Clement J McDonald
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, Bethesda, Maryland, USA
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17
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Reda Y, Farouk A, Abdelmonem I, El Shazly OA. Surgical versus non-surgical treatment for acute Achilles' tendon rupture. A systematic review of literature and meta-analysis. Foot Ankle Surg 2020; 26:280-288. [PMID: 31027878 DOI: 10.1016/j.fas.2019.03.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 03/19/2019] [Accepted: 03/27/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Achilles' tendon injury affect 31.17 per 100,000 yearly, it has a major impact on quality of life of affected patients, mostly active young individuals. Different management options exist ranging from conservative treatment, to operative repair either open or percutaneous repair. No consensus has been reached on which treatment modality is preferred for each patient. In this study we systematically reviewed the literature for available evidence regarding management of acute Achilles' tendon rupture. METHODS This systematic review consisted of 9 studies, including a systematic search of literature (PubMed, SCOPUS, and The Cochrane Library), selection of studies, extraction of study characteristics, assessment of methodological quality and bias and extraction of data on clinical outcomes and their comparisons between different surgical groups. RESULTS A total of 9 studies were included, 822 patients were extracted from the included studies. Of the 822 patients, 415 (50.4%) had undergone surgical intervention and 407 (49.6%) had received non-surgical treatment. The minimum follow-up duration was 12 months. The left Achilles' tendon was relatively more prone to rupture. The interval from injury to treatment was within 2 to 14 days. Five 5 different surgical techniques were used; end to end, modified Kessler, augmented repair, Krackow type and interrupted circumferential stitch. Operative repair was found to significantly decrease rupture rate (Risk Ratio of 0.36, 95% CI 0.21-0.64; P = 0.0005) with higher risk of wound complications. No statistically significant difference between the two groups in functional outcome scores and range of motion. CONCLUSION We concluded that surgical technique lowers the risk of rerupture rate but associated with higher complication rate which can be reduced by using the minimally invasive techniques. Multicenter randomized clinical trials are needed to obtain a high-quality level of evidence for the comparison between the different modified surgical techniques and the gap effect on making different decision of managements.
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Affiliation(s)
- Yasser Reda
- Department of orthopedic surgeries and traumatology, Ain Shams University, Egypt.
| | - Amr Farouk
- Department of orthopedic surgeries and traumatology, Ain Shams University, Egypt
| | - Ibrahim Abdelmonem
- Department of orthopedic surgeries and traumatology, Ain Shams University, Egypt
| | - Ossama A El Shazly
- Department of orthopedic surgeries and traumatology, Ain Shams University, Egypt
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18
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Karabeg R, Veljovic F, Voloder A, Becirbegovic S, Jahic D, Burak S, Begic E, Masic I. A Mathematical Model of Achilles Tendon Overload During Jump Shot. Med Arch 2019; 73:228-233. [PMID: 31762555 PMCID: PMC6853749 DOI: 10.5455/medarh.2019.73.228-233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Introduction Achilles tendon injuries usually occur with abrupt movements at the level of the ankle and foot, and the consequence is the overload of the Achilles tendon. Aim Examine the Achilles tendon load as a function of the landing angle, and find the critical point at which the tendon overload begins and when a further increase in the landing angle can lead to rupture. Methods The study has a prospective character. The input data represent the anthropometric values of the respondents, who are professional basketball players in the senior national team of Bosnia and Herzegovina and were processed in the CATIA v5-6 software solution. Software data processing analyzed the landing angles and the transfer of force to the Achilles tendon. The end result is a regression curve, which projects the angle at which the Achilles tendon is overloaded, and indicates an increased risk of possible injury to the tendon itself. Results The onset of overloading starts at an angle of 32.28° and at an angle of 35.75° the overloaded load occurs, indicating the need for the subject to change the position of the foot to prevent damage to the tendon itself. Conclusion An angle of 35.75° is the critical point at which the Achilles tendons are overloaded at the very landing. Prevention of injury should go in the direction of practicing the feet for a particular position at the time of the landing, and in the direction to develop adequate footwear that would mitigate the angle at the landing.
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Affiliation(s)
- Reuf Karabeg
- Private Clinic «Karabeg», Sarajevo, Bosnia and Herzegovina
| | - Fikret Veljovic
- Faculty of Mechanical Engineering, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Avdo Voloder
- Faculty of Mechanical Engineering, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | | | - Dzenan Jahic
- Faculty of Sport and Physical Education, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Senad Burak
- Faculty of Mechanical Engineering, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Edin Begic
- Department of Cardiology, General Hospital "Prim.dr. Abdulah Nakas", Sarajevo, Bosnia and Herzegovina
| | - Izet Masic
- Academy of Medical Sciences of Bosnia and Herzegovina, Sarajevo, Bosnia and Herzegovina
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Cheng SL, Wu RG, Chuang YC, Perng WC, Tsao SM, Chang YT, Chang LW, Hsu MC. Integrated safety summary of phase II and III studies comparing oral nemonoxacin and levofloxacin in community-acquired pneumonia. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2019; 52:743-751. [DOI: 10.1016/j.jmii.2018.11.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 10/19/2018] [Accepted: 11/14/2018] [Indexed: 11/27/2022]
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20
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Wosinska L, Cotter PD, O'Sullivan O, Guinane C. The Potential Impact of Probiotics on the Gut Microbiome of Athletes. Nutrients 2019; 11:E2270. [PMID: 31546638 PMCID: PMC6835687 DOI: 10.3390/nu11102270] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 09/05/2019] [Accepted: 09/19/2019] [Indexed: 12/19/2022] Open
Abstract
There is accumulating evidence that physical fitness influences the gut microbiome and as a result, promotes health. Indeed, exercise-induced alterations in the gut microbiome can influence health parameters crucial to athletic performance, specifically, immune function, lower susceptibility to infection, inflammatory response and tissue repair. Consequently, maintenance of a healthy gut microbiome is essential for an athlete's health, training and performance. This review explores the effect of exercise on the microbiome while also investigating the effect of probiotics on various potential consequences associated with over-training in athletes, as well as their associated health benefits.
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Affiliation(s)
- Laura Wosinska
- Department of Biological Sciences, Cork Institute of Technology, Bishopstown, T12 P928 Cork, Ireland.
- Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996 Cork, Ireland.
- APC Microbiome Ireland, T12 YT20 Cork, Ireland.
| | - Paul D Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996 Cork, Ireland.
- APC Microbiome Ireland, T12 YT20 Cork, Ireland.
| | - Orla O'Sullivan
- Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996 Cork, Ireland.
- APC Microbiome Ireland, T12 YT20 Cork, Ireland.
| | - Caitriona Guinane
- Department of Biological Sciences, Cork Institute of Technology, Bishopstown, T12 P928 Cork, Ireland.
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21
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Yu X, Jiang DS, Wang J, Wang R, Chen T, Wang K, Cao S, Wei X. Fluoroquinolone Use and the Risk of Collagen-Associated Adverse Events: A Systematic Review and Meta-Analysis. Drug Saf 2019; 42:1025-1033. [PMID: 31077091 DOI: 10.1007/s40264-019-00828-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION It has been suggested that fluoroquinolone antibiotics increase the risk of developing collagen-associated adverse events such as aortic dissection and aortic aneurysm. These are life-threatening emergencies that need to be prevented. OBJECTIVES We performed this systematic review to clarify the association between fluoroquinolones and three collagen-associated adverse events: aortic aneurysm or aortic dissection, retinal detachment, and tendon disorders. METHODS We searched PubMed, Embase, and Scopus for observational studies up to January 2019. Cohort and case-control studies were included if they reported data on the risk of collagen-related adverse events associated with fluoroquinolone exposure versus no exposure. We assessed the quality of the included studies using the Newcastle-Ottawa Scale. Effect statistics were pooled using random-effects models. Sensitivity and subgroup analyses were performed to identify any source of heterogeneity. RESULTS After screening 2729 citations, we included 22 observational studies (12 cohort studies and ten case-control studies) with 19,207,552 participants. Current use of fluoroquinolones was significantly associated with aortic aneurysm and aortic dissection (odds ratio [OR] 2.20; 95% confidence interval [CI] 1.92-2.52), tendon disorders (OR 1.89; 95% CI 1.53-2.33), and retinal detachment (sensitivity analysis, OR 1.25; 95% CI 1.01-1.53). Past fluoroquinolone use (> 30 and ≤ 365 days) was associated with retinal detachment (OR 1.27; 95% CI 1.09-1.47). CONCLUSIONS Fluoroquinolone use incurs a risk of developing three collagen-associated diseases (aortic aneurysm or aortic dissection, retinal detachment, and tendon disorders). Patients at an increased risk of collagen-associated diseases should not use fluoroquinolones unless no other options are available.
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Affiliation(s)
- Xinyu Yu
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ding-Sheng Jiang
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China
- NHC Key Laboratory of Organ Transplantation, Wuhan, China
- Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
| | - Jing Wang
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Rui Wang
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Taiqiang Chen
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Kan Wang
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Shiyi Cao
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiang Wei
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China.
- NHC Key Laboratory of Organ Transplantation, Wuhan, China.
- Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
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22
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Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis. Eur J Clin Pharmacol 2019; 75:1431-1443. [DOI: 10.1007/s00228-019-02713-1] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 06/25/2019] [Indexed: 01/06/2023]
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Persson R, Jick S. Clinical implications of the association between fluoroquinolones and tendon rupture: The magnitude of the effect with and without corticosteroids. Br J Clin Pharmacol 2019; 85:949-959. [PMID: 30682225 DOI: 10.1111/bcp.13879] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/16/2019] [Accepted: 01/22/2019] [Indexed: 11/30/2022] Open
Abstract
AIMS To estimate the relative, absolute and attributable risk of non-traumatic tendon rupture, at various sites, associated with use of fluoroquinolones, with and without concomitant corticosteroids. METHODS We conducted cohort and nested case-control studies among fluoroquinolone users in the United Kingdom Clinical Practice Research Datalink Gold. We estimated the excess risk (cohort analysis) and odds ratios (ORs) (case control) of tendon rupture by fluoroquinolone (current, recent and past use versus unexposed) and corticosteroid (current versus unexposed) use. RESULTS Among 740 926 patients with a fluoroquinolone prescription, 3957 cases of tendon rupture were identified. The excess risk due to current fluoroquinolone use was low: any tendon rupture 3.73 (95% confidence interval, CI, 2.08-5.39) per 10 000 person-years (PY) and Achilles tendon rupture 2.91 (1.71-4.11) per 10 000 PY. The excess risk of any tendon rupture was much higher for current concomitant fluoroquinolone and corticosteroid use versus corticosteroids alone: 21.2 (11.3-31.2) per 10 000 PY. In the case-control, OR (95% CI) among current fluoroquinolone users versus unexposed patients was elevated: any tendon rupture 1.60 (1.22-2.09), Achilles tendon 2.71 (1.76-4.17) and bicep tendon 1.53 (0.85-2.73). The risk of any tendon rupture was higher among women (OR 2.27 [1.54-3.34]), patients aged 60+ (OR 2.42 [1.74-3.37]), and concomitant corticosteroid use (OR 6.64 [3.99-11.1]). CONCLUSIONS Fluoroquinolones increase the risk of Achilles tendon rupture and, to a lesser extent, bicep tendon rupture, but the attributable risk is low. The risk is materially increased with concomitant use of corticosteroids.
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Affiliation(s)
- Rebecca Persson
- Boston Collaborative Drug Surveillance Program, 11 Muzzey Street, Lexington, MA, USA
| | - Susan Jick
- Boston Collaborative Drug Surveillance Program, 11 Muzzey Street, Lexington, MA, USA.,Boston University School of Public Health, 715 Albany Street, The Talbot Building, T3E & T4E, Boston, MA, USA
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Morales DR, Slattery J, Pacurariu A, Pinheiro L, McGettigan P, Kurz X. Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy: Population-Based Nested Case-Control Study. Clin Drug Investig 2019; 39:205-213. [PMID: 30465300 PMCID: PMC6394638 DOI: 10.1007/s40261-018-0729-y] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND AND OBJECTIVE Tendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure. METHODS The UK Health Improvement Network primary care database was used to perform a nested case-control study measuring the association between fluoroquinolone exposure and tendon rupture. Adults with tendon rupture were matched on age, sex, general practice and calendar time to four controls selected from a cohort prescribed systemic fluoroquinolone or co-amoxiclav antibiotics. The relative and absolute risk of tendon rupture with fluoroquinolone exposure was calculated. RESULTS Current fluoroquinolone exposure was associated with an increased risk of any tendon rupture (adjusted incidence rate ratio [aIRR] 1.61, 95% CI 1.25-2.09) and Achilles tendon rupture (aIRR 3.14, 95% CI 2.11-4.65) that persisted for 60 days. Risk increased with cumulative exposure and was greatest when co-prescribed with oral corticosteroids (aIRR 19.36, 95% CI 7.78-48.19 for Achilles tendon rupture). The adjusted rate difference (aRD) with fluoroquinolone exposure was 2.9 and 2.1 per 10,000 patients for any and Achilles tendon rupture, respectively, and was greatest in people aged ≥ 60 years prescribed concomitant oral corticosteroid therapy (aDR 19.6 for any tendon and 6.6 Achilles tendon rupture per 10,000). No association was seen with co-amoxiclav or statin exposure, or with biceps or other tendon ruptures. CONCLUSIONS Risk of tendon rupture with fluoroquinolones depends on timing, cumulative dose and concomitant exposure to oral corticosteroids. Absolute risk significantly varied by age and concomitant corticosteroid exposure, affecting elderly patients the greatest.
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Affiliation(s)
- Daniel R Morales
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF, UK.
| | - Jim Slattery
- Pharmacovigilance and Epidemiology Department, European Medicines Agency, London, UK
| | - Alexandra Pacurariu
- Pharmacovigilance and Epidemiology Department, European Medicines Agency, London, UK
| | - Luis Pinheiro
- Pharmacovigilance and Epidemiology Department, European Medicines Agency, London, UK
| | - Patricia McGettigan
- Pharmacovigilance and Epidemiology Department, European Medicines Agency, London, UK
- William Harvey Research Institute, Queen Mary University of London, London, UK
| | - Xavier Kurz
- Pharmacovigilance and Epidemiology Department, European Medicines Agency, London, UK
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25
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Indications for Systemic Fluoroquinolone Therapy in Europe and Prevalence of Primary-Care Prescribing in France, Germany and the UK: Descriptive Population-Based Study. Clin Drug Investig 2018; 38:927-933. [DOI: 10.1007/s40261-018-0684-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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26
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Jupiter DC, Fang X, Ashmore Z, Shibuya N, Mehta HB. The Relative Risk of Achilles Tendon Injury in Patients Taking Quinolones. Pharmacotherapy 2018; 38:878-887. [PMID: 29972705 DOI: 10.1002/phar.2162] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE To examine the association between quinolone use and Achilles tendon injury, comparing well-matched cohorts of users of quinolone and nonquinolone antibiotics, and well-matched cohorts of quinolone users and patients not using any nonquinolone antibiotics. PATIENTS AND METHODS This retrospective cohort study used Clinformatics data from 2008-2014. Using the propensity score, we matched quinolone users with other antibiotic users and quinolone users with nonusers. The primary outcome was Achilles tendon injury within 6 months. Bivariate analyses determined risk factors for Achilles tendon injury, and conditional logistic regression assessed the impact of quinolone use on these injuries. RESULTS A total of 716,522 fluoroquinolone users were matched with other antibiotic users, and 645,034 fluoroquinolone users were matched with nonusers. Rates of Achilles tendon injury were less than 0.5% in all groups. Quinolone use increased the risk of Achilles tendon injury compared with other antibiotic users (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.17-1.31) and nonusers (OR 1.54, 95% CI 1.44-1.64). Interaction with age did not significantly impact the relationship between quinolone use and Achilles injury; however, older quinolone users had a slightly higher relative risk of injury than nonusers versus younger patients. Furthermore, the youngest group of patients had similarly elevated relative risk for injury with quinolone use as did the elderly. CONCLUSION Although quinolone use increases the risk of Achilles tendon injury, the absolute risk increase is minimal, especially when compared with similar morbidity patients taking other nonquinolone antibiotics. In relatively healthy populations, such as the one studied here, quinolone use may not make a clinically significant contribution to risk of Achilles tendon injury, at any age range, among those in need of such drugs.
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Affiliation(s)
- Daniel C Jupiter
- Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas
| | - Xiao Fang
- Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas
| | - Zachary Ashmore
- School of Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Naohiro Shibuya
- Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Round Rock, Texas.,Section of Podiatry, Department of Surgery, Central Texas Veterans Affairs Health Care System, Temple, Texas.,Department of Surgery, Baylor Scott& White Health, Temple, Texas
| | - Hemalkumar B Mehta
- Department of Surgery, University of Texas Medical Branch, Galveston, Texas
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27
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Humbyrd CJ, Bae S, Kucirka LM, Segev DL. Incidence, Risk Factors, and Treatment of Achilles Tendon Rupture in Patients With End-Stage Renal Disease. Foot Ankle Int 2018; 39:821-828. [PMID: 29582683 PMCID: PMC6023765 DOI: 10.1177/1071100718762089] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Dialysis-dependent patients and kidney transplant recipients may be at increased risk for Achilles tendon rupture (ATR). METHODS We studied Medicare patients with end-stage renal disease (ESRD) from 1999 through 2013. Patients were categorized as waitlisted for a transplant, not waitlisted, or received a transplant. We performed multivariate negative binomial regression using demographic characteristics, comorbidities, and year of study entry to estimate adjusted incidence rate ratios (aIRRs), identify ATR risk factors, and determine treatment patterns and outcomes. RESULTS We identified 1091 ATRs (incidence, 3.80/10 000 person-years; 95% confidence interval [CI], 3.58-4.03). Compared with transplant recipients, nonwaitlisted patients had a lower incidence (aIRR, 0.44; 95% CI, 0.37-0.53), and waitlisted patients had a similar incidence (aIRR, 0.94; 95% CI, 0.78-1.12) of ATR. ATR incidence was higher among patients taking fluoroquinolones (aIRR, 1.65; 95% CI, 1.32-1.84) and corticosteroids (aIRR, 1.72; 95% CI, 1.44-2.05) compared with those who did not. Patients with ATR were younger, had higher mean body mass index, and had fewer comorbidities than patients without ATR. Seventeen percent of patients received operative treatment within 14 days of ATR diagnosis. The 30-day cumulative incidence of operative site infections was 6.5%. CONCLUSION The incidence of ATR was higher among transplant recipients and waitlisted patients compared with nonwaitlisted patients. Younger age, higher body mass index, fewer comorbidities, fluoroquinolone use, and corticosteroid use were risk factors for ATR. Patients were more likely to receive nonoperative than operative treatment for ATR. Those who underwent operative treatment had a low incidence of operative site infection. LEVEL OF EVIDENCE Prognostic level III, comparative study.
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Affiliation(s)
- Casey Jo Humbyrd
- Department of Orthopaedic Surgery, The Johns Hopkins School of Medicine, Baltimore, MD
| | - Sunjae Bae
- Department of Surgery, The Johns Hopkins School of Medicine, Baltimore, MD,Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, MD
| | - Lauren M. Kucirka
- Department of Surgery, The Johns Hopkins School of Medicine, Baltimore, MD
| | - Dorry L. Segev
- Department of Surgery, The Johns Hopkins School of Medicine, Baltimore, MD,Department of Epidemiology, The Johns Hopkins School of Public Health, Baltimore, MD
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Rozis M, Benetos IS, Karampinas P, Polyzois V, Vlamis J, Pneumaticos SG. Outcome of Percutaneous Fixation of Acute Achilles Tendon Ruptures. Foot Ankle Int 2018. [PMID: 29528724 DOI: 10.1177/1071100718757971] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Conservative treatment of an acute Achilles rupture remains a viable and acceptable option as does surgical fixation, with open and percutaneous repair consisting the main operative techniques. The purpose of this study was to compare the outcomes and complication rates of open versus percutaneous surgical procedures. METHODS From 2009 to 2016, 131 patients were admitted to our department with clinically and radiologically confirmed acute Achilles tendon ruptures. Of those, 82 patients met our inclusion criteria and were randomized into 2 groups, group A (open repair) and group B (percutaneous suturing). Suture equipment was the same for both groups. All patients followed the same rehabilitation protocol. Functional evaluation was made using American Orthopaedic Ankle & Foot Society (AOFAS) hindfoot and Achilles tendon Total Rupture Score (ATRS) questionnaires at the 12-month follow-up. Ankle range of motion (ROM), return-to-work time, and complication rates were additionally measured. RESULTS Both techniques had similar results regarding complication rates and return-to-work time. The major complication in group A was superficial infection (7%) and skin necrosis (3%), whereas 3 patients in group B developed paresthesias due to sural nerve entrapment. Patients in group B had better AOFAS hindfoot (96/100) and ATRS (95/100) scores, but the difference was not significant. ROM was similar in both groups at the 12-month follow-up. CONCLUSION Percutaneous suturing seems to be a safe and effective technique that offers good functional outcomes and low complication rates in patients with acute Achilles tendon ruptures who elect to have surgery. LEVEL OF EVIDENCE Level II, prospective case series.
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Affiliation(s)
- Meletis Rozis
- 1 3rd Orthopaedic Department, KAT Hospital, University of Athens, Athens, Greece
| | - Ioannis S Benetos
- 1 3rd Orthopaedic Department, KAT Hospital, University of Athens, Athens, Greece
| | | | - Vasilios Polyzois
- 1 3rd Orthopaedic Department, KAT Hospital, University of Athens, Athens, Greece
| | - John Vlamis
- 1 3rd Orthopaedic Department, KAT Hospital, University of Athens, Athens, Greece
| | - Spyros G Pneumaticos
- 1 3rd Orthopaedic Department, KAT Hospital, University of Athens, Athens, Greece
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29
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Bedside Ultrasound Diagnosis of Complete Achilles Tendon Tear in a 25-Year-Old Man with Calf Injury. J Emerg Med 2018; 54:694-696. [PMID: 29627350 DOI: 10.1016/j.jemermed.2018.01.028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 01/05/2018] [Accepted: 01/19/2018] [Indexed: 12/28/2022]
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30
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Fluoroquinolones and the Risk of Achilles Tendon Disorders: Update on a Neglected Complication. Urology 2017; 113:20-25. [PMID: 29074337 DOI: 10.1016/j.urology.2017.10.017] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Revised: 09/09/2017] [Accepted: 10/10/2017] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To evaluate the current evidence and to identify associated risk factors that increase the incidence of this complication. Fluoroquinolone (FQ) has been considered the first-line therapy for uncomplicated urinary infections. FQ has been associated with Achilles tendon disorders, especially during the first month of treatment. METHODS Data sources searched included PubMed, MEDLINE, and Scopus from January 1988 to June 2017. RESULTS A total of 79 articles were used, with ciprofloxacin representing the most common drug. CONCLUSION We found that male gender, advanced age, normal body mass index, chronic renal failure, and concurrent use of corticosteroids increase the risk of Achilles tendon disorders.
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31
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Two Unique Cases of Ciprofloxacin-Associated Avulsion of Ligament and Tendon. Am J Phys Med Rehabil 2017; 97:e33-e36. [PMID: 28857901 DOI: 10.1097/phm.0000000000000816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Ciprofloxacin is recognized to have a deleterious relationship with tendons, particularly Achilles tendinopathy, which makes up most case reports. Tendinopathy seems to occur because of induction of collagen-degrading enzymes causing damage and ischemia of the poorly vascularized regions preventing repair. The focus on the relationship of ciprofloxacin and the Achilles tendon leaves patients on fluoroquinolones with non-Achilles tendinopathy symptoms at risk of misdiagnosis. There have not been any documented instances of ligament damage with ciprofloxacin administration in the literature, although ligament and tendon compositions are similar and should have similar susceptibility. This report includes two cases, one presenting with right lateral thumb pain and a medical history of gastroenteritis treated with ciprofloxacin. Physical examination showed swelling of the right metacarpophalangeal joint and ultrasound confirmed disruption of the radial collateral ligament at insertion on first metacarpal; the second case is of a woman presenting with right hip pain in setting of chronic recurrent diverticulitis treated with ciprofloxacin. She received work-up for lumbar disc disease and spondylosis. After standard therapy with pharmacotherapy and physical therapy for radiculopathy failed, magnetic resonance imaging was performed showing near complete avulsion of the right hamstring tendons from the ischial tuberosity.
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32
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Fang Q, Guo C, Wang Y, Liu Y. The study on interactions between levofloxacin and model proteins by using multi-spectroscopic and molecular docking methods. J Biomol Struct Dyn 2017; 36:2032-2044. [PMID: 28604271 DOI: 10.1080/07391102.2017.1341335] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The interactions of levofloxacin (LEV) with lysozyme (LYZ), trypsin and bovine hemoglobin (BHb) were investigated, respectively, by using multi-spectral techniques and molecular docking in vitro. Fluorescence studies showed that LEV quenched LYZ/trypsin fluorescence in a combined quenching ways and BHb fluorescence in a static quenching with binding constants of .14, .51 and .20 × 105 L mol-1 at 298 K, respectively. The thermodynamic parameters demonstrated that hydrophobic forces, hydrogen bonds, and van der Waals forces played the major role in the binding process. The binding distances between LEV and the inner tryptophan residues of LYZ, trypsin, and BHb were calculated to be 4.04, 3.38, and 4.52 nm, respectively. Furthermore, the results of circular dichroism spectra (CD), UV-vis, and three-dimensional fluorescence spectra indicated that the secondary structures of LYZ, trypsin, and BHb were partially changed by LEV with the α-helix percentage of LYZ-LEV system increased while that of BHb-LEV system was decreased, the β-sheet percentage of trypsin-LEV system increased from 41.3 to 42.9%. UV-vis spectral results showed that the binding interactions could cause conformational and some micro-environmental changes of LYZ, trypsin, and BHb. The results of molecular docking revealed that in LYZ and trypsin systems, LEV bound to the active sites residues GLU 35 and ASP 52 of LYZ and trypsin at the active site SER 195, and in BHb system, LEV was located in the central cavity, which was consistent with the results of synchronous fluorescence experiment. Besides, LEV made the activity of LYZ decrease while the activity of trypsin increased.
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Affiliation(s)
- Qing Fang
- a College of Life and Environmental Sciences, Minzu University of China , Beijing 100081 , China
| | - Chenhui Guo
- a College of Life and Environmental Sciences, Minzu University of China , Beijing 100081 , China
| | - Yirun Wang
- a College of Life and Environmental Sciences, Minzu University of China , Beijing 100081 , China
| | - Ying Liu
- a College of Life and Environmental Sciences, Minzu University of China , Beijing 100081 , China.,b Beijing Engineering Research Center of Food Environment and Public Health, Minzu University of China , Beijing 100081 , China
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Abstract
Non-insertional Achilles tendinopathy is a degenerative condition characterised by pain on activity.Eccentric stretching is the most effective treatment.Surgical treatment is reserved for recalcitrant cases.Minimally-invasive and tendinoscopic treatments are showing promising results. Cite this article: Pearce CJ, Tan A. Non-insertional Achilles tendinopathy. EFORT Open Rev 2016;1:383-390. DOI: 10.1302/2058-5241.1.160024.
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Affiliation(s)
| | - Audrey Tan
- Jurong Health Services Pte Ltd, Singapore
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34
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Abstract
PURPOSE OF REVIEW The purpose of this study is to review the current literature of Achilles tendon injuries, specifically chronic tendinopathy and acute ruptures in regard to etiology, diagnosis, treatment options, and outcomes. RECENT FINDINGS The incidence of Achilles tendon injuries is increasing, but the necessity for surgical intervention is decreasing due to improved conservative therapies, which may provide comparable outcomes without the implied surgical risk. If surgery is undertaken, no difference has been noted between open and minimally invasive techniques. The majority of patients are able to return to pre-injury level of activity, with the elite athlete as an unfortunate exception. Achilles injuries can be devastating injuries, but if addressed early and appropriately, most patients have good self-reported long-term outcomes regardless of the treatment modality implemented. Further research is needed into the etiology, potential preventative measures, and longer-term outcomes of the different treatment options for wide range of Achilles pathology.
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Affiliation(s)
- Anthony C Egger
- Department of Orthopaedic Surgery, The Cleveland Clinic Foundation, 2049 E 100th St, Desk A40, Cleveland, OH, 44195, USA.
| | - Mark J Berkowitz
- Department of Orthopaedic Surgery, The Cleveland Clinic Foundation, 2049 E 100th St, Desk A40, Cleveland, OH, 44195, USA
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Abstract
A shortcut review of the literature was carried out to establish whether the use of fluoroquinolones was associated with an increased risk of tendinopathy in adult patients. 10 trials were found to be directly relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that there is an association between the use of fluoroquinolones and a broad range of tendinopathies.
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36
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Levofloxacin-associated bilateral Achilles’ tendon rupture, in patient with two secondary hip fractures. Eur Geriatr Med 2016. [DOI: 10.1016/j.eurger.2016.03.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Abstract
BACKGROUND Fluoroquinolone antibiotics are commonly used to treat infections and are prescribed by general practitioners, medical specialists and surgeons. Tendon injury has been associated with the use of these medications but the risk associated with newer fluoroquinolones has not been established. OBJECTIVES The aim of this systematic review was to evaluate the evidence from observational studies to determine the strength of the association between fluoroquinolone use and tendinopathy, and to identify risk factors for this complication. METHODS We searched MEDLINE, EMBASE and the Cochrane Collaboration from inception through May 2013 to identify observational studies focused on tendon injury and fluoroquinolones. Studies with original data were selected for inclusion following the PRISMA guidelines. Of the 560 abstracts screened, 16 relevant studies were independently rated by three authors (WW, AS, DC) using the Newcastle-Ottawa Quality Assessment Scale, and assigned a quality score out of 9. High-quality studies (i.e. scored 4.5 or higher) are summarized in detail in this article. Data were independently extracted by two authors (WW, AS). RESULTS Overall, 16 studies were included in our study. Eight were deemed to be of high quality and five specifically evaluated Achilles tendon rupture. In addition, three studies examined Achilles tendinitis, and three included tendon disorders (including any tendon rupture) as an outcome. Results from these studies suggest that individuals exposed to fluoroquinolones are at increased risk for Achilles tendon rupture, particularly within the first month following exposure to the drug (odds ratios ranged from 1.1 to 7.1). One study showed an increased risk of tendon rupture in those over 60 years of age. Five studies stated that individuals taking fluoroquinolones and oral corticosteroids are at increased risk for tendon injury compared with those taking fluoroquinolones alone. Four studies examined the differential effect of a limited number of fluoroquinolones. Ofloxacin had the highest risk of tendon injury in three of the studies. LIMITATIONS Included studies are observational in nature and rely on self-report, which may lead to misclassification or underestimation of tendon injury. CONCLUSIONS Observational studies showed an increased risk of tendon injury, including tendon rupture and tendinitis, with exposure to fluoroquinolone antibiotic therapy. Although this complication appears to be rare, concomitant corticosteroids increase the risk for tendon injury, which varies depending on the fluoroquinolone used.
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38
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Bidell MR, Lodise TP. Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk? Pharmacotherapy 2016; 36:679-93. [DOI: 10.1002/phar.1761] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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39
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Mendes A, Palmer S. A look at assessing Achilles tendinopathy in the community. Br J Community Nurs 2016; 21:315-316. [PMID: 27270201 DOI: 10.12968/bjcn.2016.21.6.315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Affiliation(s)
- Aysha Mendes
- Freelance journalist specialising in health, psychology and nursing
| | - Sarah Palmer
- Disability Analyst, Department for Work and Pensions/Maximus
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40
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Hopkins C, Fu SC, Chua E, Hu X, Rolf C, Mattila VM, Qin L, Yung PSH, Chan KM. Critical review on the socio-economic impact of tendinopathy. Asia Pac J Sports Med Arthrosc Rehabil Technol 2016; 4:9-20. [PMID: 29264258 PMCID: PMC5730665 DOI: 10.1016/j.asmart.2016.01.002] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 01/21/2016] [Accepted: 01/21/2016] [Indexed: 12/16/2022] Open
Abstract
There are currently no studies that determine the total burden that tendinopathy places on patients and society. A systematic search was conducted to understand the impact of tendinopathy. It demonstrated that the current prevalence is underestimated, particularly in active populations, such as athletes and workers. Search results demonstrate that due to the high prevalence, impact on patients' daily lives and the economic impact due to work-loss, treatments are significantly higher than currently observed. A well-accepted definition by medical professionals and the public will improve documentation and increase awareness, in order to better tackle the disease burden.
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Affiliation(s)
- Chelsea Hopkins
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Sai-Chuen Fu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Eldrich Chua
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Xiaorui Hu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Christer Rolf
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Division of Orthopaedics and Biotechnology, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
| | - Ville M. Mattila
- Division of Orthopaedics and Biotechnology, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
- Department of Orthopaedics, Tampere University Hospital, Tampere, Finland
| | - Ling Qin
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Translational Medicine Research and Development Centre, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Patrick Shu-Hang Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Kai-Ming Chan
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Wiseman SP, Beran MC, Warahadpande S, MacDonald JP. Rupture of the Long Head of the Biceps Tendon in a Pediatric Athlete: A Case Report. JBJS Case Connect 2016; 6:e33. [PMID: 29252667 DOI: 10.2106/jbjs.cc.15.00174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
CASE We report a case of an adolescent athlete who sustained an isolated rupture of the long head of the biceps tendon and was subsequently treated with subpectoral biceps tenodesis. CONCLUSION Provided that there is no damage to the rotator cuff, an open biceps tenodesis may be performed in this young patient population with good short-term outcomes and return to full activity.
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Affiliation(s)
- Stephen P Wiseman
- Department of Orthopedic Surgery (S.P.W. and M.C.B.) and Division of Sports Medicine, Department of Pediatrics (J.P.M.), Nationwide Children's Hospital, Columbus, Ohio
| | - Matthew C Beran
- Department of Orthopedic Surgery (S.P.W. and M.C.B.) and Division of Sports Medicine, Department of Pediatrics (J.P.M.), Nationwide Children's Hospital, Columbus, Ohio.,College of Medicine, The Ohio State University, Columbus, Ohio
| | | | - James P MacDonald
- Department of Orthopedic Surgery (S.P.W. and M.C.B.) and Division of Sports Medicine, Department of Pediatrics (J.P.M.), Nationwide Children's Hospital, Columbus, Ohio.,College of Medicine, The Ohio State University, Columbus, Ohio
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Ansari NN, Naghdi S, Hasanvand S, Fakhari Z, Kordi R, Nilsson-Helander K. Cross-cultural adaptation and validation of Persian Achilles tendon Total Rupture Score. Knee Surg Sports Traumatol Arthrosc 2016; 24:1372-1380. [PMID: 26740087 DOI: 10.1007/s00167-015-3977-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 12/22/2015] [Indexed: 02/05/2023]
Abstract
PURPOSE To cross-culturally adapt the Achilles tendon Total Rupture Score (ATRS) to Persian language and to preliminary evaluate the reliability and validity of a Persian ATRS. METHODS A cross-sectional and prospective cohort study was conducted to translate and cross-culturally adapt the ATRS to Persian language (ATRS-Persian) following steps described in guidelines. Thirty patients with total Achilles tendon rupture and 30 healthy subjects participated in this study. Psychometric properties of floor/ceiling effects (responsiveness), internal consistency reliability, test-retest reliability, standard error of measurement (SEM), smallest detectable change (SDC), construct validity, and discriminant validity were tested. Factor analysis was performed to determine the ATRS-Persian structure. RESULTS There were no floor or ceiling effects that indicate the content and responsiveness of ATRS-Persian. Internal consistency was high (Cronbach's α 0.95). Item-total correlations exceeded acceptable standard of 0.3 for the all items (0.58-0.95). The test-retest reliability was excellent [(ICC)agreement 0.98]. SEM and SDC were 3.57 and 9.9, respectively. Construct validity was supported by a significant correlation between the ATRS-Persian total score and the Persian Foot and Ankle Outcome Score (PFAOS) total score and PFAOS subscales (r = 0.55-0.83). The ATRS-Persian significantly discriminated between patients and healthy subjects. Explanatory factor analysis revealed 1 component. CONCLUSION The ATRS was cross-culturally adapted to Persian and demonstrated to be a reliable and valid instrument to measure functional outcomes in Persian patients with Achilles tendon rupture. LEVEL OF EVIDENCE II.
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Affiliation(s)
- Noureddin Nakhostin Ansari
- Department of Physiotherapy, School of Rehabilitation, Tehran University of Medical Sciences, Enghelab Ave, Pitch-e-shemiran, Tehran, 11489, Iran.
| | - Soofia Naghdi
- Department of Physiotherapy, School of Rehabilitation, Tehran University of Medical Sciences, Enghelab Ave, Pitch-e-shemiran, Tehran, 11489, Iran
| | - Sahar Hasanvand
- Department of Physiotherapy, School of Rehabilitation, Tehran University of Medical Sciences, Enghelab Ave, Pitch-e-shemiran, Tehran, 11489, Iran
| | - Zahra Fakhari
- Department of Physiotherapy, School of Rehabilitation, Tehran University of Medical Sciences, Enghelab Ave, Pitch-e-shemiran, Tehran, 11489, Iran
| | - Ramin Kordi
- Sports Medicine Research Centre, Tehran University of Medical Sciences, Tehran, Iran
| | - Katarina Nilsson-Helander
- Department of Orthopaedic, Sahlgrenska Academy, Gothenburg University, Kungsbacka Hospital Tölövägen 5, 434 40, Kungsbacka, Sweden
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Abstract
BACKGROUND The Achilles tendon is the strongest tendon in the human body. The incidence of Achilles tendon ruptures appears to be increasing. OBJECTIVES The aim of this review was to systematically summarize predictors influencing Achilles tendon rupture (ATR) risk. METHODS A systematic literature search was performed of reported determinants influencing the ATR risk. Studies were eligible if there was: (i) description of determinants predicting ATR; (ii) an outcome defined as ATR; (iii) any study design with at least ten adults included with ATR; (iv) use of statistical tests regarding differences between patients with an ATR and healthy controls; (v) a full text article available; (vi) an article written in English, German or Dutch. Quality assessment was done using a standardized criteria set. Best-evidence synthesis was performed. RESULTS We included 31 studies, of which two (6.5%) were considered high-quality studies. Moderate evidence was found for increased ATR risk and decreased fibril size of Achilles tendon. CONCLUSION Based on the results of this systematic review there is moderate evidence that decreased tendon fibril size increases the ATR risk. There is limited evidence for many other factors, some of which are modifiable, such as increased body weight, oral corticosteroid use and quinolone use and living in an urban area, and therefore may be of interest in future studies. Furthermore, these results showed that more high-quality studies are needed for evaluating the determinants influencing the ATR risk.
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Affiliation(s)
- Femke M A P Claessen
- Department of Orthopaedic Surgery, Erasmus MC, University Medical Centre Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands
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Arabyat RM, Raisch DW, McKoy JM, Bennett CL. Fluoroquinolone-associated tendon-rupture: a summary of reports in the Food and Drug Administration’s adverse event reporting system. Expert Opin Drug Saf 2015; 14:1653-60. [DOI: 10.1517/14740338.2015.1085968] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects include renal damage and, strangely, tendinopathies. The pathological mechanisms underlying these toxicities are poorly understood. Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent. We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar concentrations, these antibiotics inhibited jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted to stabilize transcription factor HIF-1α by inhibition of the oxygen-dependent hypoxia-inducible transcription factor prolyl hydroxylation. In dramatic contrast to this prediction, HIF-1α protein was eliminated by FQ treatment. We explored possible mechanisms for this unexpected effect and show that FQ inhibit HIF-1α mRNA translation. Thus, FQ antibiotics induce global epigenetic changes, inhibit collagen maturation, and block HIF-1α accumulation. We suggest that these mechanisms explain the classic renal toxicities and peculiar tendinopathies associated with FQ antibiotics.
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Affiliation(s)
- Sujan Badal
- From the Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905
| | - Yeng F Her
- From the Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905
| | - L James Maher
- From the Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905
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Gulati V, Jaggard M, Al-Nammari SS, Uzoigwe C, Gulati P, Ismail N, Gibbons C, Gupte C. Management of achilles tendon injury: A current concepts systematic review. World J Orthop 2015; 6:380-386. [PMID: 25992315 PMCID: PMC4436906 DOI: 10.5312/wjo.v6.i4.380] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 03/28/2015] [Accepted: 04/20/2015] [Indexed: 02/06/2023] Open
Abstract
Achilles tendon rupture has been on the rise over recent years due to a variety of reasons. It is a debilitating injury with a protracted and sometimes incomplete recovery. Management strategy is a controversial topic and evidence supporting a definite approach is limited. Opinion is divided between surgical repair and conservative immobilisation in conjunction with functional orthoses. A systematic search of the literature was performed. Pubmed, Medline and EmBase databases were searched for Achilles tendon and a variety of synonymous terms. A recent wealth of reporting suggests that conservative regimens with early weight bearing or mobilisation have equivalent or improved rates of re-rupture to operative regimes. The application of dynamic ultrasound assessment of tendon gap may prove crucial in minimising re-rupture and improving outcomes. Studies employing functional assessments have found equivalent function between operative and conservative treatments. However, no specific tests in peak power, push off strength or athletic performance have been reported and whether an advantage in operative treatment exists remains undetermined.
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Guss D, Smith JT, Chiodo CP. Acute Achilles Tendon Rupture: A Critical Analysis Review. JBJS Rev 2015; 3:01874474-201504000-00002. [PMID: 27490254 DOI: 10.2106/jbjs.rvw.n.00015] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Daniel Guss
- MGM Comprehensive Foot and Ankle Center, Department of Orthopaedic Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114
| | - Jeremy T Smith
- Brigham Foot and Ankle Center, Department of Orthopaedic Surgery, Brigham and Women's Faulkner Hospital, 1153 Centre Street, Suite 56, Boston, MA 02130
| | - Christopher P Chiodo
- Brigham Foot and Ankle Center, Department of Orthopaedic Surgery, Brigham and Women's Faulkner Hospital, 1153 Centre Street, Suite 56, Boston, MA 02130
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Bai ZL, Chen Q, Yang SD, Zhang F, Wang HY, Yang DL, Ding WY. Toxic effects of levofloxacin on rat annulus fibrosus cells: an in-vitro study. Med Sci Monit 2014; 20:2205-12. [PMID: 25380657 PMCID: PMC4237079 DOI: 10.12659/msm.892610] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 10/28/2014] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Fluoroquinolones are in wide clinical use as safe and effective antibiotics. Articular cartilage, tendons, and epiphyseal growth plates have been recognized as targets of fluoroquinolone-induced connective tissue toxicity. However, the effects of fluoroquinolones on annulus fibrosus (AF) cells are still unknown. MATERIAL/METHODS The main objective of this study was to investigate the effects of levofloxacin, a typical fluoroquinolone antibiotic drug, on rat AF cells in vitro. Rat annulus fibrosus (RAF) cells were treated with levofloxacin at different concentrations (0, 10, 20, 30, 40, 60, 80, and 90 μg/ml) and were assessed to determine the possible cytotoxic effects of levofloxacin. Inverted phase-contrast microscopy was used to accomplish the morphological observation of apoptosis of treated cells. Western blot and real-time quantitative RT-PCR (qPCR) was used to explore the expression of active caspase-3 and MMP-3. Flow cytometry was used to measure the apoptotic incidences. RESULTS Our study showed that levofloxacin, with concentrations at 30, 60, and 90 μg/ml, induced dose-dependent RAF cell apoptosis and higher expression of caspase-3 and MMP-3. More apoptotic cells were observed by inverted phase-contrast microscopy. Moreover, levofloxacin increased the activity of caspase-3, and it also reduced cell viability with different concentrations ranging from 10 to 80 μg/ml. CONCLUSIONS Our study results suggest that levofloxacin has cytotoxic effects on RAF cells, characterized by enhancing apoptosis and reducing cell viability, and indicate a potential toxic effect of fluoroquinolones on RAF cells.
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Affiliation(s)
- Zhi-Long Bai
- Department of Spinal Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Qian Chen
- Department of Spinal Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Si-Dong Yang
- Department of Spinal Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Feng Zhang
- Department of Rehabilitation Medicine, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Hai-Ying Wang
- Department of Spinal Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Da-Long Yang
- Department of Spinal Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Wen-Yuan Ding
- Department of Spinal Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
- Hebei Provincial Key Laboratory of Orthopedic Biomechanics, Shijiazhuang, Hebei, China
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Abstract
CONTEXT Antibiotics are the mainstay of treatment for bacterial infections in patients of all ages. Athletes who maximally train are at risk for illness and various infections. Routinely used antibiotics have been linked to tendon injuries, cardiac arrhythmias, diarrhea, photosensitivity, cartilage issues, and decreased performance. EVIDENCE ACQUISITION Relevant articles published from 1989 to 2012 obtained through searching MEDLINE and OVID. Also, the Food and Drug Administration website was utilized. STUDY DESIGN Clinical review. LEVEL OF EVIDENCE Level 3. RESULTS The team physician should consider alternative medications in place of the "drug of choice" when adverse drug effects are a concern for an athlete's health or performance. If alternative medications cannot be selected, secondary preventative measures, including sunscreen or probiotics, may be needed. CONCLUSION Physicians choose medications based on a variety of factors to help ensure infection resolution while limiting potential side effects. Extra precautions are indicated when treating athletes with certain antibiotics.
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Affiliation(s)
| | - Matthew Voltz
- Delaware Orthopedic Specialists, Wilmington, Delaware
| | | | - Jeremy Close
- Thomas Jefferson University Hospital, Philadelphia, PA
| | | | - Joshua Okon
- Christiana Care Health System, Wilmington, Delaware
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Consiglio GP, Burden AM, Maclure M, McCarthy L, Cadarette SM. Case-crossover study design in pharmacoepidemiology: systematic review and recommendations. Pharmacoepidemiol Drug Saf 2013; 22:1146-53. [DOI: 10.1002/pds.3508] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 06/20/2013] [Accepted: 07/29/2013] [Indexed: 12/15/2022]
Affiliation(s)
- Giulia P. Consiglio
- Leslie Dan Faculty of Pharmacy; University of Toronto; Toronto Ontario Canada
| | - Andrea M. Burden
- Leslie Dan Faculty of Pharmacy; University of Toronto; Toronto Ontario Canada
| | - Malcolm Maclure
- Department of Anesthesiology, Pharmacology and Therapeutics; University of British Columbia; Vancouver British Columbia Canada
| | - Lisa McCarthy
- Leslie Dan Faculty of Pharmacy; University of Toronto; Toronto Ontario Canada
- Women's College Research Institute; Toronto Ontario Canada
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