OBJECTIVE: To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes. METHODS: The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived. Simulation studies were conducted to evaluate the derived power functions. RESULTS: Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed. The intra-correlation showed a positive correlation with the power of the bioequivalence test. When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval. If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power. Sample size can be calculated through numerical iteration with the derived power functions. CONCLUSION The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.
Administration, Topical ; Clinical Trials as Topic ; methods ; Cross-Over Studies ; Humans ; Models, Theoretical ; Ophthalmic Solutions ; pharmacokinetics ; Sample Size ; Therapeutic Equivalency

PURPOSE: The measurement of heart rate variability (HRV) is a non-invasive method to analyze the balance of the autonomic nervous system. The aim of this study was to compare the changes of HRV and base deficit (BD) during the treatment of trauma patients. METHODS: Forty-three trauma patients with a low injury severity scores (ISS < 24) and negative base excess on admission were included in this study. Based on the BD changes, patients were divided into three groups: 'end pointed' group (n = 13), patients' BDs instantly cleared after primary hydration; 'needs further resuscitation' group (n = 21), patients' BDs did not reach the end point and thus required further hydration or packed red blood cells transfusion; and 'hydration minimal change' group (n = 9), patients' BDs lower than 2.5 mmol/L at the onset of admission and thereafter had minimal change (near normal range). The changes in HRV during fluid resuscitation were detected and compared to BD changes in their arterial blood gases. All data were analysed using the SPSS software Version 15.0. Repeated measures ANOVA was used to determine the changes in HRV, heart rate, blood pressure, and BD among groups. RESULTS: A significant reverse correlation was found between the BD ratio and the HRV ratio (r = -0.562; p = 0.01). The HRV of patients with aggravated BDs after fluid resuscitation was decreased. There was an increase in HRV at the time of BD clearance. A decrease in HRV after primary crystalloid hydration bore a significant connection with the need for an ICU (p = 0.021) and transfusion of packed red blood cells (p < 0.001). CONCLUSION Increase in HRV may be a new non-invasive index for the end point of resuscitation in trauma patients.
Adolescent ; Adult ; Aged ; Autonomic Nervous System ; physiopathology ; Crystalloid Solutions ; administration & dosage ; Fluid Therapy ; Heart Rate ; Humans ; Injury Severity Score ; Middle Aged ; Resuscitation ; methods ; Wounds and Injuries ; diagnosis ; physiopathology ; Young Adult

OBJECTIVETo investigate the efficacy of oral sweet solutions in relieving pain caused by vaccination in infants aged 1 to 12 months.

METHODSRelated databases were searched to find related randomized control trails (RCTs). The quality of these RCTs was evaluated. The Meta analysis was performed using RevMan 5.3.

RESULTSA total of 20 RCTs involving 2 376 infants were included, and quality assessment showed that 6 RCTs had grade A quality and 14 had grade B quality. The Meta analysis showed that compared with sterile water, 25%-75% oral sweet solution significantly reduced crying time (WMD=-21.16, 95%CI -39.66 to -2.77, P<0.05) and the proportion of crying time (the duration of crying /3-minute periods after the injection) (WMD=-13.83, 95%CI -20.88 to -6.78, P<0.01), while the crying time showed no significant difference between the group treated with oral administration of 12% sucrose solution and non-intervention group. Co

ONCLUSIONSOral sweet solution (25%-75%; 2 mL) given 2 minutes before vaccination can effectively relieve the pain caused by vaccination in infants aged 1-12 months.

Crying ; Humans ; Infant ; Pain ; prevention & control ; Solutions ; Sucrose ; administration & dosage ; Vaccination ; adverse effects

Pleural effusion after hepatectomy is associated with significant morbidity and prolonged hospital stays. Several studies have addressed the risk factors for postoperative pleural effusion. However, there are no researches concerning the role of the initial 12-h operative fluid volume. The aim of this study was to evaluate whether the initial 12-h operative fluid volume during liver resection is an independent risk factor for pleural effusion after hepatectomy. In this study, we retrospectively analyzed clinical data of 470 patients consecutively undergoing elective hepatectomy between January 2011 and December 2012. We prospectively collected and retrospectively analyzed baseline and clinical data, including preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were carried out to identify whether the initial 12-h operative fluid volume was an independent risk factor for pleural effusion after hepatectomy. The multivariate analysis identified 2 independent risk factors for pleural effusion: operative time [odds ratio (OR)=10.2] and initial 12-h operative fluid volume (OR=1.0003). Threshold effect analyses revealed that the initial 12 h operative fluid volume was positively correlated with the incidence of pleural effusion when the initial 12-h operative fluid volume exceeded 4636 mL. We conclude that the initial 12-h operative fluid volume during liver resection and operative time are independent risk factors for pleural effusion after hepatectomy. Perioperative intravenous fluids should be restricted properly.
Adult ; Aged ; Female ; Fluid Therapy ; adverse effects ; Hepatectomy ; adverse effects ; methods ; Humans ; Male ; Middle Aged ; Operative Time ; Pleural Effusion ; epidemiology ; etiology ; Postoperative Complications ; epidemiology ; etiology ; Rehydration Solutions ; administration & dosage ; adverse effects

PURPOSE: Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presented data showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. The purpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 compared to cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337 represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporine A was determined using an experimental murine dry eye model. METHODS: The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6 mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A or HL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topically administered twice per day to dry eye induced murine corneas for 1 week. RESULTS: The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced corneal erosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topically applied cyclosporine A and HL036337 at 1 mg/mL. CONCLUSIONS: HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.
Animals ; Cornea/diagnostic imaging ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Dry Eye Syndromes/diagnosis/*drug therapy ; Female ; Mice ; Mice, Inbred C57BL ; Microscopy, Acoustic ; Ophthalmic Solutions/administration & dosage ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

PURPOSE: To identify the risk factors associated with fluoroquinolone resistance in patients undergoing cataract surgery. METHODS: A total of 1,125 patients (1,125 eyes) who underwent cataract surgery at Veterans Health Service Medical Center from May 2011 to July 2012 were enrolled in this study. Conjunctival cultures were obtained from the patients on the day of surgery before instillation of any ophthalmic solutions. The medical records of patients with positive coagulase negative staphylococcus (CNS) and Staphylococcus aureus (S. aureus) cultures were reviewed to determine factors associated with fluoroquinolone resistance. RESULTS: Of 734 CNS and S. aureus cultures, 175 (23.8%) were resistant to ciprofloxacin, levofloxacin, gatifloxacin, or moxifloxacin. Use of fluoroquinolone within 3 months and within 1 year before surgery, topical antibiotic use other than fluoroquinolone, systemic antibiotic use, recent hospitalization, ocular surgery, intravitreal injection and use of eyedrops containing benzalkonium chloride were significantly more frequent in resistant isolates than in susceptible isolates. In multivariable logistic regression analysis, ocular surgery (odds ratio [OR], 8.457), recent hospitalization (OR, 6.646) and use of fluoroquinolone within 3 months before surgery (OR, 4.918) were significant predictors of fluoroquinolone resistance, along with intravitreal injection (OR, 2.976), systemic antibiotic use (OR, 2.665), use of eyedrops containing benzalkonium chloride (OR, 2.323), use of fluoroquinolone within 1 year before surgery (OR, 1.943) and topical antibiotic use other than fluoroquinolone (OR, 1.673). CONCLUSIONS: Recent topical fluoroquinolone use, hospitalization and ocular surgery were significantly associated with fluoroquinolone resistance in CNS and S. aureus isolates from ocular culture.
Aged ; Anti-Bacterial Agents/*administration & dosage ; *Drug Resistance, Bacterial ; Eye Infections, Bacterial/drug therapy/*microbiology ; Female ; Fluoroquinolones/*administration & dosage ; Humans ; Male ; Ophthalmic Solutions ; Retrospective Studies ; Risk Factors ; Staphylococcal Infections/drug therapy/*microbiology ; Staphylococcus aureus/drug effects/*isolation & purification

PURPOSE: To compare the recurrence rates and complications associated with instillation of topical mitomycin C, cyclosporine, and bevacizumab after primary pterygium surgery. METHODS: Between July 2013 and June 2014, we performed surgery using the bare sclera method on 132 eyes (132 patients) with primary pterygium. We randomly selected 33 eyes (33 patients) and treated them with artificial tears four times a day for three months, 29 eyes (29 patients) were treated with topical 0.02% mitomycin C four times a day for five days, 34 eyes (34 patients) were treated with topical 0.05% cyclosporine four times a day for three months, and 36 eyes (36 patients) were treated with topical 2.5% bevacizumab four times a day for three months after surgery. We prospectively determined the recurrence rates of pterygium and complications at the six-month follow-up examination. RESULTS: At six months after surgery, the recurrence rates in each group were as follows: 45.5% (15 eyes) in the control group, 10.3% (three eyes) in the mitomycin C group, 20.6% (seven eyes) in the cyclosporine group, and 41.7% (15 eyes) in the bevacizumab group (p = 0.004). No serious complications, except subconjunctival hemorrhages, were observed in any group. CONCLUSIONS: Groups receiving topical 0.02% mitomycin C and 0.05% cyclosporine after surgery showed lower recurrence rates than the control group; however, no difference in recurrence rate was observed between the control group and the group receiving topical 2.5% bevacizumab after surgery.
Administration, Topical ; Aged ; Aged, 80 and over ; Alkylating Agents/administration & dosage ; Angiogenesis Inhibitors/administration & dosage ; Bevacizumab/*administration & dosage ; Cell Count ; Combined Modality Therapy ; Cyclosporine/*administration & dosage ; Double-Blind Method ; Endothelium, Corneal/pathology ; Female ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Middle Aged ; Mitomycin/*administration & dosage ; Ophthalmic Solutions ; Ophthalmologic Surgical Procedures ; Prospective Studies ; Pterygium/diagnosis/*drug therapy/*surgery ; Recurrence ; Vascular Endothelial Growth Factor A/antagonists & inhibitors

PURPOSE: To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE). METHODS: Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining. RESULTS: There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group. CONCLUSIONS: The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.
Animals ; Conjunctiva/*drug effects/pathology ; Cornea/metabolism ; Disease Models, Animal ; Drug Combinations ; Dry Eye Syndromes/*drug therapy/metabolism ; Emollients/administration & dosage ; Female ; Goblet Cells/drug effects/metabolism/pathology ; Hyaluronic Acid/*administration & dosage ; Mice ; Mice, Inbred C57BL ; Mineral Oil/*administration & dosage ; Ophthalmic Solutions ; Tears/*metabolism ; Viscosupplements/administration & dosage

PURPOSE: To evaluate and compare the toxic effects of eyedrops containing a fixed combination of 2.0% dorzolamide and 0.5% maleate timolol with or without preservatives on rabbit corneal endothelium. METHODS: This study was performed with 22 eyes of New Zealand white rabbits. Dorzolamide/timolol eyedrops with preservative (Cosopt group) or without preservative (Cosopt-S group) were diluted with a balanced salt solution at a 1 : 1 ratio. We injected 0.1 mL of diluted Cosopt into the anterior chamber of left eyes and an equal volume of diluted Cosopt-S into the anterior chamber of right eyes. Corneal thickness, corneal haze, and conjunctival injection were measured before and 24 hours after treatment. Endothelial damage was compared between both eyes by vital staining (alizarin red/trypan blue staining), live/dead cell assay, TUNEL assay, and scanning electron microscopy. RESULTS: Corneal endothelial damage was severe in the Cosopt group. Cosopt-treated eyes exhibited remarkable corneal edema and prominent apoptosis of endothelial cells. In addition, the live/dead cell assay revealed many dead cells in the endothelium, and scanning electron microscopy analysis showed that corneal endothelial cells exhibited a partial loss of microvilli on the surface as well as extensive destruction of intercellular junctions. However, in the Cosopt-S group, corneal edema was mild and the damage to the corneal endothelium was minimal. CONCLUSIONS: The main cause of corneal endothelial toxicity was due to the preservative in the dorzolamide/timolol fixed combination eyedrops, and not the active ingredient. Thus, it appears to be safer to use preservative-free eyedrops during the early postoperative period.
Animals ; Anterior Chamber/drug effects ; Apoptosis ; Corneal Edema/chemically induced/*pathology ; Disease Models, Animal ; Drug Combinations ; Endothelium, Corneal/drug effects/*pathology ; In Situ Nick-End Labeling ; Ophthalmic Solutions ; Rabbits ; Sulfonamides/administration & dosage/*toxicity ; Thiophenes/administration & dosage/*toxicity ; Timolol/administration & dosage/*toxicity

OBJECTIVETo dicuss the clinical efficacy of Timolol Maleate Eye Drops in the treatment of superficial infantile hemangiomas. Methods From April 2012 to May 2014, 210 patients with superficial infantile hemangiomas were included. According to the parents' choice, a total of 176 cases were treated with Timolol Maleate Eye Drops as the treatment group, and the 34 cases who received the treatment of "wait and see" was included in the control group. In the treatment group, the gauzes were dipped into the eye drops and putted evenly on the surface of the hemangioma, 3-4 times daily and lasted for more than 20 minutes. The gauze should completely cover the surface of the tumor. The follow-up periods were 3 weeks and 6 months after treatment with the pictures to record the treatment effect. The therapeutic effect was graded as: grade I (unable to control the growth of the hemangioma), II (the growth of the hemangioma stagnated), III (hemangioma significantly subsided), IV (the hemangioma completely disappeared). The effective rate included the cases with grade II and above grade II . The cure cases included the cases with grade IV. The data was analyzed with the statistical software SPSS 17.0 and the Chi-square test (P < 0.05).

RESULTS3 cases in the treatment group showed eczema action. Tumor ulcer happened in 1 case in treatment group. The side effect rate was 2.3% . The results at 3 weeks following in the treatment group showed that the growth of the hemangioma were stagnated in 154 cases. The color of hemangioma became darker in different degrees than before, and the texture of the hemangioma became soft in majority of children, and the thickness of hemangioma became thinner in some cases. However, only 4 cases showed the hemangiomas were subsided, 18 cases showed the color of the part of the hemangiomas were brighter than before, and 12 cases of the hemangiomas remained original state in the control group. The results of 6 weeks following the treatment showed that 18 patients in the treatment group reached the standard of the grade IV, 84 patients reached the standard of the grade III, 60 patients achieved in the standard of grade II, and only 14 patients showed the volume of hemangiomas were increased as grade I. The effective rate was 58. 0% , and the cure rate was 10. 2% in treatment group. In control group, no children reached the standard of the grade IV, 4 cases reached the standard of grade III, 13 cases who remained original state reached the standard of grade II, and 17 cases showed the volume of hemangiomas continued to increase as grade I . The effective rate was 11. 8% , and the cure rate was 0. By comparison, the effective rate and the cure rate in the control group were relatively lower than those in the treatment group (P < 0.05).

CONCLUSIONSThe efficacy of Timolol Maleate Eye Drops in the treatment of superficial infantile hemangioma is exact, especially in the proliferative phase of the infantile hemangioma. It is safe and easy to perform with mild side effect. It should be selected as first-line treatment.

Administration, Topical ; Adrenergic beta-Antagonists ; administration & dosage ; Child ; Hemangioma ; drug therapy ; Humans ; Ophthalmic Solutions ; administration & dosage ; Skin Neoplasms ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; Treatment Outcome ; Watchful Waiting