Effect of sofosbuvir and daclatasvir on lipid profile, glycemic control and quality of life index in chronic hepatitis C, genotype 3 patients.

OBJECTIVES: The management of hepatitis C has progressed from interferon-based therapy to oral direct acting antiviral therapy. Deranged lipid levels (total cholesterol, triglyceride) after treatment with interferon-based therapy are well known. There is a paucity of data on changes in lipid profile, glycemic parameters and alteration in quality of life with the newer regimen. This study was designed to assess the changes in lipid profile, glycemic parameters, quality of life in chronic hepatitis C patients with genotype 3 after treatment with sofosbuvir and daclatasvir. METHODS: The study was a single-centre, prospective study, conducted at tertiary care hospital from January 2017 to December 2017. Fifty patients, who received sofosbuvir (400 mg) and daclatasvir (60 mg) orally once daily for a period of 12 weeks for chronic hepatitis C and genotype 3, were recruited. RESULTS: Total cholesterol levels (166.9 ± 23.8 to 192.4 ± 34.5 mg/dL, p-value < 0.0001) and low-density cholesterol (LDL) levels (100.9 ± 22.8 to 121.6 ± 37.2, p-value < 0.0001) were elevated after the treatment. A significant decrease in median levels of glycated hemoglobin (HbA1c) was observed (5.57% to 5.41%, p-value < 0.002). Quality of life markedly improved in all domains, i.e. physical, physiological, environmental, and social relationships according to an abbreviated form of World Health Organization quality of life assessment named WHOQOL-BREF questionnaire. Treatment was found to be effective with sustained virological response (SVR) achieved in 94% patients. CONCLUSIONS: Our study reports a substantial increment in total cholesterol, and low-density lipoprotein with sofosbuvir and daclatasvir treatment though it achieved SVR in 94% of patients and improved their quality of life.

AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against ischemic memory improving cutaneous wound healing.

Peripheral vasculopathies cause severe wound hypoxia inducing the hypoxamiR miR-210. High level of miR-210, persisting in wound-edge tissue as ischemic memory, suppresses oxidative metabolism and inhibits cell proliferation necessary for healing. In wound-edge tissue of chronic wound patients, elevated miR-210 was tightly associated with inhibition of epidermal cell proliferation as evident by lowered Ki67 immunoreactivity. To inhibit miR-210 in murine ischemic wound-edge tissue, we report the formulation of antihypoxamiR functionalized gramicidin lipid nanoparticles (AFGLN). A single intradermal delivery of AFGLN encapsulating LNA-conjugated anti-hypoximiR-210 (AFGLNmiR-210) lowered miR-210 level in the ischemic wound-edge tissue. In repTOP™mitoIRE mice, AFGLNmiR-210 rescued keratinocyte proliferation as visualized by in vivo imaging system (IVIS). 31P NMR studies showed elevated ATP content at the ischemic wound-edge tissue following AFGLNmiR-210 treatment indicating recovering bioenergetics necessary for healing. Consistently, AFGLNmiR-210 improved ischemic wound closure. The nanoparticle based approach reported herein is effective for miR-directed wound therapeutics warranting further translational development.

Connectivity of the intracytoplasmic membrane of Rhodobacter sphaeroides: a functional approach.

The photosynthetic apparatus in the bacterium Rhodobacter sphaeroides is mostly present in intracytoplasmic membrane invaginations. It has long been debated whether these invaginations remain in topological continuity with the cytoplasmic membrane, or form isolated chromatophore vesicles. This issue is revisited here by functional approaches. The ionophore gramicidin was used as a probe of the relative size of the electro-osmotic units in isolated chromatophores, spheroplasts, or intact cells. The decay of the membrane potential was monitored from the electrochromic shift of carotenoids. The half-time of the decay induced by a single channel in intact cells was about 6 ms, thus three orders of magnitude slower than in isolated chromatophores. In spheroplasts obtained by lysis of the cell wall, the single channel decay was still slower (~23 ms) and the sensitivity toward the gramicidin concentration was enhanced 1,000-fold with respect to isolated chromatophores. These results indicate that the area of the functional membrane in cells or spheroplasts is about three orders of magnitude larger than that of isolated chromatophores. Intracytoplasmic vesicles, if present, could contribute to at most 10% of the photosynthetic apparatus in intact cells of Rba. sphaeroides. Similar conclusions were obtained from the effect of a ∆pH-induced diffusion potential in intact cells. This caused a large electrochromic response of carotenoids, of similar amplitude as the light-induced change, indicating that most of the system is sensitive to a pH change of the external medium. A single internal membrane and periplasmic space may offer significant advantages concerning renewal of the photosynthetic apparatus and reallocation of the components shared with other bioenergetic pathways.

Estilos de vida nas capitais brasileiras segundo a Pesquisa Nacional de Saúde e o Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas Não Transmissíveis por Inquérito Telefônico (Vigitel), 2013 / Lifestyles in Brazilian capitals according to the National Health Survey and the Surveillance System for Protective and Risk Factors for Chronic Diseases by Telephone Survey (Vigitel), 2013

RESUMO: Objetivo: Descrever os principais resultados dos fatores de risco e proteção de doenças crônicas não transmissíveis (DCNT), nas capitais brasileiras e no Distrito Federal, coletados pela Pesquisa Nacional de Saúde (PNS) e pelo Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas Não Transmissíveis por Inquérito Telefônico (Vigitel) no ano de 2013. Métodos Análise de dados advindos da PNS e do Vigitel, pesquisas realizadas no ano de 2013. Foram analisados indicadores sobre tabagismo, consumo de álcool, alimentação e atividade física, segundo sexo, com intervalo de confiança de 95% (IC95%). Resultados: As prevalências encontradas foram: fumantes atuais de cigarro - PNS 12,5% e Vigitel 11,3%; consumo abusivo de bebida alcoólica - PNS 14,9% e Vigitel 16,4%; consumo recomendado de frutas e hortaliças - PNS 41,8% e Vigitel 23,6%; prática de atividade física no tempo livre - PNS 26,6% e Vigitel 33,8%. Conclusão: Os resultados dos indicadores foram semelhantes, em especial quando as perguntas e opções de resposta também eram. As pesquisas são úteis para o monitoramento dos fatores de risco e proteção das DCNT, podendo apoiar programas de promoção da saúde.

ABSTRACT: Objective: To describe risk and protective factors for chronic diseases, in Brazilian capitals and the Federal District, collected by the National Health Survey (PNS) and by the Surveillance System for Protective and Risk Factors for Chronic Diseases by Telephone Survey (Vigitel) in 2013. Methods: Data analysis of the studies conducted by the PNS and Vigitel in 2013 was performed. Indicators analyzed were: smoking, alcohol consumption, diet, and physical activity, according to sex, with a 95% confidence interval. Results: The prevalences found were: current cigarette smokers: PNS, 12.5% and Vigitel, 11.3%; abuse of alcoholic beverages: PNS, 14.9% and Vigitel, 16.4%; recommended intake of fruits and vegetables: PNS, 41.8% and Vigitel, 23.6%; and physical activity in leisure time: PNS, 26.6% and Vigitel, 35.8%. Conclusion: In the majority of indicators, the results were similar, especially when the questions and response options were equal. Surveys are useful for the monitoring of risk and protective factors of noncommunicable diseases and can support health promotion programs.

Polymersomes with engineered ion selective permeability as stimuli-responsive nanocompartments with preserved architecture.

Following a biomimetic approach, we present here polymer vesicles (polymersomes) with ion selective permeability, achieved by inserting gramicidin (gA) biopores in their membrane. Encapsulation of pH-, Na(+)- and K(+)- sensitive dyes inside the polymersome cavity was used to assess the proper insertion and functionality of gA inside the synthetic membrane. A combination of light scattering, transmission electron microscopy, and fluorescence correlation spectroscopy was used to show that neither the size, nor the morphology of the polymersomes was affected by successful insertion of gA in the polymer membrane. Interestingly, proper insertion and functionality of gA were demonstrated for membranes with thicknesses in the range 9.2-12.1 nm, which are significantly greater than membrane lipid counterparts. Both polymersomes with sizes around 100 nm and giant unilamellar vesicles (GUVs) with inserted gA exhibited efficient time response to pH- and ions and therefore are ideal candidates for designing nanoreactors or biosensors for a variety of applications in which changes in the environment, such as variations of ionic concentration or pH, are required.

Functional and structural insights on self-assembled nanofiber-based novel antibacterial ointment from antimicrobial peptides, bacitracin and gramicidin S.

A novel antibacterial ointment using bacitracin, specific for Gram-positive bacteria, and gramicidin S, a highly toxic antibacterial peptide, was here developed showing broad-spectrum antibacterial activities against pathogenic strains with less toxicity after self-assembly into nanofiber structures. Such structures were confirmed with scanning electron microscopy and CD analyses. In addition, in silico studies using docking associated with molecular dynamics were carried out to obtain information about fiber structural oligomerization. Thus, the bacitracin and gramicidin S-based self-assembled nanopeptide ribbon may be a successful ointment formulation for bacterial infection control.

Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma.

Lactosylated gramicidin-containing lipid nanoparticles (Lac-GLN) were developed for delivery of anti-microRNA-155 (anti-miR-155) to hepatocellular carcinoma (HCC) cells. MiR-155 is an oncomiR frequently elevated in HCC. The Lac-GLN formulation contained N-lactobionyl-dioleoyl phosphatidylethanolamine (Lac-DOPE), a ligand for the asialoglycoprotein receptor (ASGR), and an antibiotic peptide gramicidin A. The nanoparticles exhibited a mean particle diameter of 73 nm, zeta potential of +3.5mV, anti-miR encapsulation efficiency of 88%, and excellent colloidal stability at 4°C. Lac-GLN effectively delivered anti-miR-155 to HCC cells with a 16.1- and 4.1-fold up-regulation of miR-155 targets C/EBPß and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000. In mice, intravenous injection of Lac-GLN containing Cy3-anti-miR-155 led to preferential accumulation of the anti-miR-155 in hepatocytes. Intravenous administration of 1.5 mg/kg anti-miR-155 loaded Lac-GLN resulted in up-regulation of C/EBPß and FOXP3 by 6.9- and 2.2-fold, respectively. These results suggest potential application of Lac-GLN as a liver-specific delivery vehicle for anti-miR therapy.

The association between exit site infection and subsequent peritonitis among peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES: Peritonitis is the most common infectious complication seen in peritoneal dialysis (PD). Traditionally, exit site infection (ESI) has been thought to predispose PD patients to peritonitis, although the risks have not been quantified. This study aimed to quantify the risk of PD peritonitis after ESI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from 203 clinically stable PD patients >18 years of age who were followed as part of a randomized controlled trial over 18 months were used to estimate the risk of developing peritonitis within 30 days of an ESI compared with individuals who did not have a recent ESI. Sensitivity analyses were performed at 15, 45, and 60 days. RESULTS: Patients were mostly male (64.5%) and Caucasian, with a mean age of 60.5 ± 14.4 years. There were 44 ESIs and 87 peritonitis episodes during the 18-month study. Seven patients had an ESI followed by peritonitis within 30 days. Using a frailty model, patients who had an ESI had a significantly higher risk of developing peritonitis within 30 days, even if the ESI was appropriately treated. This risk was maximal early on and diminished with time, with hazard ratios (95% confidence interval) of 11.1 at 15 days (HR=11.1, 95% CI=4.9-25.1), 5.3 at 45 days (2.5-11.3), and 4.9 at 60 days (2.4-9.9). In 2.3% of patients, subsequent peritonitis was caused by the same organism as the previous ESI. CONCLUSIONS: A strong association between a treated ESI and subsequent PD peritonitis was present up to 60 days after initial diagnosis.

A randomized controlled trial comparing mupirocin and polysporin triple ointments in peritoneal dialysis patients: the MP3 Study.

BACKGROUND AND OBJECTIVES: Infectious complications remain a significant cause of peritoneal dialysis (PD) technique failure. Topical ointments seem to reduce peritonitis; however, concerns over resistance have led to a quest for alternative agents. This study examined the effectiveness of applying topical Polysporin Triple ointment (P(3)) against mupirocin in a multi-centered, double-blind, randomized controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: PD patients routinely applied either P(3) or mupirocin ointment to their exit site. Patients were followed for 18 months or until death or catheter removal. The primary study outcome was a composite endpoint of exit-site infection (ESI), tunnel infection, or peritonitis. RESULTS: Seventy-five of 201 randomized patients experienced a primary outcome event (51 peritonitis episodes, 24 ESIs). No difference was seen in the time to first event for P(3) (13.2 months; 95% confidence interval, 11.9-14.5) and mupirocin (14.0 months; 95% confidence interval, 12.7-15.4) (P=0.41). Twice as many patients reported redness at the exit site in the P(3) group (14 versus 6, P=0.10). Over the complete study period, a higher rate per year of fungal ESIs was seen in patients using P(3) (0.07 versus 0.01; P=0.02) with a corresponding increase in fungal peritonitis (0.04 versus 0.00, respectively; P<0.05). CONCLUSIONS: This study shows that P(3) is not superior to mupirocin in the prophylaxis of PD-related infections. Colonization of the exit site with fungal organisms is of concern and warrants further study. As such, the use of P(3) over mupirocin is not advocated in the prophylaxis of PD-related infections.

Structural transition in micelles: novel insight into microenvironmental changes in polarity and dynamics.

Structural transitions involving shape changes play an important role in cellular physiology. Such transition can be conveniently induced in charged micelles by increasing ionic strength of the medium. Shape changes have recently been shown to result in altered packing and lowering of micellar polarity. As a consequence of reduced polarity, the ionization states of micelle-bound molecules vary in micelles of different shape. The changes in micellar organization and dynamics due to structural transition can be effectively monitored utilizing the red edge excitation shift (REES). These changes are influenced by the position (location) of the probe in the micelle, i.e., the region of the micelle being monitored. Changes in organization and dynamics of probes and peptides upon structural transition are discussed with representative examples. We envisage that the reduction in micellar polarity and tighter packing upon structural transition represent important factors in the incorporation of drugs in micelles (nano-carriers), since micellar polarity plays a crucial role in the incorporation of drugs.

Exogenous Cushing's syndrome due to topical corticosteroid application: case report and review literature.

Prolonged use of topical corticosteroids causes systemic adverse effects including Cushing's syndrome and hypothalamic-pituitary-adrenal (HPA) axis suppression, which is less common than that of the oral or parenteral route. At least 43 cases with iatrogenic Cushing syndrome from very potent topical steroid usage (Clobetasol) in children and adult have been published over the last 35 years particularly in developing countries. In children group (n = 22), most are infants with diaper dermatitis and two cases who had started topical application at a very early age and died from severe disseminated CMV infection. For the adult group (n = 21), the most common purpose of steroid use was for treatment of Psoriasis. The recovery period of HPA axis suppression was 3.49 ± 2.92 and 3.84 ± 2.51 months in children and adult, respectively. We report on an 8-month-old female infant who developed Cushing's syndrome and adrenal insufficiency after diaper dermatitis treatment through the misuse of Clobetasol without doctor's prescription. Physiologic dose of hydrocortisone was prescribed to prevent an adrenal crisis for 3 months and discontinued when HPA axis recovery was confirmed by normal morning cortisol and ACTH levels.

Optimization of antimicrobial drug gramicidin S dosing regime using biosimulations.

In this paper we have developed a model of antimicrobial effect of gramicidin S. This model has allowed us to predict the dependence of antimicrobial effect of the drug applied as oral melting tablets on dosage, time of resorption and minimal inhibitory concentration (MIC) of the drug characterizing its ability to kill different bacteria. The model has been employed to optimize dosing regime of gramicidin S containing drug Grammidin. Efficacy of the drug has been studied for the diverse gram-positive and gram-negative bacteria with different MIC. The number of bacteria located in the oral cavity and killed by one-pass administration of the drug (resolution of one tablet) has been calculated under condition of various dosing regimes. Based on the simulation results it has been found that (1) twofold prolongation of prescribed resorption time (from 30 to 60min) of the tablet comprising standard dosage of 3mg of gramicidin S results in 1.5-fold increase in efficacy, (2) 1.5-fold decrease in gramicidin S dosage (from 3 to 2mg per administration) under condition of holding prescribed resorption time (30min) does not lead to any considerable decrease in the efficacy of the drug.

Topical ciprofloxin versus topical framycetin-gramicidin-dexamethasone in Australian aboriginal children with recently treated chronic suppurative otitis media: a randomized controlled trial.

BACKGROUND: Chronic suppurative otitis media (CSOM) affects many children in disadvantaged populations. The most appropriate topical antibiotic treatment in children with persistent disease is unclear. METHODS: Children with CSOM despite standard topical treatment were randomized to 6-8 weeks of topical ciprofloxacin (CIP) versus topical framycetin-gramicidin-dexamethasone (FGD). Otoscopic, audiologic, and microbiologic outcomes were measured using standardized assessments and blinding. RESULTS: Ninety-seven children were randomized. Ear discharge failed to resolve at the end of therapy in 70% children regardless of allocation [risk difference = -2%; (95% CI: -20 to 16)]. Healing of the tympanic membrane occurred in one of 50 children in the CIP group and none of 47 children in the FGD group. Severity of discharge failed to improve in more than 50% children in each group, and mean hearing threshold (38 dB and 35 dB) and proportion of children with greater than 25 dB hearing loss (98% and 88%) were not significantly different between the CIP and FGD groups. Side effects were rare. CONCLUSIONS: This study showed a similarly low rate of improvement or cure in children with persistent CSOM for both CIP and FGD topical therapies. Complications and side effects were insufficient to cease therapy or inform prescribing of either therapy.

Expansile properties of otowicks: an in vitro study.

OBJECTIVE: To determine the expansile and absorptive properties of the expandable ear wick when tested with commonly prescribed ear drop preparations. DESIGN: This in vitro study assessed wick expansion and absorption of drops when different ear drop preparations were applied. Nine commonly used ear drop preparations were tested (Gentisone HC, Sofradex, Otomize, Betnesol, Exocin, Canesten, Locorten-Vioform, EarCalm and ichthammol glycerin) with a standard expandable ear wick. MAIN OUTCOME MEASURES: Weight, length and width of otowick following exposure to ear drops. RESULTS: There was a marked difference in the absorption and expansion of the otowick when different drops were used. This corresponded to the aqueous or oil base of each preparation. All aqueous ear drop preparations (i.e. Gentisone HC, Sofradex, Otomize, Betnesol, Exocin and EarCalm) produced similar rates of absorption into, and expansion of, the otowick. The oil-based ear drop preparations (i.e. Canesten, Locorten-Vioform and ichthammol glycerin) failed to expand the wick and showed poor rates of absorption into the wick. CONCLUSION: Expandable ear wicks should only be used in conjunction with aqueous ear drops. When using expandable otowicks as an adjunct to treating fungal otitis externa, acetic acid ear drops should be prescribed, as all other anti-fungal drops are oil-based.

A randomised controlled trial comparing Triadcortyl with 10% glycerine-ichthammol in the initial treatment of severe acute otitis externa.

Acute otitis externa is a common clinical condition accounting for a large proportion of patients attending the otolaryngology department, although milder cases are often managed in primary care. Treatment of the most severe forms of otitis externa involves aural toilet, followed by the application of a topical preparation, commonly in the form of an ear canal dressing. A prospective single-blind randomized controlled trial was performed to compare the efficacy of 10% glycerine-ichthammol (GI) solution and Triadcortyl (TAC) ointment, both applied as ear canal dressings, in the initial management of severe acute otitis externa. A total of 64 patients were studied. Both treatment modalities were proven efficacious in the treatment of severe acute otitis externa. Although there was a statistically significant improvement of pain parameters in the TAC group, we found no significant differences in clinical findings between the two groups. Therefore, it is recommended that GI dressing can be used instead of an antibiotic dressing as an initial treatment of severe acute otitis externa on the basis of cost, avoidance of resistance and toxicity.

Effectiveness of combined antibiotic ophthalmic solution in the treatment of hordeolum after incision and curettage: a randomized, placebo-controlled trial: a pilot study.

The presented pilot study compared the effectiveness of combined antibiotic ophthalmic solution (neomycin sulfate, polymyxin B sulfate and gramicidin) with a placebo (artificial tear) in the treatment of hordeolum after incision and curettage (I&C). A randomized, placebo-controlled trial with patients and investigators blinded from the start started from June 2002 to May 2003. Subjects were patients with untreated hordeolum who subsequently underwent I&C at the Ophthalmology Department. The patients were randomized into 2 groups: group A for combined antibiotic ophthalmic solution, and group B for artificial tear containing the antibiotic solution base. Pain score, mass size and duration of cure were recorded before and on the 3rd and 7th day after treatment. The study included 14 patients in each group. Two subjects in group A and three subjects in group B dropped out. There were no statistically significant differences of all outcomes in both groups, even with the intention-to-treat analysis. The conclusion is combined antibiotic ophthalmic solution is not more effective than placebo in the treatment of hordeolum after I&C.

A blinded in-vitro study to compare the efficacy of five topical ear drops in clearing grommets blocked with thick middle ear effusion fluid.

OBJECTIVE: To compare the efficacy of 5% NaHCO3, 3% H2O2, Sofradex (dexamethasone sodium metasulphobenzoate 0.05%, framycetin sulphate 0.5%, gramicidin 0.005%), 0.33% acetic acid and 0.9% NaCl eardrops in clearing grommets blocked with harvested thick middle ear effusion fluid. STUDY DESIGN: A blinded in-vitro study. SETTING: District general hospital. PARTICIPANTS: A total of 473 grommets were blocked with freshly harvested unpooled thick middle ear effusion fluid obtained from 68 patients. MAIN OUTCOME MEASURES: Patency of the grommets before and 7 days after intervention was ascertained by tympanometry and close visual inspection. RESULTS: Instillation of eardrops leads to a statistically significant increase in the clearance of grommets as compared with not using any drops (chi2 = 14.3, d.f. = 5, P = 0.006). The numbers needed to treat were 2.8 for NaHCO3, 3.2 for 0.9% NaCl, 3.9 for 0.33% acetic Acid, 4.4 for Sofradex and 9.5 for H2O2 eardrops. Pair-wise comparison was only significant for comparison between 5% NaHCO3 and 3% H2O2 eardrops (Bonferroni corrected P = 0.01, odds ratio = 4.3, CI = 1.9-9.9). CONCLUSIONS: Use of eardrops leads to a clinically and statistically significant increase in the clearance of blocked grommets. Of the five drops used, 5% NaHCO3 was the most efficacious and 3% H2O2 the least efficacious. Limitations of this in-vitro study are recognized and a prospective in-vivo double blind randomized controlled trial is planned.

The use of perioperative Sofradex eardrops in preventing tympanostomy tube blockage: a prospective double-blinded randomized-controlled trial.

Around 11-12% of tympanostomy tubes are reported to become blocked by middle ear secretions or blood immediately following surgery, and so no longer function. Many otologists routinely instil an antibiotic and steroid-containing solution at the time of surgery in the belief that this may reduce this complication. The aim of the study was to investigate the efficacy of instilling the antibiotic and steroid-containing solution Sofradex at the time of grommet insertion in preventing grommet blockage. Double-blind randomized-controlled trial, comparing rates of grommet blockage in ears treated with Sofradex drops against control (no drops) in patients undergoing bilateral grommet insertion. Sixty-one pairs of results were obtained. There was a significant difference between the rates of grommet blockage in the two groups. Grommets with Sofradex drops instilled perioperatively were nine times less likely to be blocked than controls [1.6%versus 13.1%, odds ratio (Sofradex/control) = 9.06, 95% confidence interval (CI): 1.04-78.82, P = 0.05]. There was no association between grommet blockage and perioperative bleeding or the nature and presence of middle ear secretions. Sofradex eardrops are effective in reducing the rate of grommet blockage when instilled perioperatively.

Comparison of topical tobramycin-dexamethasone with dexamethasone-neomycin-polymyxin and neomycin-polymyxin-gramicidin for control of inflammation after cataract surgery: results of a multicenter, prospective, three-arm, randomized, double-masked, controlled, parallel-group study.

BACKGROUND: Intraocular inflammation is typically treated with a combination of anti-inflammatory and anti-infective drugs. Tobramycin-dexamethasone (TD) has not been associated with any serious adverse events, indicating good tolerability. OBJECTIVE: The aims of this study were the following: (1) to demonstrate noninferiority of TD compared with dexamethasone-neomycin-polymyxin (DNP) in terms of anti-inflammatory efficacy, (2) to compare the anti-inflammatory efficacy of TD and DNP with that of a "placebo" control (antibiotic without anti-inflammatory agent), and (3) to provide additional safety data on TD. METHODS: This prospective, double-masked, parallel-group study was conducted at 22 ophthalmology clinics across Europe and Brazil. Patients aged > 18 years undergoing cataract surgery were randomly assigned, in a 2:2:1 ratio, to receive tobramycin 3 mg/mL plus dexamethasone 1 mg/mL, dexamethasone 1 mg/mL plus neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 6000 IU/mL, or neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 7500 IU/mL plus gramicidin 20 microg/mL. All treatments were given as 1 drop instilled in the operated eye q.i.d. for 21 days. The primary efficacy end point, intraocular inflammation (determined using the sum of scores on anterior chamber cells and aqueous flare), was assessed at days 3, 8, 14, and 21 after surgery. RESULTS: A total of 271 patients were enrolled (158 women, 113 men; age range 42-90 years) (TD, 104 patients; DNP, 110 patients; and neomycin-polymyxin-gramicidin [NPG], 57 patients). Intraocular inflammation was similar in the TD and DNP groups at all time points. At days 8, 14, and 21, inflammation scores were significantly lower with TD than with NPG (all, P < 0.05). At day 8, the inflammation score was significantly lower with DNP than with NPG (P < 0.05). A greater number of patients receiving NPG experienced treatment-related ocular allergic reactions compared with patients receiving TD (P < 0.05). One patient receiving TD (1.0%) and 5 given NPG (9.0%) were withdrawn due to ocular allergic reactions. None of the patients experienced an increase in intraocular pressure > or =10 mm Hg from baseline. CONCLUSIONS: In this study of patients undergoing cataract surgery combination therapy with TD was noninferior to DNP and was well tolerated.