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.

A general practice study to compare the efficacy and tolerability of a spray ('Otomize') versus a standard drop formulation ('Sofradex') in the treatment of patients with otitis externa.

In an open, multi-centre study in general practice, a comparison was made of the efficacy, tolerability and acceptability of a neomycin/dexamethasone preparation administered by metered-dose spray ('Otomize') and a framycetin/gramicidin/dexamethasone preparation ('Sofradex') administered as drops in 60 patients with otitis externa. Patients were allocated at random to receive one or other preparations 3-times daily for 10 days and were followed-up again 14 days after cessation of therapy. Clinical assessments were carried out under observer blind conditions on entry (Day 0) and on Days 10 and 24 of the severity of erythema, swelling and debris in the affected ear(s). A global assessment of clinical outcome was made by the doctor on Day 10. There were no significant differences in the two groups at the start of treatment. Significant improvement occurred in both groups from Day 0 to Day 10 and from Day 10 to Day 24 in all symptoms, with the proportion symptom-free in the 'Otomize' group significantly greater than in the 'Sofradex' group at 24 days, and approaching significance at 10 days. Significantly more patients in the 'Otomize' group were rated as having a good clinical outcome by the physician, and fewer patients experienced discomfort on application. Few side-effects were reported by either treatment group, none necessitating discontinuation of therapy.

Comparative efficacy and tolerability of two ointment and suppository preparations ('Uniroid' and 'Proctosedyl') in the treatment of second degree haemorrhoids in general practice.

A multi-centre general practice, open study was carried out in 89 patients with second degree haemorrhoids to compare the efficacy and tolerability of two antibiotic-corticosteroid combinations ('Uniroid' and 'Proctosedyl') in ointment and suppository formulations. Patients were allocated at random into 4 groups and received treatment with one of the trial preparations for 1, 2 or 3 weeks, as required, with weekly assessments of response. There were no significant differences between the various groups at the start of treatment. Significant improvement occurred in all groups during treatment. Both suppository and ointment formulations were broadly comparable and control of symptoms was achieved from Week 2 onwards, building up to levels in excess of 90% after 3 weeks of therapy. With regard to the symptoms of pain and itching, suppositories gave marginally greater relief in the early stages of treatment, while both ointment and suppositories were associated with similar reduction in bleeding from haemorrhoids. Whereas both suppository formulations were about equal in reducing anal discharge, 'Uniroid' ointment was clinically superior to 'Proctosedyl' ointment in controlling this symptom over the 3-week trial period. No unwanted effects were experienced attributable to treatment. No statistically significant differences between the two ointment and the two suppository formulations were identified in this study and all four preparations were found to be efficacious in the majority of patients studied.

Contact allergy to various components of topical preparations for treatment of external otitis.

Patients suffering from chronic external otitis had developed contact allergies to one or more compounds of topical preparations in 40% of 142 tested patients. Neomycin and framycetin caused most of the allergic reactions (16.2%) followed by chinoform (7.0%), chloramphenicol and polymyxin (4.2%). Preservatives of the topical otic preparations such as benzethonium chloride (8.5%), benzalkonium chloride (6.3%) and thimerosal (merthiolate) (5.6%) were also common causes of allergic reactions. An epicutaneous test (patch test) using compounds in topical preparations should be done in cases of prolonged, treatment resistant external otitis.

[Drug ototoxicity. Medicolegal aspects]. / L'ototoxicité médicamenteuse. Aspects médico-légaux.

Drug ototoxicity is a preoccupying iatrogenic complication. Experimental studies over recent years, in particular a pharmacokinetic study of the elimination of aminoglycosides, have enabled the authors to define rules of prescription for parenteral aminoglycosides designed to reduce to a minimum the risk associated with their use. New aminoglycosides such as Netromycin appear to be associated with reduced toxicity. The medico-legal consequences of this complication are still rare, although more precise rules of prescription tend to make the experts more rigorous. The experimental evidence of cochleovestibular toxicity of aminoglycosides applied locally in the presence of a perforated tympanum leaves no room for doubt. The principal factor seems to be the duration of treatment. The prescription of a local aminoglycoside in the presence of a perforated tympanum would only appear to be justified from a legal point of view when absolutely indicated by antibiotic sensitivity tests.

[Bilateral deafness due to the local use of framycetin (author's transl)]. / Surdité bilatérale due à la framycétine utilisée par voie locale.

A case is reported of total bilateral cochleo-vestibular destruction following instillation of Framycetin into the middle ear, under pressure, through a transtympanic drain. Toxicity of Framycetin after local use is exceptional and only one case, reported by Ransome, was found in the published literature. The interest of this observation is that, by using puncture of the foot of the stapes, it was possible to find Framycetin in the perilymphatic liquid three weeks after the injection of the product.

Contact allergy to neomycin sulfate: results of a multifactorial analysis.

PURPOSE: To perform a comprehensive, multifactorial analysis of potential risk factors (demographic and clinical) for contact allergy to neomycin sulfate, a common adverse reaction resulting from the topical use of this drug; especially in some subgroups of the population. METHODS: Retrospective analysis of allergy test data of the Information Network of Departments of Dermatology (IVDK, www.ivdk.org) between 1998 and 2003, including all patients patch tested with a standard screening series because of suspected allergic contact dermatitis (ACD). As one outcome, a positive (allergic) test reaction to neomycin sulfate was considered. An alternative outcome included only those patients with a positive test to neomycin sulfate and a final diagnosis of ACD. The association between outcome and potential risk factors was analyzed with Poisson regression analysis, deriving prevalence ratios (PR) as risk estimates. RESULTS: Of the 47,559 patients tested, 2.5% had positive reactions to neomycin sulfate, while in 1.1% ACD was additionally diagnosed. The results of the multifactorial analysis indicated that the risk of both outcomes decreased slightly during the period covered; was higher among patients with leg dermatitis; varied significantly with age and increased progressively with the number of additional positive reactions to other standard series allergens. Cross-reactivity to other, selectively tested, aminoglycoside antibiotics was substantial (kappa = 0.67; 95%CI: 0.63-0.71) for framycetin sulfate, to low (kappa = 0.33; 95%CI: 0.27-0.37) for gentamicin sulfate. CONCLUSIONS: The prevalence of contact sensitization to neomycin sulfate was noteworthy among patients patch tested in the IVDK centers. Supplementing clinical epidemiology, neomycin contact allergy has been estimated to be relatively common even on the level of the unselected population (prevalence approx. 1%). Hence, the topical use of neomycin sulfate by patients should be carefully monitored, considering its potential to induce ACD, with emphasis on subgroups at risk.

Incidence of neomycin and framycetin sensitivity.

A total of 450 consecutive patients were patch-tested to both neomycin and framycetin (20% in petrolatum). Thirteen patients were sensitive to both preparations, 10 to neomycin alone and four to framycetin alone. The significance of these results is discussed, with particular reference to the constituents of the preparations and the allergenic groups involved.

Deafness after treatment with ear drops containing neomycin, gramicidin and dexamethasone. A case report.

We describe a patient with a polyethylene tube to the middle ear who developed severe deafness and vertigo after treatment with ear drops where neomycin B was considered to be the most likely offending agent. High concentration of this antibiotic in the ear drops and access of the solution to the round window membrane in the absence of inflammatory edema and secretion may have been significant factors contributing to this serious side effect. Less ototoxic preparations should be used in patients with perforated tympanic membranes or grommets.

Contact hypersensitivity in patients with chronic otitis externa.

Thirty-seven patients with chronic otitis externa were investigated for contact hypersensitivity to 49 agents using standardized patch testing. Positive reactions were found in 22 (58%) patients. This incidence is higher than the 40% found in the only previous similar study and is within the range of 32-72% found in patients with contact dermatitis. The average age of subjects showing sensitivity was 56.7 years compared with 34.9 years for those with negative tests. This significant age difference suggests that contact hypersensitivity is not an aetiological factor in the younger patient. There was no significant difference in the duration of otitis externa between those with positive and negative tests. This feature has not been previously examined or reported. Neomycin was the commonest sensitizing agent, sensitization occurring in 12 (32%) patients.

Ototoxicity of ear drops: a clinical perspective.

Although experimental data confirm the presence of ototoxicity due to topical ear drops, the clinical relevance still remains debatable. Only few case reports document sensorineural hearing loss (SNHL) attributable to ototopical preparations in patients with chronic otitis media. A careful review of 134 patients charts evaluated between 1953 and 1995 for possible antibiotic related ototoxicity revealed two patients with bilateral profound SNHL attributable to excessive administration of framycetin- and polymyxin-containing ear drops in the presence of tympanic membrane perforation. Although ototopical preparations are widely used, they rarely induce SNHL. The authors emphasize patient education, application of topical ear drops using soaked gauze strips, and documentation of the patients hearing status at the beginning of the treatment regimen.

Allergy due to topical medications in chronic otitis externa and chronic otitis media.

Thirty-four patients suffering from chronic otorrhoea were tested for delayed type contact allergy. Patch testing showed a relevant positive reaction in 19 patients (56%). The most frequent allergens were aminoglycosides with neomycin and framycetin as major offenders. Other antimicrobial agents (clioquinol, polymyxin B), cream bases (lanolin) and corticosteroids (tixocortol) were less common allergens encountered. These results indicate that it is almost obligatory to perform patch testing in any patient with long-standing otitis which does not respond to local therapy. Scoring of the patch tests has to be extended to 7 days, as notably the aminoglycosides and corticosteroids only become positive after such a long interval. Because of the high risk of sensitization, topical preparations containing neomycin and framycetin should not be used routinely. We recommend the use of either a topical antiseptic or a topical antibiotic with low allergenic potential for the initial treatment of otorrhoea.