Approach to Sudden Hearing Loss Among Primary Care Physicians in Riyadh, Saudi Arabia.

INTRODUCTION: A medical emergency known as sudden sensorineural hearing loss (SSNHL) affects the ears suddenly, has a considerable probability of negative cognitive and functional outcomes, and can influence the patient's quality of life. Primary care physicians play a crucial role in diagnosing SSNHL and initiating prompt and efficient management since they are the ones who would likely encounter it initially. This study aims to evaluate the present knowledge, diagnostic, and management perspective of SSNHL among primary care physicians in Riyadh, Saudi Arabia. METHODS: A self-generated questionnaire with 17 questions was developed, and a link to the online survey was delivered to primary care physicians (PHPs) in Riyadh, Saudi Arabia, concerning the management of SSNHL. RESULTS: The knowledge level regarding SSNHL was evaluated, in which 21 (25%) of the participants had a low knowledge level, 34 (40.5%) had moderate knowledge, and 29 (34.5%) had a high knowledge level. Among 84 participants, 20 (23.8%) were confident in their ability to administer and understand the findings of tuning fork tests (TFT) to differentiate between sensorineural hearing loss and conductive hearing loss, whereas 64 (76.2%) were unsure about it. In addition, to distinguish between sensorineural hearing loss and conductive hearing loss, 62 (73.8%) participants were confident, and 22 (26.2%) participants were skeptical about their ability to interpret a formal audiogram. CONCLUSION: Considering SSNHL as a medical emergency, in our survey, many family doctors would make proper referral and treatment decisions. However, TFTs were underutilized for guiding management decisions compared to other ways to distinguish between conductive and sensorineural hearing loss.

Assessment of Knowledge, Attitude, and Practice of First Aid Management of Choking Among Primary School Teachers in Riyadh, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Understanding first aid is crucial for immediate intervention during health emergencies, with choking representing a significant danger, particularly for young children. Obstructed airways commonly lead to choking incidents, carrying substantial risks if not swiftly dealt with. This research endeavors to evaluate the comprehension, perspectives, and implementation of first aid measures for choking incidents among primary school teachers in Riyadh, Saudi Arabia, an area of paramount importance with minimal existing research within this particular demographic. METHODOLOGY: This was a cross-sectional study conducted from the beginning of July till the end of October 2023, among 447 primary school teachers in Riyadh, Saudi Arabia. Data collection was carried out by administering a questionnaire through an online platform. The questionnaire included demographic information, knowledge about signs and symptoms of choking, the attitude of participants, participant's practice, and the relationship between the knowledge level about choking and practice. The data collected were reviewed, coded, and then fed into IBM SPSS Statistics for Windows, Version 29 (Released 2023; IBM Corp., Armonk, New York, United States).  Results: Our study on first aid management of choking among primary school teachers highlighted significant findings. Participants demonstrated high awareness of choking signs with 386 (86.3%) recognizing universal signs and 330 (73.8%) claiming proficiency in first aid. Attitudes favored the importance of immediate treatment in 394 participants (88.1%) and the necessity of first aid knowledge for teachers (92.2%). One-hundred and fifty-one participants (33.8%) reported performing choking first aid with 328 (73.4%) opting for the Heimlich maneuver for a six-year-old. Significantly, higher knowledge correlated with increased first aid performance (p < 0.001) and support for mandatory training (p < 0.001). CONCLUSION: Our study indicates a higher knowledge level in primary school teachers with positive attitudes and practices regarding choking first aid management. It underscores the importance of enhancing first aid training among primary school teachers, emphasizing its positive impact on choking management and the necessity of immediate intervention in such cases.

Guidelines for cochlear implantation in Saudi Arabia.

This study aim to establish unified clinical practice guidelines (CPGs) for adults and pediatric cochlear implantation (CI) for the Ministry of Health specialist hospitals in the Kingdom of Saudi Arabia. A comprehensive literature review was carried out by a task force group. Guidelines were based on evidence-based medicine including institutions and individuals' experiences. Bilateral CI is recommended for adults and pediatrics with bilateral severe/profound hearing loss. The minimum age of implantation for children is recommended at 9 months. This study provides a safe framework for the multidisciplinary team to select appropriate CI candidates. It is important to establish a comprehensive multidisciplinary team covering different aspects of health care providers.

Evaluation of the efficacy, safety, and stability of posterior chamber phakic intraocular lenses for correcting intractable myopic anisometropic amblyopia in a pediatric cohort.

BACKGROUND: Myopic anisometropic amblyopia in pediatrics is one of the most challenging clinical situations that can face an ophthalmologist. Conventional correction modalities for myopic anisometropia, using spectacles, contact lenses, and/or occlusion therapy, may not be suitable for some pediatric patients or for some ocular conditions. This may lead to the development of anisometropic amblyopia. The aim of the present study was to evaluate the visual and the refractive efficacy, safety, and stability of Posterior Chamber Phakic Intraocular Lenses (PC-pIOLs) for correcting myopic anisometropic amblyopia in a pediatric cohort. METHODS: This case series, prospective, interventional study was conducted at Watany Eye Hospital, Cairo, Egypt. It comprised children and teenagers with myopic anisometropic amblyopia and unsuccessful conventional therapy. After implantation of Intraocular Collamer Lenses "ICLs" (Visian ICL, Model V4c, STAAR Surgical, Monrovia, California, USA), postoperative follow-up visits were scheduled, with automated refraction and Pentacam imaging performed. RESULTS: The study enrolled 42 eyes of 42 patients. The age range was 3 to 18 years (mean ± SD = 10.74 years ±4.16). The mean preoperative spherical equivalent (SE) was - 12.85 D ± 2.74. The results declared a significant improvement in the postoperative Corrected Distance Visual Acuity "CDVA" (P value < 0.01) and SE (P value < 0.01). The efficacy index had a value of 1.18 ± 0.3 and the safety index was 1.09 ± 0.24. The follow-up visits had a mean ± SD of 14.67 months ±16.56 (range of 1 to 54 months). The results showed a refractive stability, with statistically insignificant improvements in the patients' visual acuity and refractive status on evaluating the enrolled pediatrics during the follow-up visits compared to the first postoperative visits. No postoperative complications were encountered. Worthy of mention is that there was a significant (80%) non-compliance with the prescribed postoperative occlusion therapy. CONCLUSIONS: The present study, with the longest reported follow-up range, declared the long-term efficacy, safety, and stability of Visian ICLs for correcting myopic anisometropic amblyopia in pediatrics. The reported non-compliance with occlusion therapy validates the early implantation of Visian ICLs in cases with failed conventional therapy to guard against anisometropic amblyopia.

Malignant Otitis Externa in a 20-Year-Old Male Patient With Erdheim-Chester Disease: A Case Report.

Malignant otitis externa (MOE) is an uncommon, potentially life-threatening, invasive infection of the external auditory canal and lateral skull base. It is mainly seen in older adults with diabetes or immunocompromised patients and rarely seen in children. Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis disorder. It is a multisystem disease with a poorly understood etiology. It commonly affects the skeletal system, central nervous system (CNS), cardiovascular system, lungs, retroperitoneum, kidneys, and skin. CNS involvement confers poor prognosis and reduced response to treatment. Cardiovascular involvement is another indicator of poor prognosis. This report describes the case of a 20-year-old male with ECD who had bilateral malignant otitis externa/skull base osteomyelitis and hearing loss. The patient was not responding well to treatment. He was on intravenous antibiotics, underwent left mastoidectomy, received targeted immunotherapy, and had four rounds of chemotherapy. The patient died after six months from the diagnosis and targeted treatment, which indicates the aggressiveness of the disease. MOE should be suspected in any patient presenting with intractable otalgia with otorrhea that is not responsive to local treatment for uncomplicated otitis externa or otalgia with temporomandibular joint (TMJ) pain aggravated by chewing. This is the first report of malignant otitis externa in a young patient with ECD to the best of the author's knowledge. This case emphasizes the importance of suspecting MOE in young patients, especially if the risk factors of the disease are present because early diagnosis can prevent or minimize life-threatening complications.

Comparative Genomics and Metabolomics Analyses of Clavulanic Acid-Producing Streptomyces Species Provides Insight Into Specialized Metabolism.

Clavulanic acid is a bacterial specialized metabolite, which inhibits certain serine ß-lactamases, enzymes that inactivate ß-lactam antibiotics to confer resistance. Due to this activity, clavulanic acid is widely used in combination with penicillin and cephalosporin (ß-lactam) antibiotics to treat infections caused by ß-lactamase-producing bacteria. Clavulanic acid is industrially produced by fermenting Streptomyces clavuligerus, as large-scale chemical synthesis is not commercially feasible. Other than S. clavuligerus, Streptomyces jumonjinensis and Streptomyces katsurahamanus also produce clavulanic acid along with cephamycin C, but information regarding their genome sequences is not available. In addition, the Streptomyces contain many biosynthetic gene clusters thought to be "cryptic," as the specialized metabolites produced by them are not known. Therefore, we sequenced the genomes of S. jumonjinensis and S. katsurahamanus, and examined their metabolomes using untargeted mass spectrometry along with S. clavuligerus for comparison. We analyzed the biosynthetic gene cluster content of the three species to correlate their biosynthetic capacities, by matching them with the specialized metabolites detected in the current study. It was recently reported that S. clavuligerus can produce the plant-associated metabolite naringenin, and we describe more examples of such specialized metabolites in extracts from the three Streptomyces species. Detailed comparisons of the biosynthetic gene clusters involved in clavulanic acid (and cephamycin C) production were also performed, and based on our analyses, we propose the core set of genes responsible for producing this medicinally important metabolite.

In vivo functional analysis of a class A ß-lactamase-related protein essential for clavulanic acid biosynthesis in Streptomyces clavuligerus.

In Streptomyces clavuligerus, the gene cluster involved in the biosynthesis of the clinically used ß-lactamase inhibitor clavulanic acid contains a gene (orf12 or cpe) encoding a protein with a C-terminal class A ß-lactamase-like domain. The cpe gene is essential for clavulanic acid production, and the recent crystal structure of its product (Cpe) was shown to also contain an N-terminal isomerase/cyclase-like domain, but the function of the protein remains unknown. In the current study, we show that Cpe is a cytoplasmic protein and that both its N- and C-terminal domains are required for in vivo clavulanic acid production in S. clavuligerus. Our results along with those from previous studies allude towards a biosynthetic role for Cpe during the later stages of clavulanic acid production in S. clavuligerus. Amino acids from Cpe essential for biosynthesis were also identified, including one (Lys89) from the recently described N-terminal isomerase-like domain of unknown function. Homologues of Cpe from other clavulanic acid-producing Streptomyces spp. were shown to be functionally equivalent to the S. clavuligerus protein, whereas those from non-producers containing clavulanic acid-like gene clusters were not. The suggested in vivo involvement of an isomerase-like domain recruited by an ancestral ß-lactamase related protein, supports a previous hypothesis that Cpe could be involved in a step requiring the opening and modification of the clavulanic acid core during its biosynthesis from 5S precursors.

Adherence to Canada's Food Guide recommendations among Alberta's multi-ethnic youths is a major concern: findings from the WHY ACT NOW project.

BACKGROUND: Dietary habits formed during youth may result in the development of obesity and chronic diseases in adulthood. We aimed to determine the frequency of the consumption of foods and beverages and the degree of adherence to Canada's Food Guide recommendations among multi-ethnic youths. METHODS: Participants were recruited from 12 schools in the Edmonton, Alberta area by use of posters, school newsletters and advertisements. A 30-item food frequency questionnaire was administered by a trained interviewer to assess dietary intake in a convenience sample of 557 (328 females and 229 males) youths aged 11-23 years; for the purpose of the present study, only the 14-18 years age group was considered in the analysis. Participants were divided by sex and self-identified ethnicity into four groups [Indigenous, African & Middle Eastern (AME), Asian, and European]. Statistical analysis of the data was undertaken using t-tests, Welch's analysis of variance and Games-Howell tests. P < 0.05 was considered statistically significant. RESULTS: Vegetables and Fruit recommendations were the least likely to be followed, with 90.7-96.8% of participants in all groups not consuming the recommended number of servings day-1 . The mean frequency of fruit consumption was lower among Indigenous youths compared to Asian youths (0.90 versus 1.37 times day-1 ). A greater proportion of males than females (55.9% versus 44.3%) did not meet the minimum recommendations for Meat and Alternatives (P = 0.016). The percentage of youths not adhering to recommendations for Milk and Alternatives was 81.7% for Indigenous, 73.3% for AME, 78.6% for Asian and 63.5% for European youths. Indigenous youths more frequently consumed potato chips and soft drinks compared to other ethnic youths. The most frequently consumed beverage was milk (1.25 times day-1 ). CONCLUSIONS: The majority of youths did not consume minimum daily recommended servings of Vegetables and Fruit, Milk and Alternatives, and/or Meat and Alternatives food groups. Evidence-based dietary interventions and public health strategies are needed.

Association of work productivity with clinical and patient-reported factors in patients infected with hepatitis C virus.

Patients with HCV infection have reduced work productivity (WP), in terms of both presenteeism (impairment in work productivity while working) and absenteeism (productivity loss due to absence from work). The aim of this study was to identify clinical and patient-reported factors that are predictive of WP in HCV-infected patients. HCV-infected patients enrolled in clinical trials completed 3 PRO questionnaires (CLDQ-HCV, SF-36 and FACIT-F) and one work productivity (WPAI:SHP) questionnaire. In employed subjects, work productivity and its absenteeism and presenteeism components were calculated using WPAI:SHP instrument. Of 4121 HCV-infected patients with work productivity data, 2480 (60.2%) reported to be employed, and of those, 2190 had completed all PRO questionnaires before treatment initiation. Of the study cohort, 519/2190 (23.7%) had severe work impairment. In multiple linear regression analysis, work productivity was predicted by lower scores in activity/energy domain of CLDQ-HCV, physical well-being domain of FACIT-F, worry domain of CLDQ-HCV and role physical domain of SF-36 (all P < 0.0005). Furthermore, presenteeism was independently predicted by the activity/energy of CLDQ-HCV, physical well-being of FACIT-F, worry domain of CLDQ-HCV, role physical scale of SF-36 and fatigue scale of FACIT-F (P < 0.002). Finally, absenteeism was independently predicted by physical well-being scale of FACIT-F and role physical scale of SF-36 (all P < 0.002). Clinically, work productivity impairment was predicted by the presence of cirrhosis, anxiety, depression and clinically overt fatigue (P < 0.01). Thus, the most important drivers of WP in HCV are impairment of physical aspects of PROs and clinical history of depression, anxiety, fatigue and cirrhosis.

Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels.

The interaction of lipoproteins with hepatitis C virus (HCV) has pathogenic and therapeutic implications. Our aim was to evaluate changes in the apolipoprotein profile of patients with chronic hepatitis C during and after successful cure with ledipasvir and sofosbuvir (LDV/SOF) with and without ribavirin (RBV). One hundred HCV genotype 1 patients who had achieved SVR-12 after treatment with 12 weeks of LDV/SOF ± RBV were selected from the ION-1 clinical trial. Frozen serum samples from baseline, end of treatment and week 4 of follow-up were used to assay apolipoproteins (apoAI, apoAII, apoB, apoCII, apoCIII, apoE) using the Multiplex platform to assess for changes in the apolipoprotein levels. At the end of treatment compared to baseline, a significant reduction in apoAII levels (-14.97 ± 63.44 µg/mL, P = 0.0067) and apoE levels (-4.38 ± 12.19 µg/mL, P < 0.001) was noted. These declines from baseline in apoAII (-16.59 ±66.15 µg/mL, P = 0.0075) and apoE (-2.66 ± 12.64 µg/mL, P = 0.015) persisted at 4 weeks of post-treatment follow-up. In multivariate analysis, treatment with LDV/SOF + RBV was independently associated with reduction in apoE (beta = 5.31 µg/mL, P = 0.002) (compared to RBV-free LDV/SOF) (P < 0.05). In contrast, apoCII levels overall increased from baseline to end of treatment (+2.74 ±11.76 µg/mL, P = 0.03) and persisted at 4 weeks of follow-up (+4.46 ± 12.81 µg/mL from baseline, P = 0.0005). Subgroup analysis revealed an increase in apoCII during treatment only in patients receiving LDV/SOF without RBV (+5.52 ± 11.92 µg/mL, P = 0.0007) but not in patients receiving LDV/SOF + RBV (P = 0.638). Treatment with LDV/SOF ± RBV is associated with a persistent reduction in the apolipoprotein AII and E after achieving cure. These data suggest that treatment with LDV/SOF ± RBV may be associated with alterations in serum apolipoproteins which could potentially impact viral eradication.

The patient's journey with chronic hepatitis C from interferon plus ribavirin to interferon- and ribavirin-free regimens: a study of health-related quality of life.

BACKGROUND: Interferon and ribavirin negatively impact health-related quality of life (HRQL) during treatment. AIM: To compare the impact of interferon and/or ribavirin-containing regimens on HRQL to interferon- and ribavirin-free regimens. METHODS: HRQL data from nine multinational phase 3 clinical trials of sofosbuvir (SOF)-based regimens with and without ledipasvir (LDV), pegylated interferon (IFN) or ribavirin (RBV) were used. The Short Form-36 (SF-36) HRQL questionnaire was administered to subjects prospectively at baseline, during treatment, and 12 and 24 weeks after treatment cessation. RESULTS: A total of 3460 CH-C with SF-36 data were included (52.2 ± 10.3 years, 62.6% male, 73.6% treatment-naïve, 15.0% cirrhotic, 68.2% HCV genotype 1 and 20.1% genotype 3). Compared to baseline HRQL, at the end of treatment, severe HRQL decrements were noted in IFN + RBV ± SOF regimens (on average, -3.8 to -24.3 on a 0-100 scale for different HRQL domains), while moderate decrements were noted in SOF + RBV ± LDV (-2.8 to -8.6). In contrast, in SOF/LDV without RBV, HRQL improvements were noted during treatment (+2.3 to +5.2). By 12 weeks post-treatment, HRQL returned to baseline in IFN + RBV ± SOF (P > 0.05) and improved in all IFN-free arms (+2.6 to +7.8). In multivariate analysis, a lower end of treatment HRQL was associated with IFN + RBV + SOF and a higher end of treatment HRQL was associated with SOF/LDV. By post-treatment-12, SOF/LDV was additionally associated with higher mental health scores. These improvements in HRQL scores were maintained 24 weeks post-treatment. CONCLUSIONS: Removing interferon and ribavirin has led to substantial improvement of health-related quality of life during treatment. This may result in better patient experience and higher adherence to treatment regimen.

Patients' preferences and health utility assessment with SF-6D and EQ-5D in patients with chronic hepatitis C treated with sofosbuvir regimens.

BACKGROUND: Health utilities measure patients' preferences for a health state. AIM: To assess health utilities for sofosbuvir-containing therapy for chronic hepatitis C. METHODS: The SF-6D utility scores were derived from the SF-36 instrument administered at baseline, during and post-treatment to participants of the previously reported clinical trials of sofosbuvir. EQ-5D utility scores were also approximated from the SF-36 using a regression model. RESULTS: Nine hundred and ninety-four patients were enrolled. Baseline SF-6D and EQ-5D scores were 0.66 ± 0.13 and 0.71 ± 0.22, respectively (the POSITRON trial), 0.71 ± 0.16 and 0.76 ± 0.23 (FISSION), 0.70 ± 0.14 and 0.75 ± 0.22 (FUSION), 0.72 ± 0.15 and 0.79 ± 0.22 (NEUTRINO). In all studies, SF-6D and EQ-5D scores were highly correlated with each other. (r = 0.83-0.87, P < 0.0001). After 12 weeks, patients receiving sofosbuvir + ribavirin (POSITRON) had similar utility scores to placebo (P > 0.05). Patients receiving 12 and 16 weeks of sofosbuvir + ribavirin (FUSION) had similar utility scores (P > 0.05). In FISSION, patients receiving sofosbuvir + ribavirin had significantly better utilities compared to patients receiving interferon + ribavirin (P < 0.001). Patients receiving sofosbuvir + ribavirin + interferon (NEUTRINO) had a decrease in utilities during treatment (SF-6D: from 0.72 to 0.62, EQ-5D: 0.79 to 0.65; P < 0.0001) similar to that observed in patients receiving pegylated interferon + ribavirin for 24 weeks in FISSION (0.72 to 0.62 and 0.77 to 0.65, respectively, P < 0.0001). After 12 weeks post-treatment, patients with SVR (FUSION) had improvement in SF-6D (+0.026 from baseline, P = 0.013) and EQ-5D (+0.043, P = 0.013). In multivariate analyses, baseline depression, anxiety, fatigue, insomnia and treatment-related anaemia were the most consistent predictors of utilities. CONCLUSIONS: Patients' health utilities are minimally impacted by sofosbuvir + ribavirin treatment, as compared to interferon-based, therapy regardless of treatment duration. Clinical trials' numbers: NCT01542788 (POSITRON), NCT01497366 (FISSION), NCT01604850 (FUSION), NCT01641640 (NEUTRINO).

Associations of chronic hepatitis C with metabolic and cardiac outcomes.

BACKGROUND: Chronic hepatitis C virus (CH-C) infection is associated with metabolic conditions such as insulin resistance and type 2 diabetes (DM) and may increase the risk of cardiovascular diseases. AIM: To assess the association of CH-C with risk factors for cardiovascular diseases using US population data. METHODS: The National Health and Nutrition Examination Surveys (NHANES) collected between 1999 and 2010 were used. RESULTS: Of 19 741 participants considered eligible for the study. Of this cohort, 173 individuals (0.88%) had detectable HCV RNA and were considered to have CH-C. Compared with controls, CH-C patients were predominantly African American (23.5% vs. 10.5%, P < 0.0001), men (66.6% vs. 46.1%, P = 0.0001), more likely to be between 45 and 55 years of age (41.9% vs. 20.4%, P = 0.0001), had higher rate of insulin resistance (44.1% vs. 31.1%, P = 0.0301), hypertension (40.1% vs. 28.9%, P = 0.0201), and history of smoking (76.2% vs. 29.9%, P < 0.0001). In multivariate analysis, in addition to known risk factors for insulin resistance, CH-C was independently associated with the presence of insulin resistance [OR (95% CI) = 2.06 (1.19-3.57)], DM [OR = 2.31 (1.18-4.54)] and hypertension [OR = 2.06 (1.30-3.24)]. Independent predictors of cardiovascular diseases included older age, presence of obesity and smoking. CH-C was independently associated with congestive heart failure subtype of cardiovascular diseases but not ischaemic heart disease and stroke. CONCLUSION: Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes mellitus and hypertension) and congestive heart failure.

Quality of diabetes care in family health facilities in one health district in alexandria.

BACKGROUND: The aim of the present study was to evaluate the quality of service provided to type 2 diabetes in family health facilities in one Health District in Alexandria governorate. Also, the study aimed at assessing the difference in the quality of diabetes care between family health units and family health centers. MATERIAL AND METHODS: Records of 384 diabetic patients in 6 family health units and 3 family health centers were reviewed to abstract variables used to compute process and outcome performance measures for diabetes care. RESULTS: The level of performing process of care measures varied between individual measures with microalbuminuria testing done for 1.3% of the sample while smoking cessation counseling was done for all smokers. All measures were performed in family health centers in higher or equal percentage to family health units. Out of 14 cases who performed glycated hemoglobin test, one case from a family health center had value below 7%. The last measured systolic blood pressure was below 140 mm/Hg for 64.6% of all patients while the last measured diastolic blood pressure was less than 90 mm/Hg for 58.1% of all patients. The total cholesterol level was equal or less than 193 mg/dl for 50.5% of tested 194 patients. Outcome measures showed better control of blood pressure and cholesterol level in patients attended family health units than patients attended family health centers. CONCLUSION AND RECOMMENDATIONS: Diabetes care provided by family health facilities in Al-Montazah health district, Alexandria, was not conforming to diabetes practice guidelines for family physicians. Patient's co-payment might play a role in the low performance of expensive diabetes preventive services. It was recommended to adjust fee for diabetes preventive services according to patients' willingness to pay and to conduct further studies to investigate the effect of financing methods on the quality of care provided under the Egyptian Health Sector Reform Program.

A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment.

Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors. This phase II clinical trial assesses the dose, efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus (HCV). Chronic hepatitis C patients (n = 101) received pegylated interferon alpha-2b (1.5 mug/kg once weekly) and ribavirin (800-1400 mg once daily). Patients with anaemia [haemoglobin (Hb) /= 0.75 x 10(9)/L and <10 x 10(9)/L. During antiviral therapy, 52% of patients required darbepoetin alpha, filgrastim or both. Hb at the time of darbepoetin alpha initiation was 10.2 +/- 0.4 g/dL. After 81 days of darbepoetin alpha, Hb increased by 1.9 +/- 1.0 g/dL to 12.1 +/- 1.1 g/dL (P < 0.0001). Filgrastim resulted in a significant increase in ANC [0.75 +/- 0.16 x 109/L to 8.28 +/- 5.67 x 10(9)/L (P < 0.0001)]. In treatment-naïve patients, 48% achieved sustained virological response (SVR), whereas 27% of patients previously treated with a course of pegylated interferon alpha achieved SVR. Low viral load, nongenotype 1 and treatment with growth factors were independently associated with SVR. Mild and severe anaemia were associated with quality of life impairments. Darbepoetin alpha resulted in an improvement in the Vitality domain of Short Form-36. No significant adverse events were related to growth factors. During anti-HCV therapy, filgrastim improved neutropenia and darbepoetin alpha improved both anaemia and quality of life. Future randomized clinical trials are needed to establish the impact of growth factors in improving sustained virological response.

Effects of different mechanical treatments on nasal resistance assessed by rhinometry.

The goal of this study was to compare the effectiveness of three treatments aiming to reduce nasal airflow resistance (NR): an external nasal strip device (Respir+), an internal nasal mechanical dilator (Nozovent), and a topical decongestant (Pernazène). NR was estimated by active posterior rhinometry at both a 0.5 L/s flow (NRF) and a 1 cm H2O pressure (NRP), under four conditions: in the basal state, with Respir+, with Nozovent, and after treatment with Pernazène. The efficacy of each treatment was assessed by the percentage changes in NRF and NRP (%NRF and %NRP, respectively). The study was performed in 15 healthy subjects. The efficacy of the treatments was significantly different, depending on whether it was evaluated by NRF or by NRP (p<0.02), with %NRF and %NRP values, respectively, equal to the following: 88+/-20% and 91+/-14% with Respir+, 58+/-17% and 70+/-13% with Nozovent, and 55+/-29% and 69+/-22% with Pernazène. NRF remained unchanged with Respir+, whereas it significantly decreased with Nozovent and Pernazène (p<0.0001). No significant difference was observed between the effects of the two latter treatments. These results demonstrate that Nozovent, which involves no risk of side effects or drug interactions, is an effective treatment to improve nasal breathing. Nozovent might therefore be recommended as an alternative to topical decongestants, for certain subjects presenting with nasal obstruction.

Nasal airflow resistance measurement: forced oscillation technique versus posterior rhinomanometry.

This study was designed to determine whether nasal airflow resistance (Rn) which is nonlinear during tidal breathing, can be assessed by the forced oscillation (FO) technique. Rn values obtained by the FO technique and extrapolated to 0 Hz (Rn,FO) were compared to those assessed by posterior rhinomanometry at maximal tidal inspiratory flow (Rn,m), at a 0.5 L x s(-1) flow (Rn,F), and at a 1 hPa transnasal pressure (Rn,P). All Rn estimates were derived from the same inspiratory and expiratory nasal flow and transnasal pressure signals obtained during tidal nasal breathing whilst a forced flow was applied at the nose via a rigid nasal mask in 23 healthy volunteers, of whom 14 had additional measurements after vasoconstrictor treatment. In the basal state, no significant difference, and significant correlations (p<0.0001) were found between Rn,FO and the other Rn estimates. Only the regression line of Rn,FO versus Rn,m was not significantly different from the identity line. After nasal decongestion, Rn,P became significantly higher than the other Rn estimates (p<0.005). The regression line of Rn,FO versus Rn,m remained nonsignificantly different from the identity line. Similar results were observed regarding the percentage values of the different Rn estimates after decongestant treatment. This study shows that, despite its nonlinearity, Rn can be assessed by the FO technique, and that Rn,FO and Rn,m could be indifferently used as physiological indices of nasal patency. As the FO technique is more difficult to implement than the conventional rhinomanometry, its interest in rhinology appears not to be obvious.