Extended treatment of treatment-naive patients with chronic hepatitis c virus (HCV) genotype 1-infection and slow response to pegylated interferon-alfa and ribavirin: a meta-analysis

Aims: Recently, several clinical trials analyzed if extended duration of treatment with pegylated interferon-alfa and ribavirin over 48 weeks can improve sustained virologic response (SVR) rates in HCV genotype 1-infected patients with slow virologic response. Because results of these clinical trials are conflicting, we performed a metaanalysis to determine the overall impact of extended treatment compared to standard treatment on virologic response rates in treatment-naive HCV genotype 1 slow responders. Methods: Literature search was performed independently by two observers using Pub Med, EMBASE, CENTRAL and abstracts presented in English at international liver and gastroenterology meetings. Randomized controlled clinical trials (RCTs; but studies that re-analyzed data retrospectively RCTs were also allowed) were considered if they included monoinfected treatment-naive HCV genotype 1 patients and compared treatment with pegIFN-alfa 2a or 2b in combination with ribavirin for 48 weeks versus extended treatment (up to 72 weeks) in slow responders. Primary and secondary end points were SVR rates and end-of-treatment (EOT) and relapse rates, respectively. In the present meta-analysis, study endpoints were summarized with a DerSimonian-Laird estimate for binary outcome basing on a random effects model. Results: Literature search yielded seven RTCs addressing the benefit of extended treatment with pegylated interferon-alfa and ribavirin in treatment-naive HCV genotype 1 slow responders. In total, 1330 slow responders were included in our meta-analysis. We show that extended treatment duration compared to the standard of care significantly improves SVR rates in HCV genotype 1 slow responders (12.4% improvement of overall SVR rate, 95% CI 0.055- 0.193, P = 0.0005). In addition, we show that rates of viral relapse were significantly reduced by extended treatment (24.1% reduction of relapse, 95% CI −0.3332 to −0.1487, P < 0.0001), whereas no significant impact of extended treatment on EOT response rates was found. Though extended treatment was burdened with an enhanced rate of premature treatment discontinuation due to interferonalfa- and ribavirin-related side effects, the frequency of serious adverse events was not increased. Conclusions: Treatment extension in HCV genotype 1 slow responders can improve SVR rates in difficult to treat patients and should be considered in patients who need to be treated before specific antivirals will be approved.

Mineralocorticoid Receptor Antagonism in the Treatment of Chronic Central Serous Chorioretinopathy : A Pilot Study.

PURPOSE:: Based on experimental data showing that central serous chorioretinopathy could result from overactivation of mineralocorticoid receptor pathway in choroid vessels, the authors studied eplerenone, a mineralocorticoid receptor antagonist, as a potential treatment for chronic central serous chorioretinopathy. METHODS:: This nonrandomized pilot study included 13 patients with central serous chorioretinopathy of at least 4-month duration, treated with 25 mg/day of oral eplerenone for a week followed by 50 mg/day for 1 or 3 months. The primary outcome measure was the changes in central macular thickness recorded by optical coherence tomography, and the secondary outcomes included changes in foveal subretinal fluid (SRF) measured by OCT, in best-corrected visual acuity (BCVA) and the percentage of eyes achieving complete resolution of subretinal fluid during the treatment period. RESULTS:: Central macular thickness decreased significantly from 352 ± 139 μm at baseline to 246 ± 113 μm and 189 ± 99 μm at 1 and 3 months under eplerenone treatment (P < 0.05 and P < 0.01, respectively). At 3 months, the subretinal fluid significantly decreased compared with baseline subretinal fluid (P < 0.01) and best-corrected visual acuity significantly improved compared with baseline best-corrected visual acuity (P < 0.001). CONCLUSION:: Eplerenone treatment was associated with a significant reduction in central macular thickness, subretinal fluid level, and an improvement in visual acuity. Randomized controlled trials are needed to confirm these encouraging results.

Premature epiphyseal closure in an adolescent treated by retinoids for acne: An unusual cause of anterior knee pain

Introduction.- Retinoids are effective and widely used for the treatment of severe acne. Their use can be, however, associated with numerous side effects. For example, some rare cases of premature epiphyseal closure were reported.Observation.- A sixteen-year-old soccer player consulted for bilateral progressive anterior knee pain, since two months, evoking a femoro-patellar origin. After physiotherapy, the pain decreases on the right but remained on the left. The history taking brought out the use of isotretinoin for more than 6 months (0.5 mg/kg). Magnetic resonance imaging (MRI) findings showed an irregularity of the growth plate and an important metaphyso-epiphyseal oedema, more marked on the left. The diagnosis of retinoid induced premature ephysieal closure was retained. The treatment was stopped, with a resolution of symptoms within two months. The control MRI of the left knee present persisting small sequelar thumbprint-like growth plate lesion. Eighteen months later, neither limb-length discrepancy nor static disorder was noticed.Discussion.- Premature epiphyseal closure is a rare complication of retinoid treatment of acne. Retinoids induce an invasion of the growth plate by osteoclasts and a decrease in proteoglycans synthesis. The knee seems the most involved joint. The clinical presentation is aspecific, sometimes lightly symptomatic. A careful pharmacological history and an appropriate imaging are necessary. MRI is now the gold standard. It shows an irregularity of the growth plate with an oedema on both sides. In chronic phase, a thumbprint-like image may persist. The symptoms resolution arises in few weeks after the treatment interruption. A single case of static disorder was reported until now. The small size of the growth plate interruptions, insufficient to lead to a growth disorder if the medicament is stopped early enough, explains probably it. This complication being rare, a radiological follow-up of the young patients treated by retinoids is not proposed.

Protocole pour l'évaluation et la prise en charge des plaies chroniques [Protocol for the evaluation and treatment of chronic wounds in the home care setting]

In 2001, it became evident that the domiciliary care nurses needed a tool to assist them in treating patients with chronic wounds. A protocol was therefore developed which could be used not only by the nurses but also by doctors and other health care professionals working in home care. As a parallel measure, a network of nurses specialised in wound care and available for advice and consultation was established.

Traitement chronique de l'hypertension arterielle par un inhibiteur de l'enzyme de conversion de l'angiotensine. [Chronic treatment of hypertension by an inhibitor of angiotensin converting enzyme]

Captopril, or SQ 14,225 an orally active inhibitor of angiotensin-converting enzyme, produced a significant blood pressure reduction in 26 hypertensives. This new drug, alone or combined with a diuretic, has normalized the blood pressure of the 22 patients on long-term treatment.

Eczéma chronique des mains: traitements conventionnels et nouveautés [Chronic hand eczema, conventional and new treatments].

Chronic hand eczema is a frequent cause of consultation. In Europe and Switzerland, it's one of the main reasons for patients to interrupt their profession. The etiology is pluri-factorial. Atopic patients are more likely predisposed. Pruritus, associated to pain and bleeding, is intense. Psychosocial consequences are huge, making this illness to an important public health problem. Topical treatment and UV-light are the main therapeutical strategy but the results are often disappointing. Recently, alitretinoine (9-cis retinoic acid) became the treatment of second choice with good response, allowing patients to preserve a good quality of life and their job.

A fresh look at interferon-alpha signaling and treatment outcomes in chronic hepatitis C.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFNalpha) and ribavirin. It achieves a sustained viral clearance in only 50-60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFNalpha. In patients with a rapid virological response to treatment, pegIFNalpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFNalpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.

Tailored thoracomyoplasty as a valid treatment option for chronic postlobectomy empyema.

BACKGROUND: Chronic post-lobectomy empyema is rare but may require space obliteration for infection control. We report our experience by using a tailored thoracomyoplasty for this specific indication with respect to infection control and functional outcome. METHODS: We retrospectively analyzed 17 patients (11 men, 6 women) with chronic postlobectomy empyema who were treated by thoracomyoplasty in our institution between 2000 and 2011. All patients underwent an initial treatment attempt by use of chest tube drainage and antibiotics except those with suspicion of pleural aspergillosis (n = 6). In 5 patients, bronchus stump insufficiency was identified at preoperative bronchoscopy. A tailored thoracoplasty was combined with a serratus anterior-rhomboid myoplasty, which also served to close a bronchopleural fistula, if present. The first rib was resected in 11 of 17 patients. RESULTS: The 90-day mortality was 11.7%. Thoracomyoplasty was successful in all surviving patients with respect to infection control, space obliteration, and definitive closure of bronchopleural fistula, irrespective of the type of infection, the presence of a bronchopleural fistula, or whether a first rib resection was performed. Postlobectomy pulmonary function testing before and after thoracoplasty revealed a mean predicted FEV(1) of 63.0% ± 8.5% and 51.5% ± 4.2% (p = 0.01) and a mean predicted DLCO of 59.8% ± 11.6% and 54.5% ± 12.5%, respectively. Postoperative shoulder girdle dysfunction and scoliosis were prevented in patients willing to undergo intense physiotherapy. CONCLUSIONS: Tailored thoracomyoplasty represents a valid option for patients with chronic postlobectomy empyema without requiring a preceding open window thoracostomy. Space obliteration and infection control were equally obtained with and without first rib resection.

Myofascial pain syndrome associated with trigger points: A literature review. (I): Epidemiology, clinical treatment and etiopathogeny

Over the last few decades, advances have been made in the understanding of myofascial pain syndrome epidemiology, clinical characteristics and aetiopathogenesis, but many unknowns remain. An integrated hypothesis has provided a greater understanding of the physiopathology of trigger points, which may allow the development of new diagnostic, and above all, therapeutic methods, as well as the establishment of prevention policies and protocols by the health profession. Nevertheless, randomized studies are needed to provide a better understanding and detection of the different factors involved in the origin of trigger points.

Treatment of osteitis pubis with on single iv injection of Ibandronate: report of two cases

Objectives: Osteitis pubis is a noninfectious painfulinflammatory disorder of the symphysis pubis. Etiologicfactors are numerous, the most common are: osseousextension of adductor enthesis due to sport overuse,irritation after urological and abdominal procedures, andsystemic inflammatory disorders in particular spondylarthropathies.Many cases are idiopathic. The symptomsconsist of regional chronic mechanical and sometimenocturnal pain. Diagnosis is usually confirmed by eitherbone scintigraphy or by MRI. There are no standardtreatments but conservative approaches including rest andNSAIDS are generally recommended. In 2001, a goodclinical and radiological response of three refractory caseswith 3-6 monthly perfusions of pamidronate was reported(1). Ibandronate is a much more powerful and long-lastingbisphosphonate than pamidronate, and has not yet beenreported in literature to our knowledge in this indication.Materials/Methods: We present two cases of idiopathicorigin: one woman (63 years old) and one man (36 yearsold).The symptoms were present >3 months in the firstpatient and 1 year in the second. The diagnosis wasconfirmed by MRI which showed bone edema on bothsizes of symphysis and in the second case bony erosionsadjacent to the joint were seen. Both cases failed to respondto conservative measures. Both patients received one singledirect iv Injection of 3 mg of Ibandronate.Results: The injections resulted in a rapid (within a fewdays) resolution of pain that lasted more than 6 months inboth patients. No side effects were observed. In the firstcase, an isotope bone scan performed 4 months after theinjection showed no residual uptake. The second patienthad a repeated MRI after 6 months. It demonstrated anattenuation of bone edema compared to the first MRI.Conclusions: IV Ibandronate may constitute a safe andeffective treatment option for patients with refractoryosteitis pubis.Reference: 1: Maksymowych WP, Aaron SL, Russell AS, JRheumatol 28:2754, 2001.Disclosure of Interest: None declared.

A comparison of the dental status and treatment needs of older adults with and without chronic mental illness in Sevilla, Spain

Objectives: To study the dental status and treatment needs of institutionalized older adults with chronic mental illness compared to a non-psychiatric control sample. Study Design: The sample size was 100, in which 50 were psychogeriatric patients (study group; SG) classified according to DSM-IV, with a mean age of 69.6 ± 6.7 years, and 50 non-psychiatric patients (control group; CG), with a mean age of 68.3 ± 6.9 years. Clinical oral health examinations were conducted and caries were recorded clinically using the Decayed, Missing and Filled Teeth Index (DMFT). Results were analyzed statistically using the Student"s t-test or analysis of variance. Results: Caries prevalence was 58% and 62% in SG and CG, respectively. DMFT index was 28.3 ± 6.6 in SG and 21.4 ± 6.07 in CG (p < 0.01). Mean number of decayed teeth was higher in SG (3.1) compared to CG (1.8) (p=0.047). Mean number of missing teeth were 25.2 and 16.4 in SG and CG respectively (p<0.05). DMFT scores were higher in SG in all the age groups (p < 0.01). Mean number of teeth per person needing treatment was 3.4 in SG and 1.9 in CG (p= 0.037). The need for restorative dental care was significantly lower in the SG (0.8 teeth per person) than in the CG (1.7 teeth per person) (p = 0.043). Conclusions: Institutionalized psychiatric patients have significantly worse dental status and more dental treatment needs than non-psychiatric patients.

IFN Stimulated Gene Expression in the Liver is a Better Predictor of Treatment Response in Chronic Hepatitis C than the IL28B (IFN lambda 3) Genotype

BACKGROUND: Therapy of chronic hepatitis C (CHC) with pegIFNα/ribavirin achieves a sustained virologic response (SVR) in ∼55%. Pre-activation of the endogenous interferon system in the liver is associated with non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. METHODS: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. RESULTS: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. CONCLUSIONS: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype.

Impact of soluble CD26 on treatment outcome and hepatitis C virus-specific T cells in chronic hepatitis C virus genotype 1 infection.

BACKGROUND: Interferon and ribavirin therapy for chronic hepatitis C virus (HCV) infection yields sustained virological response (SVR) rates of 50-80%. Several factors such as non-1 genotype, beneficial IL28B genetic variants, low baseline IP-10, and the functionality of HCV-specific T cells predict SVR. With the pending introduction of new therapies for HCV entailing very rapid clearance of plasma HCV RNA, the importance of baseline biomarkers likely will increase in order to tailor therapy. CD26 (DPPIV) truncates the chemokine IP-10 into a shorter antagonistic form, and this truncation of IP-10 has been suggested to influence treatment outcome in patients with chronic HCV infection patients. In addition, previous reports have shown CD26 to be a co-stimulator for T cells. The aim of the present study was to assess the utility of CD26 as a biomarker for treatment outcome in chronic hepatitis C and to define its association with HCV-specific T cells. METHODS: Baseline plasma from 153 genotype 1 and 58 genotype 2/3 infected patients enrolled in an international multicenter phase III trial (DITTO-HCV) and 36 genotype 1 infected patients participating in a Swedish trial (TTG1) were evaluated regarding baseline soluble CD26 (sCD26) and the functionality of HCV-specific CD8(+) T cells. RESULTS: Genotype 1 infected patients achieving SVR in the DITTO (P = 0.002) and the TTG1 (P = 0.02) studies had lower pretreatment sCD26 concentrations compared with non-SVR patients. Sixty-five percent of patients with sCD26 concentrations below 600 ng/mL achieved SVR compared with 39% of the patients with sCD26 exceeding 600 ng/mL (P = 0.01). Patients with sCD26 concentrations below 600 ng/mL had significantly higher frequencies of HCV-specific CD8(+) T cells (P = 0.02). CONCLUSIONS: Low baseline systemic concentrations of sCD26 predict favorable treatment outcome in chronic HCV infection and may be associated with higher blood counts of HCV-specific CD8(+) T cells.