Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response.

BackgroundThis retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval.MethodsEighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival.ResultsRetreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156).ConclusionOur data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed

Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C

Background/Aims: Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C. Methods: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. Results: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-a dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). Conclusions: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1

Experience with the use of Rituximab for the treatment of rheumatoid arthritis in a tertiary Hospital in Spain: RITAR study

There is evidence supporting that there are no relevant clinical differences between dosing rituximab 1000 mg or 2000 mg per cycle in rheumatoid arthritis (RA) patients in clinical trials, and low-dose cycles seem to have a better safety profile. Our objective was to describe the pattern of use of rituximab in real-life practice conditions. Methods: Rituximab for RA in clinical practice (RITAR) study is a retrospective cohort study from 2005 to 2015. Eligibility criteria were RA adults treated with rituximab for active articular disease. Response duration was the main outcome defined as months elapsed from the date of rituximab first infusion to the date of flare. A multivariable analysis was performed to determine the variables associated with response duration. Results: A total of 114 patients and 409 cycles were described, 93.0% seropositive and 80.7% women. Rituximab was mainly used as second-line biological therapy. On demand retreatment was used in 94.6% of cases versus fixed 6 months retreatment in 5.4%. Median response duration to on demand rituximab cycles was 10 months (interquartile range, 7–13). Multivariable analysis showed that age older than 65 years, number of rituximab cycles, seropositivity, and first- or second-line therapy were associated with longer response duration. The dose administered at each cycle was not significantly associated with response duration. Conclusions: Our experience suggests that 1000 mg rituximab single infusion on demand is a reasonable schedule for long-term treatment of those patients with good response after the first cycles, especially in seropositive patients and when it is applied as a first- or second-line biological therap

Tuberculosis retreatment 'others' in comparison with classical retreatment cases; a retrospective cohort review.

BACKGROUND: Many of the countries in sub-Saharan Africa are still largely dependent on microscopy as the mainstay for diagnosis of tuberculosis (TB) including patients with previous history of TB treatment. The available guidance in management of TB retreatment cases is focused on bacteriologically confirmed TB retreatment cases leaving out those classified as retreatment 'others'. Retreatment 'others' refer to all TB cases who were previously treated but with unknown outcome of that previous treatment or who have returned to treatment with bacteriologically negative pulmonary or extra-pulmonary TB. This study was conducted in 11 regional referral hospitals (RRHs) serving high burden TB districts in Uganda to determine the profile and treatment success of TB retreatment 'others' in comparison with the classical retreatment cases. METHODS: A retrospective cohort review of routinely collected National TB and Leprosy Program (NTLP) facility data from 1 January to 31 December 2010. This study uses the term classical retreatment cases to refer to a combined group of bacteriologically confirmed relapse, return after failure and return after loss to follow-up cases as a distinct group from retreatment 'others'. Distribution of categorical characteristics were compared using Chi-squared test for difference between proportions. The log likelihood ratio test was used to assess the independent contribution of type of retreatment, human immunodeficiency virus (HIV) status, age group and sex to the models. RESULTS: Of the 6244 TB cases registered at the study sites, 733 (11.7%) were retreatment cases. Retreatment 'others' constituted 45.5% of retreatment cases. Co-infection with HIV was higher among retreatment 'others' (70.9%) than classical retreatment cases (53.5%). Treatment was successful in 410 (56.2%) retreatment cases. Retreatment 'others' were associated with reduced odds of success (AOR = 0.44, 95% CI 0.22,0.88) compared to classical cases. Lost to follow up was the commonest adverse outcome (38% of adverse outcomes) in all retreatment cases. Type of retreatment case, HIV status, and age were independently associated with treatment success. CONCLUSION: TB retreatment 'others' constitute a significant proportion of retreatment cases, with higher HIV prevalence and worse treatment success. There is need to review the diagnosis and management of retreatment 'others'

Tuberculosis treatment in a refugee and migrant population: 20 years of experience on the Thai-Burmese border.

Although tuberculosis (TB) is a curable disease, it remains a major global health problem and an important cause of morbidity and mortality among vulnerable populations, including refugees and migrants

Femtosecond Laser-Assisted In Situ Keratomileusis Treatment of Residual Refractive Error following Femtosecond Laser-Enabled Keratoplasty.

Purpose:To evaluate the safety and effectiveness of femtosecond laser-assisted in situ keratomileusis (LASIK) in the treatment of residual myopia and astigmatism following femtosecond laser-enabled keratoplasty (FLEK). Design:Retrospective case review. Methods:Chart review of all patients with prior FLEK who subsequently underwent femto-LASIK surgery after full suture removal was performed at the Gavin Herbert Eye Institute at the University of California, Irvine. A total of 14 eyes in 13 patients met this criterion, and their comprehensive examinations performed at standard intervals were reviewed. Main outcome measures include uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) expressed as the logarithm of the minimum angle of resolution (logMAR), manifest refractive astigmatism, and spherical equivalent. Results:From the preoperative visit to the 3 month visit, all 14 eyes significantly improved in UDVA (logMAR, 0.93 ± 0.23 to 0.44 ± 0.32, P = 0.002) with no loss of CDVA (logMAR, 0.26 ± 0.19 to 0.18 ± 0.23, P = 0.50). All 14 eyes showed significant improvement in manifest refractive astigmatism (4.71 ± 1.77 to 2.18 ± 1.45 diopters (D), P = 0.003) and spherical equivalent (-2.57 ± 2.45 to -0.48 ± 0.83 D, P = 0.0007). There were no flap or graft complications as a result of femto-LASIK. Conclusions:Our findings suggest that femto-LASIK on eyes with prior FLEK is safe and effective in improving visual acuity and reducing residual astigmatism

Epithelial ingrowth following laser in situ keratomileusis (LASIK): prevalence, risk factors, management and visual outcomes

The number of laser in situ keratomileusis (LASIK) procedures is continuing to rise. Since its first application for correcting simple refractive errors over 25 years ago, the role of LASIK has extended to treat other conditions, including postkeratoplasty astigmatism/ametropia, postcataract surgery refractive error and presbyopia, among others. The long-term effectiveness, predictability and safety have been well established by many large studies. However, due to the creation of a potential interface between the flap and the underlying stroma, interface complications such as infectious keratitis, diffuse lamellar keratitis and epithelial ingrowth may occur. Post-LASIK epithelial ingrowth (PLEI) is an uncommon complication that usually arises during the early postoperative period. The reported incidence of PLEI ranged from 0%–3.9% in primary treatment to 10%–20% in retreatment cases. It can cause a wide spectrum of clinical presentations, ranging from asymptomatic interface changes to severe visual impairment and flap melt requiring keratoplasty. PLEI can usually be treated with mechanical debridement of the affected interface; however, additional interventions, such as alcohol, mitomycin C, fibrin glue, ocular hydrogel sealant, neodymium:yttriumaluminum garnet laser and amniotic membrane graft, may be required for recurrent or refractory cases. The aims of this review are to determine the prevalence and risk factors of PLEI; to describe its pathogenesis and clinical features and to summarise the therapeutic armamentarium and the visual outcome of PLEI

Patient-centered endodontic outcomes: a narrative review.

IntroductionRoot canal treatment (RCT) success criteria inform us of the path to bony healing and of prognostic factors, but tell little about how the patient perceives, feels, or values RCT. Patients choose, undergo, and pay for RCT, they live with the result, and inform their community. The purpose of this narrative review was to appraise patient-centered outcomes of initial non-surgical RCT and nonsurgical retreatment, in adults.Materials and methodsPatient-centered RCT outcome themes were identified in the extant literature: quality of life, satisfaction, anxiety, fear, pain, tooth survival and cost. Narrative review was applied because the disparate themes and data were unsuited to systematic review or meta-analysis.ResultsApplication of the Oral Health Impact Profile (OHIP) demonstrated that disease of pulpal origin affects quality of life with moderate severity, primarily through physical pain and psychological discomfort, and that RCT results in broad improvement of quality of life. Satisfaction with RCT is extremely high, but cost is the primary reason for dissatisfaction. Anxiety and fear affect RCT patients, profoundly influencing their behaviors, including treatment avoidance, and their pain experience. Fear of pain is "fair" to "very much" prior to RCT. Pain is widely feared, disliked, and remembered; however, disease of pulpal origin generally produces moderate, but not severe pain. RCT causes a dramatic decrease in pain prevalence and severity over the week following treatment. Survival rates of teeth after RCT are very high; complication rates are low. Cost is a barrier to RCT, but initial costs, lifetime costs, cost effectiveness, cost utility, and cost benefit all compare extremely well to the alternatives involving replacement using implants or fixed prostheses.ConclusionDentists must strive to reduce anxiety, fear, experienced and remembered pain, and to accurately inform and educate their patients with respect to technical, practical and psychosocial aspects of RCT

Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir with or without Ribavirin in Patients with HIV-HCV Coinfection. Real Life Interim Analysis of an Italian Multicentre Compassionate Use Program

Background and Aims: An HCV cure is now possible in a large proportion of HIV-HCV patient. We present real life results of a compassionate use program promoted by SIMIT (Infectious and Tropical Diseases Italian Society) of Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir ± Ribavirin for 12 weeks in 213 HIV-HCV genotype 1 patients. Data on efficacy and tolerability of this strategy in HIV patients have been reported until now only in 43 non cirrhotic HIV subjects

Hepatitis C virus resistance to the new direct-acting antivirals

Introduction: The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Areas covered: Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Expert opinion: Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.Fil: Esposito, Isabella. Hospital Universitario La Paz; EspañaFil: Trinks, Julieta. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Soriano, Vicente. Hospital Universitario La Paz; Españ