RESUMEN

Artificial intelligence (AI) and machine learning (ML) are transforming industries, where low-cost, big data can utilize computing power to optimize system performance. Oil and gas (O&G) fields are getting mature, where well integrity (WI) problems become more common and field operations are now more challenging. Hence, they are good candidates for transformation due to the low cost of data storage, highlighting the oil market decline, along with dynamic risk posed during operations. This paper is presenting a comprehensive compilation of different ML applications in diverse disciplines of the petroleum industry. The pool of AI and ML with respect to different areas of applications along with publication years has been categorized. The main focus of this study is classifying well integrity failures where the authors found that the potential of AI and ML in predicting well integrity failures has not been efficiently tapped, and there is an explicit gap in the literature. First, the applications of AI, ML, and data analytics in the O&G industry are discussed thoroughly, so this paper can be a comprehensive reference for readers and future researchers. Then data preprocessing is explained. This includes data gathering, cleaning, and feature engineering. Next, the different ML models are compared and discussed. Finally, model performance evaluation and best model selection are described. This study would be a concrete foundation in the design and construction of ML programs that can be deployed for WI risk management. The developed model can be simply used for any well stock, providing quick and easy assessment instead of subjective and tedious assessment. The layout can be simply adjusted to reflect the risk profile of any well type or any field.

Asunto(s)

COVID-19 , Antivirales/uso terapéutico , Humanos , SARS-CoV-2

RESUMEN

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection in patients treated for chronic hepatitis C (HCV) with direct-acting antiviral agents has emerged recently as an important safety issue; however, it has not been adequately studied in pediatric age groups. We aimed to evaluate this risk in adolescent patients infected with chronic HCV and positive for HBsAg and HBcAbs. PATIENTS AND METHODS: One hundred and fifteen adolescent patients from 12 to 17 years of age, infected with chronic HCV and positive for HBcAbs with or without HBsAg were included in this study. All patients were treated with 1 tablet daily of the fixed-dose combination sofosbuvir/ledipasvir for 12 weeks. Patients were closely monitored throughout the study for virus load, liver functions, and other safety and efficacy outcome measures. RESULTS: The sustained virologic response 12 (SVR12) rates were 96.7% (95% confidence interval: 88.6-99.1%) in HBsAg positive group and 98.2% (95% confidence interval: 90.4-99.7%) in HBsAg negative with HBcAbs positive group. Throughout the treatment period and the 12 weeks follow-up after treatment, there has been no single case in both HBsAg negative or positive that showed any manifestation of reactivation of hepatitis B, detected levels of HBV-DNA, or deterioration of liver functions. CONCLUSION: No HBV reactivation was observed in adolescents treated for chronic HCV with direct-acting antiviral agents in our study, in both HBsAg positive or occult hepatitis B. Although results are reassuring, we still recommend close monitoring of liver functions to not miss even rare cases of such a potentially serious condition.

Asunto(s)

Antivirales , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B , Hepatitis C Crónica , Adolescente , Antivirales/efectos adversos , Antivirales/uso terapéutico , Niño , Coinfección , Femenino , Hepatitis B/complicaciones , Hepatitis B/fisiopatología , Hepatitis B/virología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/fisiopatología , Hepatitis C Crónica/virología , Humanos , Pruebas de Función Hepática , Masculino , Estudios Prospectivos , Activación Viral/efectos de los fármacos

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AIM: Follow-up of chronic hepatitis C virus (HCV) infection following Interferon (IFN) plus Ribavirin (RBV) or direct-acting antiviral (DAA) drug therapy in a cohort of paediatric outpatients as confirmed by a sustained virologic response (SVR). METHODS: This study included a cohort of 60 patients (6-18 years), divided into 2 groups: Group 1:21 patients who completed treatment with IFN/RBV. Group 2:39 treated with dual DAA therapy: 19 with Sofosbuvir/Ledipasvir (SOF/LED) and 20 with Sofosbuvir/Daclatasvir (SOF/DCV). RESULTS: Group 1:12 (57.1%) were cured, six were IFN/RBV treatment failure then subsequently treated with DAAs successfully, and three had liver transplants. IFN/RBV side effects were reported in all patients; however, fibrosis regressed in two cured patients. Group 2: all were cured. HCV RNA became negative in all DAAs-treated patients at weeks 2, 4 and 12 of treatment (100%) as well as SVR after 12 weeks (100%). Thirty patients reported no adverse side effects whereas only nine suffered minor side effects. CONCLUSIONS: In our cohort, SOF/LED therapy and SOF/DCV therapy were extremely safe and effective with 100% SVR and negligible short-term side effects. IFN/RBV therapy was much less effective (SVR 57.1%) and accompanied with short-term side effects. Fibrosis might stop and even regress with successful treatment.

Asunto(s)

Antivirales , Hepatitis C Crónica , Antivirales/uso terapéutico , Niño , Quimioterapia Combinada , Estudios de Seguimiento , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Resultado del Tratamiento

RESUMEN

BACKGROUND & AIMS: Treatment of children aged 3-6 genotype 4 is still limited by the interferon side effects. We aimed in this study to evaluate the effectiveness and safety of sofosbuvir/ledipasvir in children (3-6 years) genotype 4 chronic HCV-infected patients. METHODS: In total, 22 consecutive chronic HCV-infected patients (mean age 4.8 ± 0.9years, 19 males) were included in this prospective study. All patients received sofosbuvir 200 mg/ledipasvir 45 mg in a single oral daily dose. Patients were randomly subdivided into two groups according the duration of treatment into 8 and 12 weeks. All the clinical and laboratory data were collected. All the side effects were recorded from the patients or their parents. Follow-up were made at Week 4, 8 and 12 and 12 weeks after the end of treatment (SVR12). RESULTS: The overall SVR12 rate was 100%. At Week 4, 9/11 patients in the 12-week group (81.8%; 95% CI: 52.3%-94.7%) achieved virologic negativity, vs 10/11 (90.9%; 95% CI: 62.3%-98.4%) in the 8-week group. At Week 8, 10/11 (90.8%; 95% CI: 62.3%-98.4%) in the 12-week group vs 11/11 (100%; 95% CI: 74.1%-100%) in the 8-week group were virologically negative. The reported side effects were cough, abdominal pain, nausea, vomiting and diarrhoea especially early in the treatment. The main complaint was difficulty in swallowing the tablets in the youngest patient at the beginning of the course of treatment. All patients were compliant to treatment. CONCLUSION: Sofosbuvir/ledipasvir combination is safe and tolerable in the chronic infected HCV genotype 4 infected children (3-6 years). The 8-week treatment duration is similarly effective as the 12-week duration.

Asunto(s)

Hepatitis C Crónica , Sofosbuvir , Antivirales/efectos adversos , Bencimidazoles , Niño , Preescolar , Quimioterapia Combinada , Fluorenos/efectos adversos , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Estudios Prospectivos , Sofosbuvir/uso terapéutico , Resultado del Tratamiento

RESUMEN

BACKGROUND: Diabetic foot ulcer (DFU) is the main risk factor for nontraumatic lower-limb amputation. We hypothesized that by reversing the offending local tissue factors resulting from the low tissue supply of oxygen, inefficient fuel metabolism and acidosis, we can eradicate the infection and help to promote healing. This might be enhanced with the help of an innovated local preparation (PEDYPHAR®) through its enriched alkaline ointment base and the regenerating growth factors of Royal Jelly (RJ) plus the antimicrobial, immune-modulatory nutritional and other biochemical properties of RJ and Panthenol. We conducted this study to test the safety and efficacy of PEDYPHAR ointment as an adjuvant in limb salvage management for patients with limb-threatening diabetic foot wounds. METHODS: A prospective, randomized, controlled open-label study design with a mean follow-up period of 12 weeks. One hundred and nineteen eligible patients with diabetic foot wounds presenting to 3 outpatient clinics in Egypt were randomized to be treated with the local application of either PEDYPHAR or Panthenol ointment under dressing after conservative debridement of necrotic tissue and irrigation with warm normal saline. RESULTS: At the end of the 12-week follow-up period, PEDYPHAR showed a higher rate of complete healing of limb-threatening wounds in the intent-to-treat population, 11 of 34 (32.4%) in PEDYPHAR-treated group versus 3/25 (12%) in the Panthenol-treated (control) group (p=0.034* [*indicates it is statistically significant]). CONCLUSION: We can conclude that PEDYPHAR could be an effective and safe conservative local adjuvant treatment for cases of diabetic foot infection.Registration number in ClinicalTrials.gov: NCT01531517.

RESUMEN

BACKGROUND: Childhood cancer survivors are potentially at a higher risk of infection with hepatitis C virus (HCV). The effects of all-oral direct-acting antiviral therapy (DAA) on both the HCV infection as well as the state of cancer remission have not been well investigated in this population. AIM: To test the effects of dual sofosbuvir/daclatasvir (SOF/DCV) therapy in the treatment of chronic HCV in survivors of hematologic malignancy in pediatric age group. METHODS: We conducted a prospective, uncontrolled, open-label multicenter study. A total of 20 eligible, chronic HCV, genotype-4, infected children who had been in continuous complete remission from hematologic cancer (leukemia/lymphoma) for at least one year were included in the study. All patients were treated with combined SOF/DCV for 12 wk. Patients were monitored throughout the study till 12 wk after end of treatment for safety and efficacy outcomes including the sustained virologic response 12 (SVR12) rate, hematological indices, liver and kidney functions. RESULTS: The intent-to-treat SVR12 rate was 20 of 20 (100%; 95%CI: 84%-100%). All patients showed normalized liver enzymes from week-4. All hematological indices, liver and kidney functions were kept normal throughout the study. No fatalities or treatment-emergent serious or severe adverse events were reported throughout the study. CONCLUSION: SOF/DCV combined therapy could be used safely and effectively in the treatment of chronic HCV genotype-4 infection in leukemia/lymphoma treated children. No relapses were detected during treatment and throughout the follow up period for either the original malignant disease or the HCV infection.

RESUMEN

Negative effects on growth indices had been reported in children treated with interferon for chronic viral hepatitis. Forty chronic hepatitis C virus-infected adolescents, 12-17 years of age, were treated with sofosbuvir/daclatasvir therapy for 12 weeks. The intent-to-treat sustained virologic response rate at 12 weeks after end of treatment was 39/40 (97.5%). Unlike interferon-based therapy, we did not detect significant negative effects on linear growth or weight. Contrarily, a trend to increased appetite and insignificant weight gain was observed, but further larger studies are needed to confirm. See Video-Abstract, http://links.lww.com/ASAIO/A381.

Asunto(s)

Antivirales/efectos adversos , Desarrollo Infantil/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/efectos adversos , Sofosbuvir/efectos adversos , Adolescente , Antivirales/administración & dosificación , Estatura/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Carbamatos , Niño , Femenino , Humanos , Imidazoles/administración & dosificación , Masculino , Pirrolidinas , Sofosbuvir/administración & dosificación , Respuesta Virológica Sostenida , Resultado del Tratamiento , Valina/análogos & derivados

RESUMEN

BACKGROUND: The sustained virological response (SVR) rate for the 12-week sofosbuvir (SOF)/ledipasvir (LVD) treatment of adolescent genotype-4 patients is high. The aim of this study is to evaluate 8 versus 12-week treatment efficacy and safety in adolescent genotype-4 patients. PATIENTS AND METHODS: In total, 157 chronic hepatitis C-infected adolescent patients (mean age 14±2 years, 62% males) were included in this study. All patients received a morning dose of SOF (400 mg)/LVD (90 mg) as a single tablet for 8 and 12 weeks. Laboratory and biochemical monitoring were performed at weeks 4 and 8, end of treatment (8/12) and 12 weeks after the end of treatment (SVR12). RESULTS: In total, SVR12 was 98% [95% confidence interval (CI): 96-100] for all treated patients. For patients treated for 12 weeks, SVR12 was 97.6% (95% CI: 96-101) (82/84 patients), and 98.6% (95% CI: 93-101) (72/73) patients for those treated for 8 weeks. For both regimens, no serious adverse effects, treatment discontinuation or cases of death were detected. The main adverse effects for the 8-week patient group were fatigue (2.8%), headache (1.4%), nausea (1.4%) and epigastric tenderness (1.4%). For the 12-week-treated group, adverse events were epigastric tenderness (1.2%), nausea (1.2%), diarrhoea (2.4%) and rash (2.4%). Three patients were lost to follow-up: two were in the 12-week treatment group and one was in the 8-week group. All of them reached end of treatment but were lost before SVR12. No relapsers were observed in either group. CONCLUSION: Eight weeks of treatment of SOF/LVD combination is equally effective and safe as 12 weeks in adolescent genotype-4 patients.

Asunto(s)

Bencimidazoles/administración & dosificación , Fluorenos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Uridina Monofosfato/análogos & derivados , Administración Oral , Adolescente , Antivirales/administración & dosificación , Niño , Estudios Transversales , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/diagnóstico , Humanos , Hígado/diagnóstico por imagen , Masculino , Estudios Prospectivos , Sofosbuvir , Resultado del Tratamiento , Uridina Monofosfato/administración & dosificación

RESUMEN

OBJECTIVES: Dual sofosbuvir/daclatasvir (SOF/DCV) therapy is currently recommended by the European Association for Study of Liver (EASL) as an option for the treatment of chronic hepatitis C virus (HCV) infection in adults for all genotypes; however, it is still not considered for patients younger than 18 years old. We aimed to test safety and efficacy of SOF/DCV in adolescent patients 12 to 17 years old with chronic HCV, genotype 4 infection. METHODS: We conducted a prospective, uncontrolled, open-label multicenter study. A total of 30 chronic HCV-infected adolescents, aged from 12 to 17 years old were included and treated with dual SOF/DCV for 12 weeks. Patients were monitored throughout the treatment and follow-up period for safety and efficacy outcome measures including the sustained virologic response 12 (SVR12) rate. RESULTS: The intention-to-treat (ITT) SVR12 rate was 29 of 30 (96.7%; 95% confidence interval [CI] 83.3%-99.4%). The only patient who did not achieve SVR12 was lost to follow-up after showing viral negativity at the end of treatment (EOT) visit. Whereas all the remaining 29 patients (100%, 95% CI 88.3%-100%) who completed the follow-up visits achieved SVR12. All patients showed normalized liver enzymes with normal hematological, liver and renal function tests at the end of the study. No fatalities or treatment-emergent serious or severe adverse events were reported throughout the study. CONCLUSIONS: SOF/DCV combined therapy could be a safe and effective treatment in adolescent patients 12 to 17 years old with chronic HCV genotype 4 infection. (See Video, Supplemental Digital Content, http://links.lww.com/MPG/B348).

Asunto(s)

Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/uso terapéutico , Sofosbuvir/uso terapéutico , Adolescente , Antivirales/efectos adversos , Carbamatos , Niño , Quimioterapia Combinada , Femenino , Humanos , Imidazoles/efectos adversos , Masculino , Estudios Prospectivos , Pirrolidinas , Sofosbuvir/efectos adversos , Respuesta Virológica Sostenida , Valina/análogos & derivados , Carga Viral

RESUMEN

Recently, sofosbuvir and the fixed-dose combination of sofosbuvir/ledipasvir were approved for the treatment of chronic hepatitis C virus infection in adolescents, criteria being 12 years old and above or weighing at least 35 kg. Here we present the results of a pilot single cohort of 10 consecutive adolescent patients with chronic hepatitis C virus and treated with dual sofosbuvir/daclatasvir therapy for a response-tailored duration of 8 weeks for those who achieved very rapid virologic response (vRVR) and 12 weeks for those who did not. All patients achieved vRVR at week 2 and completed the shortened 8 weeks course. All patients (10/10) (100% [confidence interval 72.25-100%]) achieved sustained vRVR at week 12 post-treatment with good tolerability and no serious adverse events. These data could provide support to our suggested response-tailored protocol of dual therapy with sofosbuvir/daclatasvir in adolescents particularly for shortened duration in those who achieved vRVR. Further larger randomized controlled studies are recommended.

Asunto(s)

Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/administración & dosificación , Sofosbuvir/administración & dosificación , Adolescente , Antivirales/uso terapéutico , Carbamatos , Niño , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Imidazoles/uso terapéutico , Masculino , Proyectos Piloto , Estudios Prospectivos , Pirrolidinas , Sofosbuvir/uso terapéutico , Resultado del Tratamiento , Valina/análogos & derivados

RESUMEN

BACKGROUND: The most recent European Association for the Study of the Liver (EASL) 2016 Guidelines on treatment of hepatitis C (HCV), allowed for shortening the course of treatment for some subsets of patients with sofosbuvir/ledipasvir and with grazoprevir/elbasvir based on cutoff baseline HCV RNA values. We hypothesized that it would be prudent to also consider an objectively assuring very rapid, on-treatment, virologic response to therapy at week 2 (vRVR) before taking the decision of shortening the treatment duration. So we planned this study to test whether a dual sofosbuvir/daclatasvir (SOF/DCV) treatment duration tailored according to achieving vRVR to 8 or 12weeks is non-inferior to the recommended fixed 12weeks course in non-cirrhotic Egyptian chronic HCV genotype-4 patients. METHODS: The study was conducted in an outpatient setting according to a prospective, randomized, open-label, comparative, non-inferiority study design. A hundred twenty eligible, non-cirrhotic, chronic HCV patients were randomly assigned (1:1) to receive daily doses in the form of one Gratisovir 400mg table (generic sofosbuvir produced by Pharco Pharmaceuticals, Alexandria, Egypt) plus one Daktavira 60mg tablet (generic daclatasvir produced by Dawood Pharm, Egypt) for either a fixed 12weeks duration (reference group) or a response tailored duration (test group). In the test group the treatment duration was tailored according to the virus load tested by real time PCR into 8weeks for patients who had undetectable HCV RNA level in their serum by the end of the second week of treatment (vRVR)), or 12weeks for those who did not show vRVR. The primary outcome of the trial was the proportions of patients achieving SVR12 (HCV RNA below lower level of quantification at week 12 after end of treatment). The comparison between groups was based on testing the null hypothesis of inferiority of the response-tailored group with a pre-specified margin of non-inferiority (NI-m) of 0.1 (10%). The protocol was registered with a WHO Clinical Trial Registration ID: ACTRN12617000263392. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372041 FINDINGS: Starting from Jun, 5 2016, a hundred twenty eligible patients from 4 outpatient clinics in Alexandria, Egypt were randomized to either a fixed duration group (reference group: n=60 patients) or a response tailored duration group (test group: n=60 patients). During the whole period of the study, only 1 patient dropped-out from each group. Both were lost to follow-up after the 4th week's visit. Baseline characteristics in both groups were almost matching. Fifty eight out of the total 60 intention-to-treat (ITT) patients in the reference group achieved SVR12 (96.67% (95% confidence interval (CI): 88.64-99%). Whereas, 59 out of the total 60 (ITT) patients in the test group achieved SVR12 (98.33% (CI: 91.14-99.71%). The per-protocol (PP) analysis, excluding patients who dropped-out before collecting their final result, showed that 58/59 (98.31% (CI: 91-99.7%)) of patients in the reference group and 59/59 (100% (CI: 93.89-100%) of the test group achieved SVR12. Non-inferiority was declared since the upper bound of the two-sided 95% CI for the difference in proportions of SVR12 between groups (P(reference)-P(test)) did not exceed the specified non-inferiority margin of +0.1 (10%), both in ITT population (-1.67%, CI: -9.8%-+5.9%), and in the PP population (-1.69%, CI: -9%-+4.58%). No fatalities or serious adverse events were reported during the period of the study. Similar rates of non-serious adverse events were reported in both groups with a trend of higher incidence rate in the fixed 12weeks group; all were mild in severity. INTERPRETATION: Shortening the duration of therapy based on observed vRVR could provide a prudent basis to avoid unnecessary long treatment courses. This could not only reduce the drug exposure and the risk of adverse drug reactions, but also cut the cost of full treatment course with such expensive medications by one third. This could economize the treatment budget at the individual out-of-pocket level as well as the public health services and insurance levels and allow for better utilization of public health resources.

Asunto(s)

Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Imidazoles/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Carbamatos , Quimioterapia Combinada , Egipto , Femenino , Humanos , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Pirrolidinas , Sofosbuvir/administración & dosificación , Sofosbuvir/efectos adversos , Resultado del Tratamiento , Valina/análogos & derivados

RESUMEN

BACKGROUND: This is the second and final report for our study designed to compare two generic sofosbuvir products for the degree and speed of virologic response to a dual anti-hepatitis C virus (HCV) treatment protocol. We aimed to test the applicability of the early virus response kinetics and the very rapid virologic response (vRVR) rate as quick outcome measures for accelerated comparative efficacy studies and as a foundation for a personalized response-guided therapy. METHODS: Fifty eligible chronic HCV patients were randomized to either one of two generic sofosbuvir products (Gratisovir or Grateziano) at a daily dose of one 400 mg tablet plus a weight-based ribavirin dose. Data were compared between the groups for early virus response kinetics and vRVR rates in relation to the rates of final sustained virologic response at week 12 posttreatment (SVR12). RESULTS: The Log10 transformed virus load (Log polymerase chain reaction) curves showed fairly similar rapid decline during the first 2 weeks, with no significant difference between the groups at four analysis points throughout the study by repeated-measures factorial analysis of variance test (P=0.48). The SVR12 rates were 96% (95% confidence interval, 79.6%-99.9%) in Gratisovir group (24/25) and 95.7% (95% confidence interval, 78%-99.9%) in Grateziano group (22/23). There was no statistically significant difference found by exact test (P>0.999). There was a significant association between the vRVR and the SVR12, with 100% positive predictive value (38/38 of those who had vRVR, achieved a final SVR12) and 82.6% sensitivity (among the total 46 with SVR12, 38 were having vRVR). CONCLUSION: We can conclude from our study that the early HCV response kinetics and the vRVR rates could be used as sensitive quick markers for efficacy (with a very high positive predictive value for SVR12), based on our accelerated comparative efficacy research model. This might open the way for new models of accelerated equivalence efficacy studies along with the bioequivalence kinetics studies to test a generic drug against a reference. Also, the early response kinetics and the vRVR might be used as qualifiers for a personalized course of treatment. This could shorten unnecessarily long treatment courses in rapid responders and might help to avoid relapses in slow responders.

Asunto(s)

Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Medicina de Precisión , Ribavirina/farmacología , Antivirales/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Ribavirina/administración & dosificación , Relación Estructura-Actividad , Comprimidos , Carga Viral/efectos de los fármacos

RESUMEN

BACKGROUND: We aimed in this interim report to compare two registered generic sofosbuvir products for the degree and speed of virologic response to a dual antiviral treatment protocol within the first 2 weeks of treatment. METHODS: Data collected during the period of this interim report from the first 25 patients randomized to either one of two generic sofosbuvir products (Grateziano or Gratisovir) at a daily dose of one 400 mg tablet plus a weight-based ribavirin dose were analyzed for both the degree and speed of virus load reduction at the end of 1 and 2 weeks from starting treatment. RESULTS: The baseline Log10 transformed virus load (Log polymerase chain reaction) showed a fairly similar marked and significant reduction in both groups by more than 4 and 5 Logs at the end of week 1 and 2 of starting treatment, respectively. The differences between the two treatment groups at both analysis points were not statistically significant (P>0.05) by repeated measures factorial analysis of variance test. The differences in proportions of patients with ultra-rapid virologic response at the end of week 1 and very-rapid virologic response at the end of week 2 in both groups were also not statistically significant (P>0.05). CONCLUSION: We can conclude from this interim report that the two generic products Gratisovir and Grateziano are almost equally fast and efficacious in reducing the hepatitis C virus load in our study setting.

Asunto(s)

Antivirales/uso terapéutico , Medicamentos Genéricos/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Sofosbuvir/uso terapéutico , Adulto , Antivirales/efectos adversos , Investigación sobre la Eficacia Comparativa , Medicamentos Genéricos/efectos adversos , Egipto , Femenino , Hepatitis C Crónica/sangre , Hepatitis C Crónica/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/sangre , Sofosbuvir/efectos adversos , Equivalencia Terapéutica , Factores de Tiempo , Resultado del Tratamiento , Carga Viral

RESUMEN

OBJECTIVE: We aimed to investigate the effect of topical application of a Copper indomethacin (Cu-Indo) gel preparation on monosodium iodoacetate (MIA) induced arthritis of the knee joint of rats and to test our hypothesis that copper complex of indomethacin could be a more potent anti-inflammatory agent than its parent compound. METHODS: After induction of osteoarthritis by the intracapsular injection of 50 µL with 40 mg/mL MIA, we compared the anti-inflammatory efficacy and safety of a topical application of 1% indomethacin gel in a dose of 1 g/kg of the gel (equivalent to 10 mg/kg of the active substance) daily for 3 weeks versus three decremental dose levels of Cu-Indo gel: an equivalent dose, half the dose, and 25% of the dose of indomethacin. Anti-inflammatory efficacy was assessed in all treated groups by measurement of serum inflammatory cytokines: interleukin 6, interleukin 8, and tumor necrosis factor alpha; and by the weekly assessment of knee joint swelling. Joint mobility and motor coordination were also assessed once weekly by the accelerating rotarod apparatus; histopathological examination of affected joints was also performed. Safety of topical application of Cu-Indo (0.25, 0.5, and 1 g/kg) for up to 3 months to rats' skin was determined by the estimation of a complete blood count, liver and kidney functions, and histopathologic examination for target tissues. RESULTS: Cu-Indo gel at lower doses was superior to or at least as effective as its parent substance, indomethacin, in most of the studied parameters of inflammation. The lowest tested dose of Cu-Indo, corresponding to 25% of the parent substance indomethacin, exhibited the highest efficacy in reducing the elevated serum-tested interleukins and in increasing the time of duration on the rotarod test, whereas its effect on reduction of edema and tumor necrosis factor alpha was comparable to that of the others. After 3 months of daily application, there were no notable changes in studied safety parameters with the lowest Cu-Indo dose, but the group treated with the higher dose showed a small but statistically significant increase in serum-unconjugated bilirubin and a slight decrease in hemoglobin levels, red blood cells, and platelet count, with normal indices denoting a slight hemolytic effect at the highest dose. CONCLUSION: Cu-Indo gel has potent anti-inflammatory activity against joint inflammation in the MIA-treated rat model of osteoarthritis at doses of 0.25, 0.5, and 1 g/kg. The lowest studied dose was better on both safety and efficacy parameters.

Asunto(s)

Antiinflamatorios no Esteroideos/administración & dosificación , Artritis Experimental/tratamiento farmacológico , Cobre/administración & dosificación , Indometacina/administración & dosificación , Indometacina/uso terapéutico , Inflamación/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Experimental/inducido químicamente , Cobre/química , Cobre/uso terapéutico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Geles/administración & dosificación , Geles/química , Geles/uso terapéutico , Indometacina/química , Ácido Yodoacético , Masculino , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/química , Compuestos Organometálicos/uso terapéutico , Osteoartritis/inducido químicamente , Ratas , Ratas Wistar

RESUMEN

BACKGROUND: Development of an optimal interferon-free regimen for chronic hepatitis C virus infection is believed to require the combination of different drug classes to provide good antiviral efficacy, clinical and quality of life benefits, as well as a high barrier to resistance. Viron(®) is a new herbal drug in film-coated tablet form, and is based on a mixture of herbs with known hepatoprotective and antiviral properties. We conducted this study to explore the safety and the potential clinical and quality of life benefits of this product in patients with chronic hepatitis C infection. METHODS: Eighty-two consecutive patients presenting to our outpatient clinics as already-known or newly-diagnosed cases of chronic hepatitis C virus (HCV) infection, were entered into the study and randomized to three groups to receive escalating doses of Viron for 6 months. Virological, clinical, and enzyme responses, as well as quality of life index scores for chronic liver disease were compared between the groups. RESULTS: Of the 20 patients treated with the highest dose of Viron (three tablets twice daily), two (10%) had a complete virological response at the end of treatment (ETR) and two (10%) had a partial ETR, defined as a decrease in viral load of at least 2-log10 at the end of 6 months of treatment, whereas patients treated with the medium dose (two tablets twice daily) and the lowest dose (one tablet twice daily) showed a significantly lower ETR (P=0.043). Alanine aminotransferase levels and scores on the Chronic Liver Disease Questionnaire improved to a significantly greater extent in the highest dose group (P=0.007 and P=0.021, respectively). No serious adverse effects attributable to the herbal formulation were reported in any of the groups, apart from mild transient nausea, bloating, giddiness, and headache in two patients in the group receiving two tablets twice daily and in three patients in the group receiving three tablets twice daily. CONCLUSION: We conclude that this herbal formulation is potentially safe and may offer some added clinical and quality of life benefits when used in the treatment of patients with chronic hepatitis C virus infection. Larger studies could be warranted to evaluate the effects of using this formulation as an add-on therapy to an all-oral combination of a directly acting antiviral drug protocol in the treatment of chronic hepatitis C.

Asunto(s)

Antivirales/efectos adversos , Antivirales/uso terapéutico , Productos Biológicos/efectos adversos , Productos Biológicos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Adolescente , Adulto , Antivirales/administración & dosificación , Productos Biológicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Comprimidos , Adulto Joven

RESUMEN

BACKGROUND: Renal colic is typically characterized by the sudden onset of severe pain radiating from the flank to the groin and its acute management in emergency departments essentially aims at rapid pain relief. Spasmofen(®) is a brand of Amriya Pharmaceutical Industries in the form of rectal suppositories containing ketoprofen 100 mg and hyoscine butylbromide 10 mg. This combination is intended for the rapid relief of severe colicky pain in the renal system, hepatobiliary system, or gastrointestinal tract. This trial aims to compare a single-dose of Spasmofen rectal suppository to a single intravenous (IV) ketorolac tromethamine 30 mg/2 mL dose in patients with acute renal colic. METHODS: A total of 80 eligible consecutive patients presenting to the emergency departments of two medical centers with acute renal colic were included in the study. Eligible patients who signed the informed consent were randomly assigned into two treatment groups: an experimental group (Spasmofen group) who received one Spasmofen rectal suppository plus an IV injection of 2 mL of normal saline solution; and a control group (ketorolac group) who received one ketorolac 30 mg/2 mL ampoule IV plus one placebo suppository. Treatment success, defined as a change in the verbal rating score from severe or moderate pain to none or mild at 60 minutes after the dose, was compared between groups using the chi-square/Fisher's exact test. Percentage reductions in visual pain analog scale (VPAS) scores at 15 and 60 minutes after the dose were compared between groups using the Z-test for proportions. RESULTS: Successful treatment at 60 minutes occurred in 35 of 40 (87.5%) of Spasmofen-treated patients and in 33 of 40 (82.5%) of ketorolac-treated patients. The difference was not statistically significant by Fisher's exact test (P=0.755). The mean percentage reduction of VPAS after 15 minutes was 61.82% in the Spasmofen-treated group and 64.76% in the ketorolac-treated group. The difference was also not statistically significant by the Z-test for proportions (P=0.795). Sixty minutes after being treated, Spasmofen was associated with a statistically significant greater reduction in VPAS (mean% reduction =92.36%) than ketorolac (75.06%; P=0.0466). CONCLUSION: Single-dose Spasmofen rectal suppository might be a safe and effective first-aid treatment for the emergency department relief of acute renal colic.

Asunto(s)

Codeína/administración & dosificación , Morfina/administración & dosificación , Noscapina/administración & dosificación , Papaverina/administración & dosificación , Cólico Renal/tratamiento farmacológico , Derivados de Escopolamina/administración & dosificación , Administración Rectal , Adulto , Codeína/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Tratamiento de Urgencia , Femenino , Humanos , Ketorolaco/administración & dosificación , Masculino , Persona de Mediana Edad , Morfina/efectos adversos , Noscapina/efectos adversos , Dimensión del Dolor , Papaverina/efectos adversos , Derivados de Escopolamina/efectos adversos

RESUMEN

BACKGROUND: Mild cognitive impairment encompasses the clinical continuum between physiologic age-related cognitive changes and dementia. A variety of medications, including herbal preparations (in particular Ginkgo biloba and Panax ginseng), have been advocated as treatments for cognitive impairment in the elderly. In this study, we investigated the effect of an already marketed dietary supplement (Memo®) combining 750 mg of lyophilized royal jelly with standardized extracts of G. biloba 120 mg and P. ginseng 150 mg on Mini-Mental State Examination (MMSE) scores in patients with mild cognitive impairment. METHODS: Sixty-six subjects presenting with forgetfulness and satisfying the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) clinical criteria for mild cognitive impairment were randomly divided into an experimental group treated with one Memo capsule before breakfast daily for 4 weeks and a control group who took placebo. The mean change in MMSE score from baseline and reported adverse effects were compared between the two groups. RESULTS: The mean change in MMSE score in the group treated with Memo for 4 weeks was significantly greater than in the control group (+2.07 versus +0.13, respectively) by the Student's t-test (t = 6.485, P < 0.0001). This was also true after adjusting for age as a covariate and educational level as a factor nested within the treatment groups in a general linear model (analysis of covariance, F = 9.675 [corrected model], P < 0.0001). CONCLUSION: This combined triple formula may be beneficial in treating the cognitive decline that occurs during the aging process as well as in the early phases of pathologic cognitive impairment typical of insidious-onset vascular dementia and in the early stages of Alzheimer's disease. Larger-sized studies with longer treatment durations are needed to confirm this.

Asunto(s)

Disfunción Cognitiva/tratamiento farmacológico , Ácidos Grasos/uso terapéutico , Ginkgo biloba , Panax , Fitoterapia , Anciano , Anciano de 80 o más Años , Envejecimiento , Suplementos Dietéticos , Combinación de Medicamentos , Egipto , Femenino , Liofilización , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Resultado del Tratamiento

RESUMEN

The practice of conventional medicine has markedly changed since the introduction of the concept of the evidence-based medicine. Randomized controlled study design and large sample size were the only justifications for level A or B evidence at the summit of what is called the evidence pyramid. A lot of medical interventions that were based on a plethora of basic researches and multiple large real world or observational studies in humans became questioned now by the results of even a single large sized randomized controlled trial (RCT). The conflicting evidences for the value of vitamin E and Omega-3 fatty acids in cardiovascular diseases are famous examples for such perplexity. This article discusses this problem on the basis of scientific, ethical, and statistical critical appraisal. To conclude, in this era of overwhelming flow of data, it should be emphasized in short, fast-to-read articles that it is important to consider not only the level of evidence "as dictated by the study design and sample size" but also the relevance of evidence. Studies tell us about populations but we treat individuals. The type of the studied individuals, the enrollment criteria, the methodology, the dose of the studied drug and all the combined medications in the study should be clearly considered whenever the reported results are to be generalized beyond the specific situation studied. Comparing the effect of an active drug against placebo by giving either one of them to a group already treated with other multiple drugs (optimum medical therapy) could be a misleading indicator for the pure efficacy of the active drug. Many confounding variables such as known "or unknown" drug-drug interactions, sharing mechanisms of action or unexpected adverse drug reactions can afflict only the group randomized to take the active drug. These variables will not affect the control group simply because they add to their optimized multiple drug therapy an inert placebo.