Oxidative status and the response to pegylated-interferon alpha2A plus ribavirin in chronic genotype 4 HCV hepatitis

Oxidative stress may play a pathogenic role in chronic hepatitis C (CHC). The present study examined the oxidative status in plasma of patients with CHC who received pegylated interferon and ribavirin therapy. The following groups were included: (1) sustained virological response (28 patients), (2) null response (26 patients), (3) breakthrough (24 patients), (4) relapse (24 patients), (5) spontaneous cure (23 patients) and (6) twenty five normal subjects as a control group. Markers of oxidative stress including plasma malondialdehyde, nitric oxide, reduced glutathione, total antioxidant capacity and uric acid as well as serum ALT, AST, alkaline phosphatase, total bilirubin, albumin, prothrombin time were studied. The study indicated significant decline in reduced glutathione and total antioxidant capacity and markedly elevated levels of malondialdehyde and nitric oxide in all groups compared with the controls. Null response group had the highest levels of malondialdehyde and nitric oxide. Nitric oxide was significantly higher in those with null response compared with all other groups and with control subjects. Uric acid was significantly higher in spontaneous cure group compared with all other groups and with the controls. We concluded that CHC patients had increased oxidative stress. The oxidative status in plasma of these patients was not changed by antiviral therapy. The study also showed an important contribution of nitric oxide in null response patients. High serum uric acid did not interfere with the response and/or did not predict the response to antiviral therapy

Mineral composition, textures and gold habit of the Hamama mineralizations (Central Eastern Desert of Egypt)

Mineralization in the Hamama area exists mainly as quartz-carbonate veins, extending along the contact between the footwall volcanics (basalt, dacite, and rhyolite) and the hanging wall volcaniclastics (laminated, massive and lapilli tuffs with minor breccia). Also, mineralization was recorded as low mineralized cavity filling dolomitic veins occupying NW-SE faults in the basalt. The principal mineralization is represented by a mineral association - quartz + dolomite + calcite + pyrite + chalcopyrite + sphalerite with varying amounts of barite, cinnabar, and galena. It is suggested that these carbonates are post-tectonic low-temperature hydrothermal solution (exhalations) filling fault zones. The injected mineralized carbonate solution dissolved the silicate minerals along contacts. This fault system was caused by the group of porphyritic rhyolite dykes extending NE-SW. The carbonates then were subjected to digenetic processes after their formation resulted in the formation of some secondary sedimentary textures (for example spherulitic, colloform and cockade textures) and dolomitization. The mineralized carbonates are rich in Zn, Cu, and occasionally Pb and Sb. The cavity filling dolomitic veins within basalt show low concentration of ore minerals. The pyrite was crystallized in four phases; the first phase is well-developed pyrite that was formed from the primary hydrothermal solution. The role of bacterial action is obvious in the formation of a second phase framboidal pyrite. The third phase represented by atoll structures formed by diagenetic reworking of the framboidal pyrite. The last phase of pyrite crystallization appears as fine skeletal grains mostly attached to sericite alteration of altered volcanics. The gold and silver are concentrated mainly in the upper iron cap. Secondary supergene enrichment of gold in the oxidation zone, especially in Hamama western zone, is indicated by the reprecipitation of gold as thin filaments or rounded nano-grains along cracks of the oxidized pyrite or at the periphery of the pyrite relicts

Potential role of biosynthesized silver nanoparticles from Aaronsohnia factorovskyi on Hymenolepis nana in BALB/c mice

ABSTRACT Hymenolepiasis is the most common intestinal tapeworm infection in humans caused by an intestinal cestode, Hymenolepis nana. Praziquantel (PZQ) is the most effective drug among other compounds, however, many cases of drug resistance have been reported. Recent research projects have been focused on finding novel therapeutic agents from medicinal plants. In the present study, Aaronsohnia factorovskyi was used against hymenolepiasis in the forms of plant extract (AF) and biosynthesized nanoparticles (AF-NPs) in comparison to PZQ. The results showed that 100 mg/kg AF and 0.5 mg/kg AF-NPs were the most effective doses at suppressing the fecal egg output by 98.39% and 100%, respectively. After the 10th day of treatment, it was not feasible to detect the presence of H. nana eggs in the fecal sample’s examination in the AF-NPs group. Upon treatment with AF-NPs, there were more improvements in the structure of the intestinal tissue than the effect of AF alone and in comparison, to PZQ. Collectively, results showed that A. factoryviski can be used as an anti-hymenolepiasis treatment with minimum side effects and less cost. Also, it was found that NPs are the most effective way, as it offers a faster recovery rate in comparison to natural plant extract

Learning to prescribe - pharmacists' experiences of supplementary prescribing training in England

Background: The introduction of non-medical prescribing for professions such as pharmacy and nursing in recent years offers additional responsibilities and opportunities but attendant training issues. In the UK and in contrast to some international models, becoming a non-medical prescriber involves the completion of an accredited training course offered by many higher education institutions, where the skills and knowledge necessary for prescribing are learnt. Aims: to explore pharmacists' perceptions and experiences of learning to prescribe on supplementary prescribing (SP) courses, particularly in relation to inter-professional learning, course content and subsequent use of prescribing in practice. Methods: A postal questionnaire survey was sent to all 808 SP registered pharmacists in England in April 2007, exploring demographic, training, prescribing, safety culture and general perceptions of SP. Results: After one follow-up, 411 (51%) of pharmacists responded. 82% agreed SP training was useful, 58% agreed courses provided appropriate knowledge and 62% agreed that the necessary prescribing skills were gained. Clinical examination, consultation skills training and practical experience with doctors were valued highly; pharmacology training and some aspects of course delivery were criticised. Mixed views on inter-professional learning were reported – insights into other professions being valued but knowledge and skills differences considered problematic. 67% believed SP and recent independent prescribing (IP) should be taught together, with more diagnostic training wanted; few pharmacists trained in IP, but many were training or intending to train. There was no association between pharmacists' attitudes towards prescribing training and when they undertook training between 2004 and 2007 but earlier cohorts were more likely to be using supplementary prescribing in practice. Conclusion: Pharmacists appeared to value their SP training and suggested improvements that could inform future courses. The benefits of inter-professional learning, however, may conflict with providing professionspecific training. SP training may be perceived to be an instrumental 'stepping stone' in pharmacists' professional project of gaining full IP status

Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate end points in trials: a scoping review

Objective To synthesize the current literature on the use of surrogate end points, including definitions, acceptability, and limitations of surrogate end points and guidance for their design/reporting, into trial reporting items. Study Design and Setting Literature was identified through searching bibliographic databases (until March 1, 2022) and gray literature sources (until May 27, 2022). Data were thematically analyzed into four categories: (1) definitions, (2) acceptability, (3) limitations and challenges, and (4) guidance, and synthesized into reporting guidance items. Results After screening, 90 documents were included: 79% (n = 71) had data on definitions, 77% (n = 69) on acceptability, 72% (n = 65) on limitations and challenges, and 61% (n = 55) on guidance. Data were synthesized into 17 potential trial reporting items: explicit statements on the use of surrogate end point(s) and justification for their use (items 1–6); methodological considerations, including whether sample size calculations were informed by surrogate validity (items 7–9); reporting of results for composite outcomes containing a surrogate end point (item 10); discussion and interpretation of findings (items 11–14); plans for confirmatory studies, collecting data on the surrogate end point and target outcome, and data sharing (items 15–16); and informing trial participants about using surrogate end points (item 17). Conclusion The review identified and synthesized items on the use of surrogate end points in trials; these will inform the development of the Standard Protocol Items: Recommendations for Interventional Trials–SURROGATE and Consolidated Standards of Reporting Trials–SURROGATE extensions

Conducting Economic Evaluations Alongside Randomised Trials: Current Methodological Issues and Novel Approaches

Trial-based economic evaluations are an important aspect of health technology assessment. The availability of patient-level data coupled with unbiased estimates of clinical outcomes means that randomised controlled trials are effective vehicles for the generation of economic data. However there are methodological challenges to trial-based evaluations, which include the collection of reliable data on resource use and cost, choice of health outcome measure, calculating minimally important differences, dealing with missing data, extrapolating outcomes and costs over time and the analysis of multinational trials. This review focuses on the state of the art of selective elements concerning the design, conduct, analysis and reporting of trial-based economic evaluations. The limitations of existing approaches are detailed and novel methods introduced. The review is internationally relevant but with a focus towards practice in the UK

Common Problems, Common Data Model Solutions: Evidence Generation for Health Technology Assessment

There is growing interest in using observational data to assess the safety, effectiveness, and cost effectiveness of medical technologies, but operational, technical, and methodological challenges limit its more widespread use. Common data models and federated data networks offer a potential solution to many of these problems. The open-source Observational and Medical Outcomes Partnerships (OMOP) common data model standardises the structure, format, and terminologies of otherwise disparate datasets, enabling the execution of common analytical code across a federated data network in which only code and aggregate results are shared. While common data models are increasingly used in regulatory decision making, relatively little attention has been given to their use in health technology assessment (HTA). We show that the common data model has the potential to facilitate access to relevant data, enable multidatabase studies to enhance statistical power and transfer results across populations and settings to meet the needs of local HTA decision makers, and validate findings. The use of open-source and standardised analytics improves transparency and reduces coding errors, thereby increasing confidence in the results. Further engagement from the HTA community is required to inform the appropriate standards for mapping data to the common data model and to design tools that can support evidence generation and decision making

Common Problems, Common Data Model Solutions: Evidence Generation for Health Technology Assessment

There is growing interest in using observational data to assess the safety, effectiveness, and cost effectiveness of medical technologies, but operational, technical, and methodological challenges limit its more widespread use. Common data models and federated data networks offer a potential solution to many of these problems. The open-source Observational and Medical Outcomes Partnerships (OMOP) common data model standardises the structure, format, and terminologies of otherwise disparate datasets, enabling the execution of common analytical code across a federated data network in which only code and aggregate results are shared. While common data models are increasingly used in regulatory decision making, relatively little attention has been given to their use in health technology assessment (HTA). We show that the common data model has the potential to facilitate access to relevant data, enable multidatabase studies to enhance statistical power and transfer results across populations and settings to meet the needs of local HTA decision makers, and validate findings. The use of open-source and standardised analytics improves transparency and reduces coding errors, thereby increasing confidence in the results. Further engagement from the HTA community is required to inform the appropriate standards for mapping data to the common data model and to design tools that can support evidence generation and decision making