An Overview of the Evidence and Mechanisms of Herb–Drug Interactions

Despite the lack of sufficient information on the safety of herbal products, their use as alternative and/or complementary medicine is globally popular. There is also an increasing interest in medicinal herbs as precursor for pharmacological actives. Of serious concern is the concurrent consumption of herbal products and conventional drugs. Herb–drug interaction (HDI) is the single most important clinical consequence of this practice. Using a structured assessment procedure, the evidence of HDI presents with varying degree of clinical significance. While the potential for HDI for a number of herbal products is inferred from non-human studies, certain HDIs are well established through human studies and documented case reports. Various mechanisms of pharmacokinetic HDI have been identified and include the alteration in the gastrointestinal functions with consequent effects on drug absorption; induction and inhibition of metabolic enzymes and transport proteins; and alteration of renal excretion of drugs and their metabolites. Due to the intrinsic pharmacologic properties of phytochemicals, pharmacodynamic HDIs are also known to occur. The effects could be synergistic, additive, and/or antagonistic. Poor reporting on the part of patients and the inability to promptly identify HDI by health providers are identified as major factors limiting the extensive compilation of clinically relevant HDIs. A general overview and the significance of pharmacokinetic and pharmacodynamic HDI are provided, detailing basic mechanism, and nature of evidence available. An increased level of awareness of HDI is necessary among health professionals and drug discovery scientists. With the increasing number of plant-sourced pharmacological actives, the potential for HDI should always be assessed in the non-clinical safety assessment phase of drug development process. More clinically relevant research is also required in this area as current information on HDI is insufficient for clinical applications

Twice-daily versus once-daily antiretroviral therapy and coformulation strategies in HIV-infected adults: benefits, risks, or burden?

The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices

Medicines development and regulation in Africa

Africa is one of the world’s fastest-growing economic regions, with a rise in its pharmaceutical industry value from $4.7 billion in 2003 to$20.8 billion in 2013. Multinational pharmaceutical companies are becoming more active in drug production and clinical trials across Africa, and there is an increase in the number of local companies engaged in medicines development and marketing. Such expansion of the local pharmaceutical industry requires trained pharmaceutical specialists to support it. The current situation and future requirements for local medicines development, regulation, education and training needs are discussed

Health-related quality of life and its association with medication adherence in active pulmonary tuberculosis– a systematic review of global literature with focus on South Africa

IntroductionTuberculosis (TB) is a leading cause of morbidity and mortality in South Africa. Clinical parameters are important objective outcomes in TB; however they often are not directly correlated with subjective well-being of the patient, but can be assessed using patient-reported outcome (PRO) measures. Health-related quality of life (HRQOL) is a specific PRO generally multi-dimensional in nature and includes physical, mental and social health domains. The inclusion of HRQOL PROs in trials and clinical practice can provide additional information beyondclinical and microbiological parameters. Furthermore, HRQOL may be associated with medication adherence. This review focuses on patient-reported HRQOL and its association with medication adherence in TB patients in South Africa.MethodsA comprehensive search strategy was developed focusing on the impact of TB on patient-reported HRQOL,the existence of a conceptual framework of TB-specific HRQOL, determinants of medication adherence and the association of HRQOL with medication adherence. Data were extracted from all identified articles and additionaldata extraction was performed by two independent reviewers with special focus on longitudinal studies in order to understand changes of HRQOL and adherence over time. Research gaps were identified with regard to patient-reported HRQOL and medication adherence.ResultsA total of 66 articles met the eligibility criteria. Ten HRQOL studies and one adherence study used a longitudinal design, none of these in South Africa. A variety of different generic and disease-specific HRQOL measures were identified in the articles. In South Africa four HRQOL and five adherence studies (non-longitudinal) were published. Similar factors (socio-demographic, socio-economic, disease-related, therapy-related and psycho-social aspects) affect HRQOL and adherence. Although standard TB treatment improved all health domains, psychological well-being and social functioning remained impaired in microbiologically cured patients after treatment.ConclusionWhile evidence of TB impact on HRQOL and medication adherence and their association exists, it is verylimited for the South African situation. No valid and reliable TB-specific HRQOL measures were identified in this systematicreview. An assessment of HRQOL in TB patients in South Africa is required as this may assist with improving current disease management programmes, medication adherence and national treatment guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-016-0442-6) contains supplementary material, which is available to authorized users

Three-Dimensional Software- and MR-Imaging-Based Muscle Volumetry Reveals Overestimation of Supraspinatus Muscle Atrophy Using Occupation Ratios in Full-Thickness Tendon Tears

Supraspinatus muscle atrophy is widely determined from oblique-sagittal MRI by calculating the occupation ratio. This ex vivo and clinical study aimed to validate the accuracy of 3D software- and MR-imaging-based muscle volumetry, as well as to assess the influence of the tear pattern on the occupation ratio. Ten porcine muscle specimens were volumetrized using the physical water displacement volumetry as a standard of reference. A total of 149 individuals with intact supraspinatus tendons, partial tears, and full-thickness tears had 3T MRI. Two radiologists independently determined occupation ratio values. An excellent correlation with a Pearson's r of 0.95 for the variables physical volumetry using the water displacement method and MR-imaging-based muscle volumetry using the software was found and formed the standard of reference for the patient study. The inter-reader reliability was 0.92 for occupation ratios. The correlation between occupation ratios and software-based muscle volumes was good in patients with intact tendons (0.84) and partial tears (0.93) but considerably lower in patients with full-thickness tears (0.68). Three-dimensional-software- and MR-imaging-based muscle volumetry is reliable and accurate. Compared to 3D muscle volumetry, the occupation ratio method overestimates supraspinatus muscle atrophy in full-thickness tears, which is most likely due to the medial retraction of the myotendinous unit

Barriers to adherence to antiretroviral treatment in a regional hospital in Vredenburg, Western Cape, South Africa

BACKGROUND: South Africa currently runs the largest public antiretroviral treatment (ART) programme in the world, with over 80% of people living with HIV and/or AIDS on ART. However, in order to appreciate the benefits of using ART, patients are subject to uncompromising and long-term commitments of taking at least 95% of their treatment as prescribed. Evidence shows that this level of adherence is seldom achieved because of a multilevel and sometimes interwoven myriad of factors. Objective: We described the challenges faced by patients on ART in Vredenburg with regard to ART adherence. METHODS: A descriptive qualitative research design was used. Eighteen non-adhering patients on ART in the Vredenburg regional hospital were purposefully selected. Using a semistructured interview guide, we conducted in-depth interviews with the study participants in their mother tongue (Afrikaans). The interviews were audio-taped, transcribed verbatim and translated into English. The data were analysed manually using the thematic content analysis method. RESULTS: Stigma, disclosure, unemployment, lack of transport, insufficient feeding, disability grants and alternative forms of therapy were identified as major barriers to adherence, whereas inadequate follow-ups and lack of patient confidentiality came under major criticisms from the patients. CONCLUSION: Interventions to address poverty, stigma, discrimination and disclosure should be integrated with group-based ART adherence models in Vredenburg while further quantitative investigations should be carried out to quantify the extent to which these factors impede adherence in the community.IS

Using internal strain and mass to modulate Dy⋯Dy coupling and relaxation of magnetization in heterobimetallic metallofullerenes DyM2N@C80 and Dy2MN@C80 (M = Sc, Y, La, Lu)

Endohedral clusters inside metallofullerenes experience considerable inner strain when the size of the hosting cage is comparably small. This strain can be tuned in mixed-metal metallofullerenes by combining metals of different sizes. Here we demonstrate that the internal strain and mass can be used as variables to control Dy⋯Dy coupling and relaxation of magnetization in Dy-metallofullerenes. Mixed-metal nitride clusterfullerenes DyxY3−xN@Ih-C80 (x = 0-3) and Dy2LaN@Ih-C80 combining Dy with diamagnetic rare-earth elements, Y and La, were synthesized and characterized by single-crystal X-ray diffraction, SQUID magnetometry, ab initio calculations, and spectroscopic techniques. DyxY3−xN clusters showed a planar structure, but the slightly larger size of Dy3+ in comparison with that of Y3+ resulted in increased elongation of the nitrogen thermal ellipsoid, showing enhancement of the out-of-plane vibrational amplitude. When Dy was combined with larger La, the Dy2LaN cluster appeared strongly pyramidal with the distance between two nitrogen sites of 1.15(1) Å, whereas DyLa2N@C80 could not be obtained in a separable yield. Magnetic studies revealed that the relaxation of magnetization and blocking temperature of magnetization in the DyM2N@C80 series (M = Sc, Y, Lu) correlated with the mass of M, with DySc2N@C80 showing the fastest and DyLu2N@C80 the slowest relaxation. Ab initio calculations predicted very similar g-tensors for Dy3+ ground state pseudospin in all studied DyM2N@C80 molecules, suggesting that the variation in relaxation is caused by different vibrational spectra of these compounds. In the Dy2MN@C80 series (M = Sc, Y, La, Lu), the magnetic and hysteretic behavior was found to correlate with Dy⋯Dy coupling, which in turn appears to depend on the size of M3+. Across the Dy2MN@C80 series, the energy difference between ferromagnetic and antiferromagnetic states changes from 5.6 cm−1 in Dy2ScN@C80 to 3.0 cm−1 in Dy2LuN@C80, 1.0 cm−1 in Dy2YN@C80, and −0.8 cm−1 in Dy2LaN@C80. The coupling of Dy ions suppresses the zero-field quantum tunnelling of magnetization but opens new relaxation channels, making the relaxation rate dependent on the coupling strengths. DyY2N@C80 and Dy2YN@C80 were found to be non-luminescent, while the luminescence reported for DyY2N@C80 was caused by traces of Y3N@C80 and Y2ScN@C8

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG