Recommendations for the use of ultrasound in rheumatoid arthritis: literature review and SONAR score experience

Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed.

A history and overview of phenotypic variability in CYP2D6 activity

CYP2D6 is a human cytochrome P450 that is responsible for the metabolism of a large number of drugs and chemicals. Interest in CYP2D6 has largely centered on the wide interindividual variability in its catalytic activity that stems from a common genetic polymorphism in the CYP2D6 gene. Two major phenotypes exist, extensive metabolizer (EM) and poor metabolizer (PM), together with the two less studied phenotypes of ultrarapid metabolizer (UM) and intermediate metabolizer. These phenotypes are the expression of an underlying allelomorphism in CYP2D6 and are also context dependent. Several drugs that are CYP2D6 substrates display polymorphic metabolism, that is, the existence in the population of multiple phenotypes, in particular EM and PM. The most notable drugs in this regard are debrisoquine and sparteine, although there are also data for a few others, in particular, dextromethorphan and metoprolol. Many nongenetic factors can alter the expression of CYP2D6 phenotypes, the most significant of which is the presence of other drugs. In this context, the EM phenotype may not be immutable, with potential conversion into a PM phenocopy, due to significantly impaired CYP2D6 metabolism in the presence of other CYP2D6 substrates and inhibitors. This phenotype interconversion generated great concern and helped drive the movement away from phenotyping based upon drug administration to genotyping of acquired DNA samples. However, ascertaining the presence of CYP2D6 alleles in a DNA sample does not determine the metabolism and pharmacokinetics of CYP2D6 substrates in that subject: it is a forecast, much like the weather forecast and, as we all know regarding the weather, the forecast can be inaccurate at times.

TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES: A Literature Review and Consensus Recommendations

PURPOSE A review of treat-and-extend regimens (TERs) with intravitreal anti-vascular endothelial growth factor agents in retinal diseases. METHODS There is a lack of consensus on the definition and optimal application of TER in clinical practice. This article describes the supporting evidence and subsequent development of a generic algorithm for TER dosing with anti-vascular endothelial growth factor agents, considering factors such as criteria for extension. RESULTS A TER algorithm was developed; TER is defined as an individualized proactive dosing regimen usually initiated by monthly injections until a maximal clinical response is observed (frequently determined by optical coherence tomography), followed by increasing intervals between injections (and evaluations) depending on disease activity. The TER regimen has emerged as an effective approach to tailoring the dosing regimen and for reducing treatment burden (visits and injections) compared with fixed monthly dosing or monthly visits with optical coherence tomography-guided regimens (as-needed or pro re nata). It is also considered a suitable approach in many retinal diseases managed with intravitreal anti-vascular endothelial growth factor therapy, given that all eyes differ in the need for repeat injections. CONCLUSION It is hoped that this practical review and TER algorithm will be of benefit to health care professionals interested in the management of retinal diseases.

From Connecting Hindus to Uniting Global Hinduism: History and Guiding Principles of Hinduism Today

Hinduism Today is a quarterly magazine that appears in roughly 15.000 copies, shipped to nearly 60 countries worldwide. The majority of readers are Hindus in diverse diaspora countries, mainly Singapur, Malaysia, Mauritius, Trinidad und the USA. Its editors are monks of Kauai Adheenam, belonging to the Śaiva Siddhānta Church, situated in Kauai, Hawai’i, USA. One of the magazine’s declared goals is to foster global Hindu solidarity and educate Hindus worldwide about their religion. In this paper, I want to take a look at the history of this magazine in connection with the Śaiva Siddhānta Church, and at the development of the expressed aims behind its publication. For this, I draw on fieldwork done in Kauai in January, 2014. After a brief introduction to some theoretical and methodological preliminaries of my work, I shall, give an overview of the history of the Śaiva Siddhānta Church, founded by Satguru Sivaya Subramuniyaswami. Following this, I will deal in more detail with the origins and development of the magazine and the websites connected with it. I will focus especially on the role the magazine was intended to play for global Hindu diasporas. A fourth chapter will analyze the modes of definition employed in order to depict Hinduism as a unified global religion. In conclusion, I shall briefly reflect upon the specific agenda of “Global Hinduism” and the strategies of positioning as followed by the publishers of Hinduism Today.

Psychological adaptation to spousal bereavement in old age. The role of trait resilience, marital history, and context of death

This research examined the effect of marital status and gender on various indicators of psychological adaptation, namely depressive symptoms, loneliness, and life satisfaction. It further explores the role of trait resilience, marital history, and context of death for predicting These outcomes in bereaved individuals. Four hundred eighty widowed individuals aged between 60 and 89 were compared with 759 married peers. Main effects were found for marital status and gender for all indicators. The regression analyses illustrate the multifaceted structure of psychological adaptation. Trait resilience is a key factor in adapting to spousal bereavement, whereas marital history and the context are secondary.

Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.

Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Late-glacial and Holocene vegetation history and dynamics as shown by pollen and plant macrofossil analyses in annually laminated sediments from Soppensee, central Switzerland

The palynostratigraphy of two sediment cores from Soppensee, Central Switzerland (596 m asl) was correlated with nine regional pollen assemblage zones defined for the Swiss Plateau. This biostratigraphy shows that the sedimentary record of Soppensee includes the last 15 000 years, i.e. the entire Late-glacial and Holocene environmental history. The vegetation history of the Soppensee catchment was inferred by pollen and plant-macrofossil analyses on three different cores taken in the deepest part of the lake basin (27 m). On the basis of a high-resolution varve and calibrated radiocarbonchronology it was possible to estimate pollen accumulation rates, which together with the pollen percentage data, formed the basis for the interpretation of the past vegetation dynamics. The basal sediment dates back to the last glacial. After reforestation with juniper and birch at ca. 12 700 B.P., the vegetation changed at around 12 000 B.P. to a pine-birch woodland and at the onset of the Holocene to a mixed deciduous forest. At ca. 7000 B.P., fir expanded and dominated the vegetation with beech becoming predominant at ca. 50014C-years later until sometime during the Iron Age. Large-scale deforestation, especially during the Middle Ages, altered the vegetation cover drastically. During the Late-glacial period two distinct regressive phases in vegetation development are demonstrated, namely, the Aegelsee oscillation (equivalent to the Older Dryas biozone) and the Younger Dryas biozone. No unambiguous evidence for Holocene climatic change was detected at Soppensee. Human presence is indicated by early cereal pollen and distinct pulses of forest clearance as a result of human activity can be observed from the Neolithic period onwards.