Is new drug prescribing in primary care specialist induced?

<p>Abstract</p> <p>Background</p> <p>Medical specialists are often seen as the first prescribers of new drugs. However, the extent to which specialists influence new drug prescribing in primary care is largely unknown.</p> <p>Methods</p> <p>This study estimates the influence of medical specialists on new drug prescribing in primary care shortly after market introduction. The influence of medical specialists on prescribing of five new drugs was measured in a cohort of 103 GPs, working in 59 practices, over the period 1999 until 2003. The influence of medical specialists on new drug prescribing in primary care was assessed using three outcome measures. Firstly, the proportion of patients receiving their first prescription for a new or reference drug from a specialist. Secondly, the proportion of GPs prescribing new drugs before any specialist prescribes to their patients. Thirdly, we compared the time until the GP's first own prescribing between GPs who waited for prescriptions from specialists and those who did not.</p> <p>Results</p> <p>The influence of specialists showed considerable differences among the new drugs studied. The proportion of patients receiving their first prescription from a specialist was greatest for the combination salmeterol/fluticasone (60.2%), and lowest for rofecoxib (23.0%). The proportion of GPs prescribing new drugs before waiting for prescriptions from medical specialists ranged from 21.1% in the case of esomeprazole to 32.9% for rofecoxib. Prescribing new drugs by specialists did not shorten the GP's own time to prescribing.</p> <p>Conclusion</p> <p>This study shows that the influence of medical specialists is clearly visible for all new drugs and often greater than for the existing older drugs, but the rapid uptake of new drugs in primary care does not seem specialist induced in all cases. GPs are responsible for a substantial amount of all early prescriptions for new drugs and for a subpopulation specialist endorsement is not a requisite to initiate in new drug prescribing. This contradicts with the idea that the diffusion of newly marketed drugs always follows a two-step model, with medical specialists as the innovators and GPs as the followers.</p

Novel Structural Components of the Ventral Disc and Lateral Crest in Giardia intestinalis

Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP) with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment

Ocean acidification reduces demersal zooplankton that reside in tropical coral reefs

The in situ effects of ocean acidification on zooplankton communities remain largely unexplored. Using natural volcanic CO2 seep sites around tropical coral communities, we show a threefold reduction in the biomass of demersal zooplankton in high-CO2 sites compared with sites with ambient CO2. Differences were consistent across two reefs and three expeditions. Abundances were reduced in most taxonomic groups. There were no regime shifts in zooplankton community composition and no differences in fatty acid composition between CO2 levels, suggesting that ocean acidification affects the food quantity but not the quality for nocturnal plankton feeders. Emergence trap data show that the observed reduction in demersal plankton may be partly attributable to altered habitat. Ocean acidification changes coral community composition from branching to massive bouldering coral species, and our data suggest that bouldering corals represent inferior daytime shelter for demersal zooplankton. Since zooplankton represent a major source of nutrients for corals, fish and other planktivores, this ecological feedback may represent an additional mechanism of how coral reefs will be affected by ocean acidification

Shellfish Face Uncertain Future in High CO2 World: Influence of Acidification on Oyster Larvae Calcification and Growth in Estuaries

BACKGROUND: Human activities have increased atmospheric concentrations of carbon dioxide by 36% during the past 200 years. One third of all anthropogenic CO(2) has been absorbed by the oceans, reducing pH by about 0.1 of a unit and significantly altering their carbonate chemistry. There is widespread concern that these changes are altering marine habitats severely, but little or no attention has been given to the biota of estuarine and coastal settings, ecosystems that are less pH buffered because of naturally reduced alkalinity. METHODOLOGY/PRINCIPAL FINDINGS: To address CO(2)-induced changes to estuarine calcification, veliger larvae of two oyster species, the Eastern oyster (Crassostrea virginica), and the Suminoe oyster (Crassostrea ariakensis) were grown in estuarine water under four pCO(2) regimes, 280, 380, 560 and 800 microatm, to simulate atmospheric conditions in the pre-industrial era, present, and projected future concentrations in 50 and 100 years respectively. CO(2) manipulations were made using an automated negative feedback control system that allowed continuous and precise control over the pCO(2) in experimental aquaria. Larval growth was measured using image analysis, and calcification was measured by chemical analysis of calcium in their shells. C. virginica experienced a 16% decrease in shell area and a 42% reduction in calcium content when pre-industrial and end of 21(st) century pCO(2) treatments were compared. C. ariakensis showed no change to either growth or calcification. Both species demonstrated net calcification and growth, even when aragonite was undersaturated, a result that runs counter to previous expectations for invertebrate larvae that produce aragonite shells. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that temperate estuarine and coastal ecosystems are vulnerable to the expected changes in water chemistry due to elevated atmospheric CO(2) and that biological responses to acidification, especially calcifying biota, will be species-specific and therefore much more variable and complex than reported previously

A short-term in situ CO2 enrichment experiment on Heron Island (GBR)

Ocean acidification poses multiple challenges for coral reefs on molecular to ecological scales, yet previous experimental studies of the impact of projected CO2 concentrations have mostly been done in aquarium systems with corals removed from their natural ecosystem and placed under artificial light and seawater conditions. The Coral–Proto Free Ocean Carbon Enrichment System (CP-FOCE) uses a network of sensors to monitor conditions within each flume and maintain experimental pH as an offset from environmental pH using feedback control on the injection of low pH seawater. Carbonate chemistry conditions maintained in the −0.06 and −0.22 pH offset treatments were significantly different than environmental conditions. The results from this short-term experiment suggest that the CP-FOCE is an important new experimental system to study in situ impacts of ocean acidification on coral reef ecosystems

High CO2 and Silicate Limitation Synergistically Increase the Toxicity of Pseudo-nitzschia fraudulenta

Anthropogenic CO2 is progressively acidifying the ocean, but the responses of harmful algal bloom species that produce toxins that can bioaccumulate remain virtually unknown. The neurotoxin domoic acid is produced by the globally-distributed diatom genus Pseudo-nitzschia. This toxin is responsible for amnesic shellfish poisoning, which can result in illness or death in humans and regularly causes mass mortalities of marine mammals and birds. Domoic acid production by Pseudo-nitzschia cells is known to be regulated by nutrient availability, but potential interactions with increasing seawater CO2 concentrations are poorly understood. Here we present experiments measuring domoic acid production by acclimatized cultures of Pseudo-nitzschia fraudulenta that demonstrate a strong synergism between projected future CO2 levels (765 ppm) and silicate-limited growth, which greatly increases cellular toxicity relative to growth under modern atmospheric (360 ppm) or pre-industrial (200 ppm) CO2 conditions. Cellular Si∶C ratios decrease with increasing CO2, in a trend opposite to that seen for domoic acid production. The coastal California upwelling system where this species was isolated currently exhibits rapidly increasing levels of anthropogenic acidification, as well as widespread episodic silicate limitation of diatom growth. Our results suggest that the current ecosystem and human health impacts of toxic Pseudo-nitzschia blooms could be greatly exacerbated by future ocean acidification and ‘carbon fertilization’ of the coastal ocean

Extreme variations of pCO2 and pH in a macrophyte meadow of the Baltic Sea in summer: evidence of the effect of photosynthesis and local upwelling

The impact of ocean acidification on benthic habitats is a major preoccupation of the scientific community. However, the natural variability of pCO2 and pH in those habitats remains understudied, especially in temperate areas. In this study we investigated temporal variations of the carbonate system in nearshore macrophyte meadows of the western Baltic Sea. These are key benthic ecosystems, providing spawning and nursery areas as well as food to numerous commercially important species. In situ pCO2, pH (total scale), salinity and PAR irradiance were measured with a continuous recording sensor package dropped in a shallow macrophyte meadow (Eckernförde bay, western Baltic Sea) during three different weeks in July (pCO2 and PAR only), August and September 2011.The mean (± SD) pCO2 in July was 383±117 µatm. The mean (± SD) pCO2 and pHtot in August were 239±20 µatm and 8.22±0.1, respectively. The mean (± SD) pCO2 and pHtot in September were 1082±711 µatm and 7.83±0.40, respectively. Daily variations of pCO2 due to photosynthesis and respiration (difference between daily maximum and minimum) were of the same order of magnitude: 281±88 µatm, 219±89 μatm and 1488±574 µatm in July, August and September respectively. The observed variations of pCO2 were explained through a statistical model considering wind direction and speed together with PAR irradiance. At a time scale of days to weeks, local upwelling of elevated pCO2 water masses with offshore winds drives the variation. Within days, primary production is responsible. The results demonstrate the high variability of the carbonate system in nearshore macrophyte meadows depending on meteorology and biological activities. We highlight the need to incorporate these variations in future pCO2 scenarios and experimental designs for nearshore habitats

Decrease in coccolithophore calcification and CO2 since the middle Miocene

International audienceMarine algae are instrumental in carbon cycling and atmospheric carbon dioxide (CO2) regulation. One group, coccolithophores, uses carbon to photosynthesize and to calcify, covering their cells with chalk platelets (coccoliths). How ocean acidification influences coccolithophore calcification is strongly debated, and the effects of carbonate chemistry changes in the geological past are poorly understood. This paper relates degree of coccolith calcification to cellular calcification, and presents the first records of size-normalized coccolith thickness spanning the last 14 Myr from tropical oceans. Degree of calcification was highest in the low-pH, high-CO2 Miocene ocean, but decreased significantly between 6 and 4 Myr ago. Based on this and concurrent trends in a new alkenone εp record, we propose that decreasing CO2 partly drove the observed trend via reduced cellular bicarbonate allocation to calcification. This trend reversed in the late Pleistocene despite low CO2, suggesting an additional regulator of calcification such as alkalinity

The Mutational Spectrum in a Cohort of Charcot-Marie-Tooth Disease Type 2 among the Han Chinese in Taiwan

BACKGROUND: Charcot-Marie-Tooth disease type 2 (CMT2) is a clinically and genetically heterogeneous group of inherited axonal neuropathies. The aim of this study was to extensively investigate the mutational spectrum of CMT2 in a cohort of patients of Han Chinese. METHODOLOGY AND PRINCIPAL FINDINGS: Genomic DNA from 36 unrelated Taiwanese CMT2 patients of Han Chinese descent was screened for mutations in the coding regions of the MFN2, RAB7, TRPV4, GARS, NEFL, HSPB1, MPZ, GDAP1, HSPB8, DNM2, AARS and YARS genes. Ten disparate mutations were identified in 14 patients (38.9% of the cohort), including p.N71Y in AARS (2.8%), p.T164A in HSPB1 (2.8%), and p.[H256R]+[R282H] in GDAP1 (2.8%) in one patient each, three NEFL mutations in six patients (16.7%) and four MFN2 mutations in five patients (13.9%). The following six mutations were novel: the individual AARS, HSPB1 and GDAP1 mutations and c.475-1G>T, p.L233V and p.E744M mutations in MFN2. An in vitro splicing assay revealed that the MFN2 c.475-1G>T mutation causes a 4 amino acid deletion (p.T159_Q162del). Despite an extensive survey, the genetic causes of CMT2 remained elusive in the remaining 22 CMT2 patients (61.1%). CONCLUSIONS AND SIGNIFICANCE: This study illustrates the spectrum of CMT2 mutations in a Taiwanese CMT2 cohort and expands the number of CMT2-associated mutations. The relevance of the AARS and HSPB1 mutations in the pathogenesis of CMT2 is further highlighted. Moreover, the frequency of the NEFL mutations in this study cohort was unexpectedly high. Genetic testing for NEFL and MFN2 mutations should, therefore, be the first step in the molecular diagnosis of CMT2 in ethnic Chinese