Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated ...with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.
Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of general relativity (GR), the geodetic and frame-dragging effects, by means ...of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6601.8±18.3 mas/yr and a frame-dragging drift rate of -37.2±7.2 mas/yr, to be compared with the GR predictions of -6606.1 mas/yr and -39.2 mas/yr, respectively ("mas" is milliarcsecond; 1 mas=4.848×10(-9) rad).
As the novel coronavirus disease (COVID-19) pandemic spreads throughout the United States, evidence is mounting that racial and ethnic minorities and socioeconomically disadvantaged groups are ...bearing a disproportionate burden of illness and death. We conducted a retrospective cohort analysis of COVID-19 patients at Sutter Health, a large integrated health system in northern California, to measure potential disparities. We used Sutter's integrated electronic health record to identify adults with suspected and confirmed COVID-19, and we used multivariable logistic regression to assess risk of hospitalization, adjusting for known risk factors, such as race/ethnicity, sex, age, health, and socioeconomic variables. We analyzed 1,052 confirmed cases of COVID-19 from the period January 1-April 8, 2020. Among our findings, we observed that compared with non-Hispanic white patients, non-Hispanic African American patients had 2.7 times the odds of hospitalization, after adjustment for age, sex, comorbidities, and income. We explore possible explanations for this, including societal factors that either result in barriers to timely access to care or create circumstances in which patients view delaying care as the most sensible option. Our study provides real-world evidence of racial and ethnic disparities in the presentation of COVID-19.
Background
Current clinical guidelines identify several psychological treatments for irritable bowel syndrome (IBS). IBS patients, however, have elevated trauma, life stress, relationship conflicts, ...and emotional avoidance, which few therapies directly target. We tested the effects of emotional awareness and expression training (EAET) compared to an evidence‐based comparison condition—relaxation training—and a waitlist control condition.
Methods
Adults with IBS (N=106; 80% female, Mean age=36 years) were randomized to EAET, relaxation training, or waitlist control. Both EAET and relaxation training were administered in three, weekly, 50‐minute, individual sessions. All patients completed the IBS Symptom Severity Scale (primary outcome), IBS Quality of Life, and Brief Symptom Inventory (anxiety, depressive, and hostility symptoms) at pretreatment and at 2 weeks posttreatment and 10 weeks follow‐up (primary endpoint).
Key Results
Compared to waitlist controls, EAET, but not relaxation training, significantly reduced IBS symptom severity at 10‐week follow‐up. Both EAET and relaxation training improved quality of life at follow‐up. Finally, EAET did not reduce psychological symptoms, whereas relaxation training reduced depressive symptoms at follow‐up (and anxiety symptoms at posttreatment).
Conclusions & Inferences
Brief emotional awareness and expression training that targeted trauma and emotional conflicts reduced somatic symptoms and improved quality of life in patients with IBS. This emotion‐focused approach may be considered an additional treatment option for IBS, although research should compare EAET to a full cognitive‐behavioral protocol and determine which patients are best suited for each approach. Registered at clinicaltrials.gov (NCT01886027).
This randomized controlled trial compared the effects of emotional awareness and expression training with relaxation training, and a waitlist control condition. This study demonstrated that emotional awareness and expression training reduced IBS symptoms and improved quality of life, which points to the value of this novel approach for patients with IBS.
Kinase inhibitors show great promise as a new class of therapeutics. Here we describe an efficient way to determine kinase inhibitor specificity by measuring binding of small molecules to the ATP ...site of kinases. We have profiled 20 kinase inhibitors, including 16 that are approved drugs or in clinical development, against a panel of 119 protein kinases. We find that specificity varies widely and is not strongly correlated with chemical structure or the identity of the intended target. Many novel interactions were identified, including tight binding of the p38 inhibitor BIRB-796 to an imatinib-resistant variant of the ABL kinase, and binding of imatinib to the SRC-family kinase LCK. We also show that mutations in the epidermal growth factor receptor (EGFR) found in gefitinib-responsive patients do not affect the binding affinity of gefitinib or erlotinib. Our results represent a systematic small molecule-protein interaction map for clinical compounds across a large number of related proteins.
Objective To quantify the change in prescribing of antibiotic prophylaxis before invasive dental procedures for patients at risk of infective endocarditis, and any concurrent change in the incidence ...of infective endocarditis, following introduction of a clinical guideline from the National Institute for Health and Clinical Excellence (NICE) in March 2008 recommending the cessation of antibiotic prophylaxis in the United Kingdom.Design Before and after study.Setting England.Population All patients admitted to hospital in England with a primary or secondary discharge diagnosis of acute or subacute infective endocarditis.Main outcome measures Monthly number of prescriptions for antibiotic prophylaxis consisting of a single 3 g oral dose of amoxicillin or a single 600 mg oral dose of clindamycin, and monthly number of cases of infective endocarditis, infective endocarditis related deaths in hospital, or cases of infective endocarditis with a possible oral origin for streptococci.Results After the introduction of the NICE guideline there was a highly significant 78.6% reduction (P<0.001) in prescribing of antibiotic prophylaxis, from a mean 10 277 (SD 1068) prescriptions per month to 2292 (SD 176). Evidence that the general upward trend in cases of infective endocarditis before the guideline was significantly altered after the guideline was lacking (P=0.61). Using a non-inferiority test, an increase in the number of cases of 9.3% or more could be excluded after the introduction of the guideline. Similarly an increase in infective endocarditis related deaths in hospital of 12.3% or more could also be excluded.Conclusion Despite a 78.6% reduction in prescribing of antibiotic prophylaxis after the introduction of the NICE guideline, this study excluded any large increase in the incidence of cases of or deaths from infective endocarditis in the two years after the guideline. Although this lends support to the guideline, ongoing data monitoring is needed to confirm this, and further clinical trials should determine if antibiotic prophylaxis still has a role in protecting some patients at particularly high risk.
Recent studies of contaminants under the Canadian Northern Contaminants Program (NCP) have substantially enhanced our understanding of the pathways by which contaminants enter Canada’s Arctic and ...move through terrestrial and marine ecosystems there. Building on a previous review (Barrie et al., Arctic contaminants: sources, occurrence and pathways. Sci Total Environ 1992:1–74), we highlight new knowledge developed under the NCP on the sources, occurrence and pathways of contaminants (organochlorines, Hg, Pb and Cd, PAHs, artificial radionuclides). Starting from the global scale, we examine emission histories and sources for selected contaminants focussing especially on the organochlorines. Physical and chemical properties, transport processes in the environment (e.g. winds, currents, partitioning), and models are then used to identify, understand and illustrate the connection between the contaminant sources in industrial and agricultural regions to the south and the eventual arrival of contaminants in remote regions of the Arctic. Within the Arctic, we examine how contaminants impinge on marine and terrestrial pathways and how they are subsequently either removed to sinks or remain where they can enter the biosphere. As a way to focus this synthesis on key concerns of northern residents, a number of special topics are examined including: a mass balance for HCH and toxaphene (CHBs) in the Arctic Ocean; a comparison of PCB sources within Canada’s Arctic (Dew Line Sites) with PCBs imported through long-range transport; an evaluation of concerns posed by three priority metals — Hg, Pb and Cd; an evaluation of the risks from artificial radionuclides in the ocean; a review of what is known about new-generation pesticides that are replacing the organochlorines; and a comparison of natural vs. anthropogenic sources of PAH in the Arctic. The reseArch and syntheses provide compelling evidence for close connectivity between the global emission of contaminants from industrial and agricultural activities and the Arctic. For semi-volatile compounds that partition strongly into cold water (e.g. HCH) we have seen an inevitable loading of Arctic aquatic reservoirs. Drastic HCH emission reductions have been rapidly followed by reduced atmospheric burdens with the result that the major reservoir and transport agent has become the ocean. In the Arctic, it will take decades for the upper ocean to clear itself of HCH. For compounds that partition strongly onto particles, and for which the soil reservoir is most important (e.g. PCBs), we have seen a delay in their arrival in the Arctic and some fractionation toward more volatile compounds (e.g. lower-chlorinated PCBs). Despite banning the production of PCB in the 1970s, and despite decreases of PCBs in environmental compartments in temperate regions, the Arctic presently shows little evidence of reduced PCB loadings. We anticipate a delay in PCB reductions in the Arctic and environmental lifetimes measured in decades. Although artificial radionuclides have caused great concern due to their direct disposal on Russian Shelves, they are found to pose little threat to Canadian waters and, indeed, much of the radionuclide inventory can be explained as remnant global fallout, which was sharply curtailed in the 1960s, and waste emissions released under license by the European reprocessing plants. Although Cd poses a human dietary concern both for terrestrial and marine mammals, we find little evidence that Cd in marine systems has been impacted by human activities. There is evidence of contaminant Pb in the Arctic, but loadings appear presently to be decreasing due to source controls (e.g. removal of Pb from gasoline) in Europe and North America. Of the metals, Hg provokes the greatest concern; loadings appear to be increasing in the Arctic due to global human activities, but such loadings are not evenly distributed nor are the pathways by which they enter and move within the Arctic well understood.
The Kuiper belt is a collection of small bodies (Kuiper belt objects, KBOs) that lie beyond the orbit of Neptune and which are believed to have formed contemporaneously with the planets. Their small ...size and great distance make them difficult to study. KBO 55636 (2002 TX300) is a member of the water-ice-rich Haumea KBO collisional family. The Haumea family are among the most highly reflective objects in the Solar System. Dynamical calculations indicate that the collision that created KBO 55636 occurred at least 1 Gyr ago. Here we report observations of a multi-chord stellar occultation by KBO 55636, which occurred on 9 October 2009 ut. We find that it has a mean radius of 143 ± 5 km (assuming a circular solution). Allowing for possible elliptical shapes, we find a geometric albedo of in the V photometric band, which establishes that KBO 55636 is smaller than previously thought and that, like its parent body, it is highly reflective. The dynamical age implies either that KBO 55636 has an active resurfacing mechanism, or that fresh water-ice in the outer Solar System can persist for gigayear timescales.
We report here the transcriptional profiling of the cell cycle on a genome-wide scale in human fibroblasts. We identified approximately 700 genes that display transcriptional fluctuation with a ...periodicity consistent with that of the cell cycle. Systematic analysis of these genes revealed functional organization within groups of coregulated transcripts. A diverse set of cytoskeletal reorganization genes exhibit cell-cycle-dependent regulation, indicating that biological pathways are redirected for the execution of cell division. Many genes involved in cell motility and remodeling of the extracellular matrix are expressed predominantly in M phase, indicating a mechanism for balancing proliferative and invasive cellular behavior. Transcripts upregulated during S phase displayed extensive overlap with genes induced by DNA damage; cell-cycle-regulated transcripts may therefore constitute coherent programs used in response to external stimuli. Our data also provide clues to biological function for hundreds of previously uncharacterized human genes.
PDF
