Incidence and pattern of mycophenolate discontinuation associated with abnormal monitoring blood-test results: cohort study using data from the Clinical Practice Research Datalink Aurum

Abstract Objective To examine the incidence and pattern of mycophenolate discontinuation associated with abnormal monitoring blood-tests. Methods Data from people prescribed mycophenolate for common inflammatory conditions in the Clinical Practice Research Datalink was used. Participants were followed from first mycophenolate prescription. Primary outcome was drug discontinuation with an associated abnormal blood-test result within 60 days. Secondary outcomes were drug discontinuation for any reason, and discontinuations associated with severely abnormal blood-test results within 60 days. Multivariable cox-regression was used to examine factors associated with primary outcome. Results The cohort included 992 participants (68.9% female, mean age 51.95 years, 47.1% with SLE) contributing 1,885 person-years of follow-up. The incidence of mycophenolate discontinuation associated with any (severely) abnormal blood-test results was 153.46 (21.07) per 1000 person-years in the first, and 32.39 (7.91) per 1000 person-years in later years of prescription, respectively. 11.5% (1.7%) patients prescribed mycophenolate discontinued treatment with any (severely) abnormal blood-test results in the first year of prescription. After this period mean 2.6% (0.7%) patients discontinued treatment with any (severely) abnormal blood-test results per year. Increased serum creatinine and cytopenia were more commonly associated with mycophenolate discontinuation than elevated liver enzymes. CKD-stage ≥3 was significantly associated with mycophenolate discontinuation with any blood-test abnormalities (aHR (95%CI) 2.22 (1.47–3.37)). Conclusion Mycophenolate is uncommonly discontinued for blood-test abnormalities, and, even less often discontinued for severe blood-test abnormalities after the first year of prescription. Consideration may be given for less frequent monitoring after one-year of treatment, especially in those without CKD-stage ≥3. </jats:sec

Mortality after infection with methicillin-resistant Staphylococcus aureus (MRSA) diagnosed in the community

<p>Abstract</p> <p>Background</p> <p>Outbreak reports suggest that community-acquired methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) infections can be life-threatening. We conducted a population based cohort study to assess the magnitude of mortality associated with MRSA infections diagnosed in the community.</p> <p>Methods</p> <p>We used the United Kingdom's General Practice Research Database (GPRD) to form a cohort of all patients with MRSA diagnosed in the community from 2001 through 2004 and up to ten patients without an MRSA diagnosis. The latter were frequency-matched with the MRSA patients on age, GPRD practice and diagnosis date. All patients were older than 18 years, had no hospitalization in the 2 years prior to cohort entry and medical history information of at least 2 years prior to cohort entry. The cohort was followed up for 1 year and all deaths and hospitalizations were identified. Hazard ratios of all-cause mortality were estimated using the Cox proportional hazards model adjusted for patient characteristics.</p> <p>Results</p> <p>The cohort included 1439 patients diagnosed with MRSA and 14,090 patients with no MRSA diagnosis. Mean age at cohort entry was 70 years in both groups, while co-morbid conditions were more prevalent in the patients with MRSA. Within 1 year, 21.8% of MRSA patients died as compared with 5.0% of non-MRSA patients. The risk of death was increased in patients diagnosed with MRSA in the community (adjusted hazard ratio 4.1; 95% confidence interval: 3.5–4.7).</p> <p>Conclusion</p> <p>MRSA infections diagnosed in the community are associated with significant mortality in the year after diagnosis.</p

Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

<p>Abstract</p> <p>Background</p> <p>Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with <it>Klebsiella pneumoniae</it>, and 2) the phagocytic ability of macrophages from these mice.</p> <p>Methods</p> <p>Male and female C57BL/6 mice were exposed to O₃or to filtered air (FA) (control) and then infected intratracheally with <it>K. pneumoniae </it>bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen <it>in vivo </it>was investigated after 1 h.</p> <p>Results</p> <p>1) Both male and female mice exposed to O₃are significantly more susceptible to <it>K. pneumoniae </it>infection than mice treated with FA; 2) although females appeared to be more resistant to <it>K. pneumoniae </it>than males, O₃exposure significantly increased the susceptibility of females to <it>K. pneumoniae </it>infection to a greater degree than males; 3) alveolar macrophages from O₃-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O₃-dependent reduction in phagocytic ability is greater in female mice.</p> <p>Conclusion</p> <p>O₃exposure reduces the ability of mice to survive <it>K. pneumoniae </it>infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.</p

Circadian oscillator proteins across the kingdoms of life : Structural aspects 06 Biological Sciences 0601 Biochemistry and Cell Biology

Circadian oscillators are networks of biochemical feedback loops that generate 24-hour rhythms and control numerous biological processes in a range of organisms. These periodic rhythms are the result of a complex interplay of interactions among clock components. These components are specific to the organism but share molecular mechanisms that are similar across kingdoms. The elucidation of clock mechanisms in different kingdoms has recently started to attain the level of structural interpretation. A full understanding of these molecular processes requires detailed knowledge, not only of the biochemical and biophysical properties of clock proteins and their interactions, but also the three-dimensional structure of clockwork components. Posttranslational modifications (such as phosphorylation) and protein-protein interactions, have become a central focus of recent research, in particular the complex interactions mediated by the phosphorylation of clock proteins and the formation of multimeric protein complexes that regulate clock genes at transcriptional and translational levels. The three-dimensional structures for the cyanobacterial clock components are well understood, and progress is underway to comprehend the mechanistic details. However, structural recognition of the eukaryotic clock has just begun. This review serves as a primer as the clock communities move towards the exciting realm of structural biology

MIS-Schottky theory under conditions of optical carrier generation in solar cells

The theory of MIS-Schottky barriers and their electrical characteristics is examined for its application to solar cells. It is found that the interface behavior of contacts forward-biased by illumination is qualitatively different from that of the same contacts biased in the dark by an applied forward voltage. Observed increases due to the interfacial layer in the open-circuit voltage of the solar cell cannot therefore be associated with increases in the "n value" measured for the dark current, but rather are due to the different effects of this layer on the transport properties of majority and minority carriers. The theory predicts an optimum thickness for the interfacial layer above which the short-circuit (minority-carrier) current decreases, and the efficiency (fill factor) is degraded.link_to_subscribed_fulltex

Peaked schottky-barrier solar cells by Al-Si metallurgical reactions

The dark currents in Al-nSi Schottky-barrier solar cells are appreciably reduced by low-temperature heat treatments (T<577°C) which induce metallurgical reactions between the Al and Si. Open-circuit voltages of these cells can be increased by more than 0.2 V as a result of this mechanism.link_to_subscribed_fulltex

EFFECT OF ILLUMINATION ON THE DEPLETION-REGION RECOMBINATION CURRENTS IN SCHOTTKY-BARRIER SOLAR CELLS.

The danger of using dark currents in a calculation of the Schottky-barrier solar cell characteristics is demonstrated experimentally. Recombination in the depletion region provides an illumination-dependent contribution which detracts from the collected minority carrier current in Au-n Si (single crystal) cells.link_to_subscribed_fulltex