NSAIDs and Renal Impairment: Deprescribing Chronic NSAID use in General Practice.

Aim NSAIDs are high-risk medicines that can commonly cause adverse renal effects. Recent evidence suggests a rise in the number of patients with acute and chronic renal disease. The aim of this audit is to determine our de-prescribing rate of chronic NSAID use in an Irish general practice. Methods We reviewed NSAID-containing drug prescriptions that were issued over a three month period in 2018. A description analysis was performed to ascertain for the frequency and type of NSAIDs prescribed. An educational session was delivered to clinicians to encourage de-prescribing of NSAIDs if deemed clinically appropriate. Results Fifty-one NSAID-containing prescriptions were identified. Thirty-six (71%) patients, who were prescribed a regular NSAID, were aged between 71-85 years. Meloxicam was used the most (31%), whilst the preferred NSAIDs (naproxen and ibuprofen) were used least (18%). A 37% improvement in de-prescribing of chronic NSAIDs was achieved upon re-auditing. Conclusion NSAIDs are commonly implicated in inappropriate prescribing. Clinicians are encouraged to practice de-prescribing at every opportunity. Recent evidence suggests that pharmacy-led educational interventions can further assist de-prescribing of inappropriate medicines. Thus, a close collaboration between physicians and pharmacists is encouraged to further maximise quality of prescribing and patient care.

A Descriptive Study of Antidepressant Prescribing In a Semi-Rural Practice

Aims Mental health conditions are increasingly encountered in general practice. The aim of this study was to review the antidepressant prescribing of this practice. Methods Health One analysis was used to search for patients prescribed antidepressants in the last 6 months and to generate a list of their antidepressant prescriptions over the last three years. Charts were reviewed to determine if these patients were reviewed by a GP in the last 6 months, and by psychiatry in the last year. Results Six hundred and two patients (7% of the practice adult population) were prescribed antidepressants in the last 6 months. Fifty-four percent (n=324) of patients have been on antidepressants for three years or more. Escitalopram was most frequently prescribed. 89% (n=535) were reviewed by a GP in the last 6 months, and 21% (n=127) were reviewed by psychiatry services in the last year. Discussion The majority of patients with mental health problems are being managed in primary care.

Recombinant measles viruses expressing altered hemagglutinin (H) genes: functional separation of mutations determining H antibody escape from neurovirulence.

Measles virus (MV) strain CAM/RB, which was adapted to growth in the brain of newborn rodents, is highly neurovirulent. It has been reported earlier that experimentally selected virus variants escaping from the monoclonal antibodies (MAbs) Nc32 and L77 to hemagglutinin (H) preserved their neurovirulence, whereas mutants escaping MAbs K71 and K29 were found to be strongly attenuated (U. G. Liebert et al., J. Virol. 68:1486-1493, 1994). To investigate the molecular basis of these findings, we have generated a panel of recombinant MVs expressing the H protein from CAM/RB and introduced the amino acid substitutions thought to be responsible for antibody escape and/or neurovirulence. Using these recombinant viruses, we identified the amino acid changes conferring escape from the MAbs L77 (377R-->Q and 378M-->K), Nc32 (388G-->S), K71 (492E-->K and 550S-->P), and K29 (535E-->G). When the corresponding recombinant viruses were tested in brains of newborn rodents, we found that the mutations mediating antibody escape did not confer differential neurovirulence. In contrast, however, replacement of two different amino acids, at positions 195G-->R and 200S-->N, which had been described for the escape mutant set, caused the change in neurovirulence. Thus, antibody escape and neurovirulence appear not to be associated with the same structural alterations of the MV H protein.

The H gene of rodent brain-adapted measles virus confers neurovirulence to the Edmonston vaccine strain.

Molecular determinants of neuropathogenesis have been shown to be present in the hemagglutinin (H) protein of measles virus (MV). An H gene insertion vector has been generated from the Edmonston B vaccine full-length infectious clone of MV. Using this vector, it is possible to insert complete H open reading frames into the parental (Edtag) background. The H gene from a rodent brain-adapted MV strain (CAM/RB) was inserted into this vector, and a recombinant virus (EdtagCAMH) was rescued by using a modified vaccinia virus which expresses T7 RNA polymerase (MVA-T7). The recombinant virus grew at an equivalent rate and to similar titers as the CAM/RB and Edtag parental viruses. Neurovirulence was assayed in a mouse model for MV encephalitis. Viruses were injected intracerebrally into the right cortex of C57/BL/6 suckling mice. After infection mice inoculated with the CAM/RB strain developed hind limb paralysis and ataxia. Clinical symptoms were never observed with an equivalent dose of Edtag virus or in sham infections. Immunohistochemistry (IHC) was used to detect viral antigen in formalin-fixed brain sections. Measles antigen was observed in neurons and neuronal processes of the hippocampus, frontal, temporal, and olfactory cortices and neostriatum on both sides of symmetrical structures. Viral antigen was not detected in mice infected with Edtag virus. Mice infected with the recombinant virus, EdtagCAMH, became clinically ill, and virus was detected by IHC in regions of the brain similar to those in which it was detected in animals infected with CAM/RB. The EdtagCAMH infection had, however, progressed much less than the CAM/RB virus at 4 days postinfection. It therefore appears that additional determinants are encoded in other regions of the MV genome which are required for full neurovirulence equivalent to CAM/RB. Nevertheless, replacement of the H gene alone is sufficient to cause neuropathology.

Identification of increased amounts of UDP-glucuronyltransferase protein in phenobarbital-treated chick-embryo liver cells.

UDP-glucuronyltransferase activity of neonatal-chick liver or phenobarbital-treated chick-embryo liver catalysed the glucuronidation of 1-naphthol, 4-nitrophenol and 2-aminophenol. Only low transferase activity towards testosterone was detected, and activity towards bilirubin was not detectable. Liver microsomal transferase activity towards the three phenols was increased approx. 20-50-fold by phenobarbital treatment of chick embryos or by transfer of liver cells into tissue culture. A single form of UDP-glucuronyltransferase, which appears to catalyse the glucuronidation of these three phenols, was purified to near homogeneity from phenobarbital-treated chick-embryo liver microsomal fraction for the first time. The use of this purified enzyme as a standard protein facilitated the identification of this protein in chick-embryo liver microsomal fraction. Further, the accumulation of this microsomal protein was observed following phenobarbital treatment of chick embryos and during tissue culture of chick-embryo liver cells. The value of this model system for the study of the induction of UDP-glucuronyltransferase by drugs and hormones is discussed.