Journal of internal medicine
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Lefamulin is a novel antibiotic agent within the pleuromutilin derivative class approved for the treatment of community-acquired bacterial pneumonia (CABP) by the United States Food and Drug Administration and the European Commission in 2019 and 2020, respectively. The objective of this article is to provide a summary of clinically relevant data underlying lefamulin and to provide recommendations for its place in therapy. In vitro data establish lefamulin's activity against a number of Gram-positive, Gram-negative and atypical organisms relevant in the treatment of CABP, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila pneumoniae. ⋯ Pooled and post hoc analyses have confirmed these effects for a variety of subgroups and secondary endpoints. Real-world study data post-approval have largely not yet emerged for lefamulin, and there is a need for further investigation into safety/efficacy for off-label indications such as acute bacterial skin and skin structure infections and sexually transmitted infections. Further data regarding tolerability, particularly with long-term use, as well as the emergence of resistance over time, are still undefined.
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Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS-CoV-2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS-CoV-2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow-up of the pandemic. ⋯ SARS-CoV-2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a).
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Pregnancy in women with acute hepatic porphyria (AHP) has historically been associated with significant morbidity. Clinical outcomes have been the focus of previous reports on porphyria and maternal health, with little data available on the levels of heme precursors during pregnancy. We present the results of a follow-up program for women with AHP in the Swedish cohort who were pregnant between 2001 and 2020. ⋯ Our observations align with contemporary reports that pregnancy in patients with AHP is frequently uncomplicated. Excretion of heme precursors increased during pregnancy, but this did not manifest as a higher frequency of clinical porphyria manifestations. The involvement of porphyria specialists in the patients' maternal care is recommended for reducing risk and improving the probability of good pregnancy outcomes.
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Essential hypertension is a complex trait where the underlying aetiology is not completely understood. Left untreated it increases the risk of severe health complications including cardiovascular and renal disease. It is almost 15 years since the first genome-wide association study for hypertension, and after a slow start there are now over 1000 blood pressure (BP) loci explaining ∼6% of the single nucleotide polymorphism-based heritability. ⋯ Drug re-purposing opportunities, including SLC5A1 and canagliflozin (a type-2 diabetes drug), are also being identified. In this review, we present key studies from the past, highlight current avenues of research and look to the future focusing on gene discovery, epigenetics, gene-environment interactions, GRSs and drug discovery. We evaluate limitations affecting BP genetics, including ancestry bias and discuss streamlining of drug target discovery and applications for treating and preventing hypertension, which will contribute to tailored precision medicine for patients.