Drugs
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Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and CKD is considered a coronary artery disease risk equivalent. So far, statins have been the mainstay of primary and secondary prevention of cardiovascular disease in the general population. However, their benefit on outcomes is limited and controversial in CKD patients and new therapeutic approaches to reduce cardiovascular risk are needed. ⋯ In CKD sub-group analysis, ODYSSEY COMBO I and ODYSSEY COMBO II studies demonstrated significant superiority of alirocumab on LDL-cholesterol lowering in comparison to placebo and ezetimibe, respectively, when added to statins, and case reports have shown efficacy in nephrotic syndrome. A detailed analysis of CKD subgroups in general population trials of anti-PCSK9 strategies addressing events is needed, given the limited efficacy of statins in CKD both in terms of lipid lowering and events, the high rate of statin non-compliance in these patients, and the high lipoprotein(a) levels. This information should guide the design of trials addressing the safety profile and efficacy on cardiovascular outcomes of PCSK9-targeted therapies in CKD patients.
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Relebactam (formerly known as MK-7655) is a non-β-lactam, bicyclic diazabicyclooctane, β-lactamase inhibitor that is structurally related to avibactam, differing by the addition of a piperidine ring to the 2-position carbonyl group. Vaborbactam (formerly known as RPX7009) is a non-β-lactam, cyclic, boronic acid-based, β-lactamase inhibitor. The structure of vaborbactam is unlike any other currently marketed β-lactamase inhibitor. ⋯ Potential roles in therapy for these agents include the treatment of suspected or documented infections caused by resistant Gram-negative bacilli-producing ESBL, KPC, and/or AmpC β-lactamases. The usage of these agents in patients with CRE infections will likely become the standard of care. Finally, increased activity of imipenem-relebactam against P. aeruginosa may be of clinical benefit to patients with suspected or documented P. aeruginosa infections.
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The opioid epidemic is an escalating health crisis. We evaluated the impact of opioid prescription rates and socioeconomic determinants on opioid mortality rates, and identified potential differences in prescription patterns by categories of practitioners. ⋯ The prescription opioid rate, and especially that by certain categories of prescribers, correlated with opioid-related mortality. Interventions should prioritize providers that have a disproportionate impact and those that care for populations with socioeconomic factors that place them at higher risk.
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Review
Pharmacological Approach to the Management of Crohn's Disease Patients with Perianal Disease.
Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. ⋯ However, response is inadequate in up to half of cases. A possible role of new biological drugs in this context (vedolizumab, ustekinumab) is an area of ongoing investigation, as is the local application of autologous or allogeneic mesenchymal stem cells. These are non-hematopoietic multipotent cells with anti-inflammatory and immunomodulatory properties, the use of which may successfully treat refractory patients, and seem to be a promising and safe alternative to achieving fistula healing in Crohn's disease, without known systemic effects.
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A 1-month formulation of the gonadotrophin-releasing hormone agonist (GnRHa) triptorelin (Decapeptyl®) has been approved in the EU as an adjuvant treatment in combination with tamoxifen or an aromatase inhibitor (AI), of endocrine-responsive, early-stage breast cancer in women at high risk of recurrence who are confirmed as premenopausal after completion of chemotherapy. This indication reflects the results of the 5-year SOFT and TEXT studies, especially SOFT, in which ovarian function suppression (OFS; mainly achieved with triptorelin) added to tamoxifen provided a significant benefit in the overall study population of premenopausal patients only after adjusting for prognostic factors. It emerged that adding OFS to tamoxifen produced more pronounced benefits in terms of disease control and, furthermore, increased overall survival in the cohort of higher-risk patients who had previously received chemotherapy. ⋯ Nonetheless, the two combinations had distinct tolerability profiles (e.g. vasomotor symptoms and thromboembolic events were more frequent with OFS plus tamoxifen, whereas musculoskeletal symptoms, decreased libido, osteoporosis and fractures were more frequent with OFS plus exemestane). Thus, the combinations of OFS (with triptorelin) plus either tamoxifen or an AI are valid options for the adjuvant treatment of endocrine-responsive, early-stage breast cancer in women at sufficiently high risk of relapse to warrant receiving chemotherapy and who remain premenopausal thereafter. Individualized weighing of the potential benefits and adverse effects of treatment is required.