Medications Used Routinely in Primary Care to be Dose-Adjusted or Avoided in People With Chronic Kidney Disease: Results of a Modified Delphi Study.

Background: Chronic kidney disease (CKD) affects up to 18% of those over the age of 65 years. Potentially inappropriate medication prescribing in people with CKD is common. Objectives: Develop a pragmatic list of medications used in primary care that required dose adjustment or avoidance in people with CKD, using a modified Delphi panel approach, followed by a consensus workshop. Methods: We conducted a comprehensive literature search to identify potential medications. A group of 17 experts participated in a 3-round modified Delphi panel to identify medications for inclusion. A subsequent consensus workshop of 8 experts reviewed this list to prioritize medications for the development of point-of-care knowledge translation materials for primary care. Results: After a comprehensive literature review, 59 medications were included for consideration by the Delphi panel, with a further 10 medications added after the initial round. On completion of the 3 Delphi rounds, 66 unique medications remained, 63 requiring dose adjustment and 16 medications requiring avoidance in one or more estimated glomerular filtration rate categories. The consensus workshop prioritized this list further to 24 medications that must be dose-adjusted or avoided, including baclofen, metformin, and digoxin, as well as the newer SGLT2 inhibitor agents. Conclusion and Relevance: We have developed a concise list of 24 medications commonly used in primary care that should be dose-adjusted or avoided in people with CKD to reduce harm. This list incorporates new and frequently prescribed medications and will inform an updated, easy to access source for primary care providers.

Antiinflammatory effects of bromodomain and extraterminal domain inhibition in cystic fibrosis lung inflammation.

Significant morbidity in cystic fibrosis (CF) results from chronic lung inflammation, most commonly due to Pseudomonas aeruginosa infection. Recent data suggest that IL-17 contributes to pathological inflammation in the setting of abnormal mucosal immunity, and type 17 immunity-driven inflammatory responses may represent a target to block aberrant inflammation in CF. Indeed, transcriptomic analysis of the airway epithelium from CF patients undergoing clinical bronchoscopy revealed upregulation of IL-17 downstream signature genes, implicating a substantial contribution of IL-17-mediated immunity in CF lungs. Bromodomain and extraterminal domain (BET) chromatin modulators can regulate T cell responses, specifically Th17-mediated inflammation, by mechanisms that include bromodomain-dependent inhibition of acetylated histones at the IL17 locus. Here, we show that, in vitro, BET inhibition potently suppressed Th17 cell responses in explanted CF tissue and inhibited IL-17-driven chemokine production in human bronchial epithelial cells. In an acute P. aeruginosa lung infection murine model, BET inhibition decreased inflammation, without exacerbating infection, suggesting that BET inhibition may be a potential therapeutic target in patients with CF.

Local control of extra-abdominal desmoid tumors: systematic review and meta-analysis.

The local control of desmoid tumors constitutes a continuing treatment dilemma due to its high recurrence rates. The purpose of this systematic review was to critically examine the current treatment of these rare tumors and to specifically evaluate the local failure and response rates of surgery, radiation and systemic therapy. We comprehensively searched the literature for relevant studies across Cinahl, Embase, Medline and the Cochrane databases. Articles were categorized as surgery, radiation, surgery + radiation and systemic therapy (including cytotoxic and non cytotoxic). Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Pooled odd ratios (OR) for comparative studies and weighted proportions with 95% confidence intervals (CI) are reported. Thirty-five articles were included in the final analysis. Weighted mean local failure rates were 22% [95% CI (16-28%)], 35% [95% CI (26-44%)] and 28% [95% CI (18-39%)] for radiation alone, surgery alone and surgery + radiation respectively. In the analysis of comparative studies, surgery and radiation in combination had lower local failure rates than radiation alone [OR 0.7 (0.4, 1.2)] and surgery alone [OR 0.7 (0.4, 1.0)]. Weighted mean stable disease rates were 91% [95% CI (85-96%)] and 52% [95% CI (38-65%)] for non cytotoxic and cytotoxic chemotherapy respectively. The current evidence suggests that surgery alone has a consistently high rate of local recurrence in managing extra-abdominal desmoid tumors. Radiation therapy in combination with surgery improves local control rates. However, the limited data on systemic therapy for this rare tumor suggests the benefit of using both cytotoxic and non cytotoxic chemotherapy to achieve stable disease.

Juveniles on trial.

This article describes common forensic evaluations requested of juvenile court mental health evaluators. There has been a legal shift toward criminalization of juvenile court, with a greater emphasis on rights, abandonment of the rehabilitative model, and greater movement of adolescents into the adult criminal court. A resulting shift has been the redefinition of juvenile court forensic evaluations toward the specificity of adult forensic work. The challenge for evaluators is to refine their knowledge of the forensic standards and bring knowledge of development, assessment, and diagnosis in juveniles and interview techniques appropriate to juveniles to improve the evaluation and forensic reports.