ObjectiveTo determine the safety of ciprofloxacin in paediatric patients in relation to arthropathy, any other adverse events (AEs) and drug interactions.MethodsA systematic search of MEDLINE, EMBASE, CINAHL, CENTRAL and bibliographies of relevant articles was carried out for all published articles, regardless of design, that involved the use of ciprofloxacin in any paediatric age group ≤17 years. Only articles that reported on safety were included.Results105 articles met the inclusion criteria and involved 16 184 paediatric patients. There were 1065 reported AEs (risk 7%, 95% CI 3.2% to 14.0%). The most frequent AEs were musculoskeletal AEs, abnormal liver function tests, nausea, changes in white blood cell counts and vomiting. There were six drug interactions (with aminophylline (4) and methotrexate (2)). The only drug related death occurred in a neonate who had an anaphylactic reaction. 258 musculoskeletal events occurred in 232 paediatric patients (risk 1.6%, 95% CI 0.9% to 2.6%). Arthralgia accounted for 50% of these. The age of occurrence of arthropathy ranged from 7 months to 17 years (median 10 years). All cases of arthropathy resolved or improved with management. One prospective controlled study estimated the risk of arthropathy as 9.3 (OR 95% CI 1.2 to 195). Pooled safety data of controlled trials in this review estimated the risk of arthropathy as 1.57 (OR 95% CI 1.26 to 1.97).ConclusionMusculoskeletal AEs occur due to ciprofloxacin use. However, these musculoskeletal events are reversible with management. It is recommended that further prospective controlled studies should be carried out to evaluate the safety of ciprofloxacin, with particular focus on the risk of arthropathy.

SUMMARY Objective Gestational diabetes (GDM) is characterized by maternal glucose intolerance that manifests during pregnancy. Because GDM resembles type 2 diabetes (T2DM), shared genetic predisposition is likely but has not been established. We tested the hypothesis that a genetic risk score (GRS) that included variants known to be associated with T2DM is associated with GDM. Study design We conducted a case-control study using the Vanderbilt Medical Center biobank (BioVU), and calculated a simple-count GRS using 34 variants previously associated with T2DM or fasting glucose in the general population, or with GDM or glucose intolerance in pregnancy. We assessed the association of the GRS with GDM adjusting for maternal age, parity, and body mass index (BMI) and calculated the area under the curve for the receiver-operating characteristic curve (c-statistic). Study population Among Caucasian women, we identified 458 cases of GDM and 1538 pregnant controls with normal glucose tolerance. Results Cases of GDM had a higher number of risk alleles compared to controls (38.9±4.0 vs. 37.4 ± 4.0 risk alleles, P=1.6x10−11). The GRS was significantly associated with GDM; the adjusted odds ratio associated with each additional risk allele was 1.10 (95% CI, 1.07-1.13, P=6x10−11). Clinical variables predicted the risk for GDM (c-statistic 0.67, 95% CI: 0.64 - 0.70), and adding the GRS modestly improved prediction (0.70, 95% CI: 0.67 - 0.73). Conclusions Among Caucasian women, a GRS that included common T2DM genetic risk variants was associated with increased risk of GDM but showed limited utility in the identification of GDM cases.

African Americans have increased hemodynamic responses to both physiologic and pharmacologic adrenergic stimulation compared to Caucasians, and this may contribute to the greater prevalence of hypertension in this ethnic group. A small study suggested enhanced α1-adrenoreceptor-mediated arterial vasoconstriction in the forearm vasculature of African Americans compared to Caucasians, but it is unknown whether this reflects a generalized vascular phenomenon. The objective of this study was to examine the hypothesis that there are ethnic differences in venous α1-adrenoreceptor responsiveness. Using a linear variable differential transformer, we measured local dorsal hand vein responses to increasing doses of the selective α1-adrenoreceptor agonist, phenylephrine, in 106 subjects (64 Caucasians and 42 African Americans). There was wide interindividual variability in responses to phenylephrine. The dose that produced 50% of maximal constriction (ED50) ranged from 11 to 5442 ng/min, and maximal venoconstriction (Emax) ranged from 13.5% to 100%. African Americans (geometric mean ED50=172 ng/min; 95% CI, 115 to 256 ng/min) were more sensitive to phenylephrine than Caucasians (310 ng/min; 95% CI, 222 to 434 ng/min; unadjusted P=0.026; adjusted P=0.003). Median Emax was slightly higher in African Americans (89%; IQR, 82% to 98%) compared to Caucasians (85%; IQR, 75% to 95%; P=0.07). Taken together with previous findings in arterial vessels, our results suggest a generalized increased sensitivity to α1-adrenoreceptor-mediated vasoconstriction in African Americans. Increased vascular α-adrenoreceptor sensitivity could predispose to hypertension, and future studies addressing this mechanism’s contribution to ethnic differences in the prevalence of hypertension will be of interest.