Risk of Thyroid Cancer Associated with Use of Liraglutide and Other Antidiabetic Drugs in a US Commercially Insured Population.

BACKGROUND: Quantify association between the glucagon-like peptide-1 receptor agonist liraglutide and risk of thyroid cancer (TC) compared to other antidiabetics. PATIENTS AND METHODS: Initiators of liraglutide, exenatide, metformin, pioglitazone or groups of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US health plan (2010-2014) and followed for a median of 17 months. Thyroid cancer cases during follow-up were identified via a validated algorithm. Incidence rates of TC among liraglutide and comparators were assessed using relative risks estimated within propensity score-matched cohorts using intention to treat (ITT) and time on drug analyses. Latency effects and potential surveillance bias were evaluated. RESULTS: Relative risks from ITT analyses ranged from 1.00 (95% confidence interval (CI) 0.56-1.79) versus metformin to 1.70 (95% CI 1.03-2.81) versus all comparators excluding exenatide. Effect estimates from latency analyses were slightly attenuated. Time on drug analyses suggested no increased risk for either longer duration or higher cumulative dose of liraglutide. Medical record review found 85% were papillary or a follicular variant of papillary or both; 46% were microcarcinomas (≤10 millimeters), which were more prevalent in the liraglutide cohort (67% versus 43% in all comparators). CONCLUSION: Relative risks were elevated for several comparisons, which should be interpreted cautiously because of potential residual confounding and surveillance bias. Liraglutide cases had smaller thyroid nodules and shorter time-to-diagnosis, suggesting increased surveillance for TC among liraglutide initiators, especially shortly after the drug´s approval. After adjusting the primary analyses (ITT) for latency, no significant elevated risk of TC was observed among liraglutide initiators.

Hong Kong Women Project a Larger Body When Speaking to Attractive Men.

In this pilot study we investigated the vocal strategies of Cantonese women when addressing an attractive vs. unattractive male. We recruited 19 young female native speakers of Hong Kong Cantonese who completed an attractiveness rating task, followed by a speech production task where they were presented a subset of the same faces. By comparing the rating results and corresponding acoustic data of the facial stimuli, we found that when young Cantonese women spoke to an attractive male, they were less breathy, lower in fundamental frequency, and with denser formants, all of which are considered to project a larger body. Participants who were more satisfied with their own height used these vocal strategies more actively. These results are discussed in terms of the body size projection principle.

Predictive values of diagnostic codes for identifying serious hypocalcemia and dermatologic adverse events among women with postmenopausal osteoporosis in a commercial health plan database.

BACKGROUND: Post-marketing safety studies of medicines often rely on administrative claims databases to identify adverse outcomes following drug exposure. Valid ascertainment of outcomes is essential for accurate results. We aim to quantify the validity of diagnostic codes for serious hypocalcemia and dermatologic adverse events from insurance claims data among women with postmenopausal osteoporosis (PMO). METHODS: We identified potential cases of serious hypocalcemia and dermatologic events through ICD-9 diagnosis codes among women with PMO within claims from a large US healthcare insurer (June 2005-May 2010). A physician adjudicated potential hypocalcemic and dermatologic events identified from the primary position on emergency department (ED) or inpatient claims through medical record review. Positive predictive values (PPVs) and 95% confidence intervals (CIs) quantified the fraction of potential cases that were confirmed. RESULTS: Among 165,729 patients with PMO, medical charts were obtained for 40 of 55 (73%) potential hypocalcemia cases; 16 were confirmed (PPV 40%, 95% CI 25-57%). The PPV was higher for ED than inpatient claims (82 vs. 24%). Among 265 potential dermatologic events (primarily urticaria or rash), we obtained 184 (69%) charts and confirmed 128 (PPV 70%, 95% CI 62-76%). The PPV was higher for ED than inpatient claims (77 vs. 39%). CONCLUSION: Diagnostic codes for hypocalcemia and dermatologic events may be sufficient to identify events giving rise to emergency care, but are less accurate for identifying events within hospitalizations.

The comparative safety of rosuvastatin: a retrospective matched cohort study in over 48,000 initiators of statin therapy.

PURPOSE: The purpose of this study was to compare incidence rates of hospitalization associated with rhabdomyolysis, myopathy, renal, or hepatic dysfunction, and of in-hospital death, between initiators of rosuvastatin and other statins. METHODS: This was a matched cohort study of statin initiators from the administrative database of a large health insurer in the US, during the first 6 months of rosuvastatin availability with up to 18 months of follow-up. All outcome events were verified by medical record review. Incidence rates, risk ratios, and associated 95% confidence intervals were estimated. RESULTS: From an initial pool of 12,217, 11,249 eligible rosuvastatin initiators were matched to 37,282 initiators of other statins. The incidence rate (IR) per 1000 person-years for rhabdomyolysis was 0.10 [0.00, 0.55] for rosuvastatin initiators (n = 1) and 0.06 [0.01, 0.22] for other statin initiators (n = 2), for a hazard ratio (HR) of 1.98 [0.18, 21.90]. The IR for myopathy was 0.20 [0.02, 0.71] for rosuvastatin initiators (n = 2) and 0.00 [0.00, 0.09] for other statin initiators (n = 0). The IR for renal dysfunction was 1.18 [0.61, 2.06] for rosuvastatin initiators (n = 12) and 1.26 [0.91, 1.71] for other statin initiators (n = 42), for a HR of 0.90 [0.47, 1.73]. The IR for hepatic dysfunction was 0.20 (0.02, 0.71) for rosuvastatin initiators (n = 2) and 0.24 (0.10, 0.47) for other statin initiators (n = 8), for a HR of 0.87 (0.18, 4.14). CONCLUSIONS: This study found no difference between rosuvastatin and the other statins in the incidence of hospitalizations associated with renal or hepatic events, or death. The absolute incidence rates of rhabdomyolysis and myopathy were reassuringly low among all statin initiators but remain too small for firm conclusions to be drawn on any difference between the statins.

Evolutionary history of the genus Listeria and its virulence genes.

The genus Listeria contains the two pathogenic species Listeria monocytogenes and Listeria ivanovii and the four apparently apathogenic species Listeria innocua, Listeria seeligeri, Listeria welshimeri, and Listeria grayi. Pathogenicity of the former two species is enabled by an approximately 9 kb virulence gene cluster which is also present in a modified form in L. seeligeri. For all Listeria species, the sequence of the virulence gene cluster locus and its flanking regions was either determined in this study or assembled from public databases. Furthermore, some virulence-associated internalin loci were compared among the six species. Phylogenetic analyses were performed on a data set containing the sequences of prs, ldh, vclA, and vclB (all directly flanking the virulence gene cluster), as well as the iap gene and the 16S and 23S-rRNA coding genes which are located at different sites in the listerial chromosomes. L. grayi represents the deepest branch within the genus. The remaining five species form two groupings which have a high bootstrap support and which are consistently found by using different treeing methods. One lineage represents L. monocytogenes and L. innocua, while the other contains L. welshimeri, L. ivanovii and L. seeligeri, with L. welshimeri forming the deepest branch. Based on this perception, we tried to reconstruct the evolution of the virulence gene cluster. Since no traces of lateral gene transfer events could be detected the most parsimonious scenario is that the virulence gene cluster was present in the common ancestor of L. monocytogenes, L. innocua, L. ivanovii, L. seeligeri and L. welshimeri and that the pathogenic capability has been lost in two separate events represented by L. innocua and L. welshimeri. This hypothesis is also supported by the location of the putative deletion breakpoints of the virulence gene cluster within L. innocua and L. welshimeri.