Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: a cohort study.

AIM: To compare pancreatic cancer incidence and diagnostic evaluation among patients initiating dipeptidyl-peptidase-4 (DPP-4) inhibitor treatment with those initiating sulfonylureas (SU) and thiazolidinediones (TZD). METHODS: Medicare claims data were examined in a new-user active-comparator cohort study. Patients >65 years with no prescriptions for DPP-4 inhibitors, SU or TZD at baseline were included if they had at least two claims for the same drug within 180 days. Using an as-treated approach and propensity score-adjusted Cox models, we estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for pancreatic cancer. Diagnostic evaluations were compared using risk ratios. RESULTS: In the DPP-4 inhibitor versus SU comparison, there were 18 179 patients who initiated treatment with DPP-4 inhibitors, of whom 26 developed pancreatic cancer (interquartile range follow-up 5-18 months). In the DPP-4 inhibitor versus TZD comparison there were 29 366 people initiating DPP-4 inhibitor treatment and 52 of these developed pancreatic cancer. The risk of pancreatic cancer with DPP-4 inhibitor treatment was lower relative to SU treatment (HR: 0.6, CI: 0.4-0.9) and similar to TZD treatment (HR: 1.0, 95% CI: 0.7-1.4). After the first 6 months of follow-up were excluded to reduce the potential for reverse causality, the results were not altered. The probability of diagnostic evaluation after commencing DPP-4 inhibitor treatment (79.3%) was similar to that for TZD (74.1%, risk ratio 1.06, 95% CI: 1.05-1.07) and SU (74.6%) (risk ratio 1.06, 95% CI: 1.05-1.07). The probability of diagnostic evaluation before the index date (date of initiating treatment) was ∼80% for all cohorts. CONCLUSION: Although the present study was limited by sample size and the observed duration of treatment in the USA, our well-controlled population-based study suggests there is no higher short-term pancreatic cancer risk with DPP-4 inhibitor treatment relative to SU or TZD treatment.

Antidepressant class, age, and the risk of deliberate self-harm: a propensity score matched cohort study of SSRI and SNRI users in the USA.

BACKGROUND: The US Food and Drug Administration's meta-analyses of placebo-controlled antidepressant trials found approximately twice the rate of suicidal behaviors among children and adults aged 24 years and younger who were randomized to receive antidepressant medication than among those who were randomized to placebo. Rates of suicidal behavior were similar for subjects aged 25-64 years whether they received antidepressants or placebo, and subjects aged 65 years or older randomized to antidepressants were found to have lower rates of suicidal behavior. The age-stratified FDA meta-analyses did not have adequate power to investigate rates of suicidal behaviors by antidepressant drug class. OBJECTIVE: Our objective was to assess the risk of deliberate self-harm associated with the two most commonly prescribed classes of antidepressant agents. DESIGN: Propensity score matched cohort study of incident users of antidepressant agents. SETTING: Population-based healthcare utilization data of US residents. PATIENTS: US residents aged 10-64 years with a recorded diagnosis of depression who initiated use of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) between 1 January 1998 and 31 December 2010. MAIN OUTCOME MEASURES: ICD-9 external cause of injury codes E950.x-E958.x (deliberate self-harm). RESULTS: A total of 102,647 patients aged between 10 and 24 years, and 338,021 aged between 25 and 64 years, initiated therapy with antidepressants. Among 10-24 year olds, prior to propensity score matching, 75,675 initiated therapy with SSRIs and 5,344 initiated SNRIs. After matching, there were 5,344 SNRI users and 10,688 SSRI users. Among the older cohort, 36,037 SNRI users were matched to 72,028 SSRI users (from an unmatched cohort of 225,952 SSRI initiators). Regardless of age cohort, patients initiating SSRIs and patients initiating SNRIs had similar rates of deliberate self-harm. Restriction to patients with no antidepressant use in the past 3 years did not alter our findings. CONCLUSIONS: Our findings of similar rates of deliberate self-harm for depressed patients who initiate treatment with either an SSRI or an SNRI suggests that physicians who have decided that their patients would benefit from initiating antidepressant therapy need not weigh differential suicide risk when deciding which class of antidepressant to prescribe.

Temperature can alter the function outcome of spinal cord regeneration in larval lampreys.

Now that spinal cord regeneration has been demonstrated in mammals [Bregman B. S. et al. (1995) Nature 378, 498-501; Cheng H. et al. (1996) Science 273, 510-513], we must examine the consequences and look for means of avoiding negative outcomes. The larval lamprey, which readily regenerates cut spinal axons, offers a model for this important next step. In the present study, one group of larval lampreys with spinal lesions was kept at room temperature during recovery. Another group was returned to their usual cold room temperature. A majority of animals kept at room temperature recovered full locomotor behavioral function, while a majority of those that recovered at a colder temperature exhibited dysfunctional locomotor behavior. The dysfunction most often consisted of segments rostral and caudal to the lesion site lacking the usual coordination and apparently interfering with each. In both groups, there was a close association between the presence of dysfunction and the quality of the intersegmental coordination as assessed in the isolated spinal cord preparation. These results suggest that a relatively minor difference in conditions under which an animal recovers may drastically alter the likelihood of a favorable functional outcome.

Exstrophy of the bladder. I. Long-term results in a series of 37 cases treated by ureterosigmoidostomy.

Of the 37 patients with exstrophy of the bladder in whom ureterosigmoidostomy was selected as the mainstay of treatment 4 died of causes related to the procedure. Faulty judgment and poor followup accounted for these deaths, which might well be preventable today. In 18 survivors, or approximately half of the entire series, the operation has held up well for many years, with no further surgical procedure being required for complications. In 12 patients, or approximately a third of the group, remedial operations for complications attributable to the ureterosigmoidostomy have been required but it was elected to retain this form of diversion. The long-term end result in these patients also remains acceptable. Combining these 2 groups 30 of 37 patients with ureterosigmoidostomy may be considered to have been eventually successful. However, in 7 of 37 patients the method was a frank failure, in that 4 patients died and 3 required substitution of another form of diversion. While all forms of treatment of exstrophy of the bladder leave much to be desired, results obtainable in today's setting lead us to recommend ureterosigmoidostomy as first choice in the management of this disorder. This recommendation is accompanied by the admonition that systematic followup is imperative so that if things do go badly from the clinical, laboratory or urographic viewpoint corrective measures can be done before renal deterioration occurs. The measures required may range from simple correction of electrolytes to conversion to an ileal loop.