A reanalysis of apatite fission track (AFT) thermochronology coupled with thermal‐kinetic modeling of samples from the Wind River Range document Late Cretaceous to early Eocene episodic cooling and exhumation of one of the largest basement‐cored ranges in the western United States. Three vertical transects taken at different latitudes along the length of the 145 km Wind River Range reveal that exhumation is uniform along strike suggesting steady displacement along the Wind River Fault, and significant exhumation and relief in the Wind River Range by the early Eocene. Thermal modeling of AFT ages, lengths, and compositional proxies document rapid exhumation from ~65 to 50 Ma. This rapid exhumation episode matches a period of accelerated subsidence in the adjacent Green River and Wind River basins. At ~50 Ma, exhumation dramatically slowed by an order of magnitude coincident with decreasing subsidence in the adjacent basins. No signal of Oligocene cooling is apparent in either AFT cooling ages or thermal modeling suggesting that a possible later phase of reactivation of structures and uplift, as previously suggested, was limited to less than approximately 1 km of exhumation.
BackgroundMany patients with acromegaly require medical treatment that includes somatostatin analogs (SSAs). Long-acting SSA formulations are widely used, due in part to increased patient convenience and increased treatment adherence vs daily medications. Although medication compliance can be poor in patients with chronic conditions, adherence and persistence with these SSAs in patients with acromegaly has not been evaluated. This analysis utilized claims data to estimate treatment adherence and persistence for lanreotide depot and long-acting octreotide in this population.MethodsThis retrospective analysis used the MarketScan® database (~100 payors, 500 million claims in the US), which was searched between January 2007 and June 2012 to identify patients with acromegaly taking either lanreotide depot or long-acting octreotide. Patients switching treatments were excluded. Treatment adherence was assessed using medication possession ratio (MPR; number of doses dispensed in relation to dispensing period; ≥80% is considered adherent), injection count, and treatment time. Persistence was estimated by Kaplan-Meier analyses and Cox proportional hazards modeling. A washout period, defined as no acromegaly-related prescription activity 180 days prior to the index date, was employed to minimize effects of prior therapy and focus on patients more likely to be treatment-naïve.ResultsAltogether 1308 patients with acromegaly receiving a single SSA for treatment (1127 octreotide, 181 lanreotide) who had not switched treatments were identified. Mean MPR in patients with a 180-day washout (n = 663) was 89% for those receiving octreotide (n = 545) and 87% for those receiving lanreotide (n = 118). Median number of days on therapy was 169 (95% CI 135–232) for octreotide patients and 400 (95% CI 232–532) for lanreotide patients. The point estimate of the Cox proportional hazard ratio for stopping treatment was 1.385 for octreotide vs lanreotide (95% CI 1.079–1.777), suggesting a 38.5% increased risk for stopping octreotide before lanreotide.ConclusionsTreatment adherence was similarly good for both injectable SSA treatments studied, at 87% or greater. Persistence was greater with lanreotide than octreotide and the risk of discontinuing therapy was lower with lanreotide than octreotide. Further studies to determine factors leading to these differences in persistence or to predict discontinuation of therapy may aid in clinical management of these patients.
This study assessed the total costs of testing, including the estimated costs of delaying care, associated with next-generation sequencing (NGS) versus single-gene testing strategies among patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) from a Canadian public payer perspective. A decision tree model considered testing for genomic alterations using tissue biopsy NGS or single-gene strategies following Canadian guideline recommendations. Inputs included prevalence of mNSCLC, the proportion that tested positive for each genomic alteration, rebiopsy rates, time to test results, testing/medical costs, and costs of delaying care based on literature, public data, and expert opinion. Among 1,000,000 hypothetical publicly insured adult Canadians (382 with mNSCLC), the proportion of patients that tested positive for a genomic alteration with an approved targeted therapy was 38.0% for NGS and 26.1% for single-gene strategies. The estimated mean time to appropriate targeted therapy initiation was 5.1 weeks for NGS and 9.2 weeks for single-gene strategies. Based on literature, each week of delayed care cost CAD 406, translating to total mean per-patient costs of CAD 3480 for NGS and CAD 5632 for single-gene strategies. NGS testing with mNSCLC in current Canadian practice resulted in more patients with an identified mutation, shorter time to appropriate targeted therapy initiation, and lower total testing costs compared to single-gene strategies.
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