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Background
In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).Methods
This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.Results
The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.Conclusions
These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.Plain Language Summary
- Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
- Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
- Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
- Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.
Background
Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19. 相似文献Background
Nursing Home Compare (NHC) ratings, created and maintained by Medicare, are used by both hospitals and consumers to aid in the skilled nursing facility (SNF) selection process. To date, no studies have linked NHC ratings to actual episode-based outcomes. The purpose of this study was to evaluate whether NHC ratings are valid predictors of 90-day complications, readmission, and bundle costs for patients discharged to an SNF after primary total joint arthroplasty (TJA).Methods
All SNF-discharged primary TJA cases in 2017 at a multihospital academic health system were queried. Demographic, psychosocial, and clinical variables were manually extracted from the health record. Medicare NHC ratings were then collected for each SNF. For patients in the Medicare bundle, postacute and total bundle cost was extracted from claims.Results
Four hundred eighty-eight patients were discharged to a total of 105 unique SNFs. In multivariate analysis, overall NHC rating was not predictive of 90-day readmission/major complications, >75th percentile postacute cost, or 90-day bundle cost exceeding the target price. SNF health inspection and quality measure ratings were also not predictive of 90-day readmission/major complications or bundle performance. A higher SNF staffing rating was independently associated with a decreased odds for >75th percentile 90-day postacute spend (odds ratio, 0.58; P = .01) and a 90-day bundle cost exceeding the target price (odds ratio = 0.69; P = .02) but was similarly not predictive of 90-day readmission/complications.Conclusion
Results of our study suggest that Medicare's NHC tool is not a useful predictor of 90-day costs, complications, or readmissions for SNFs within our health system. 相似文献Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.
Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available. 相似文献