•Almost half (44%) of patients were non-users of hypomethylating agents.•Lower rates of hospitalizations and ER visits were seen for HMA users vs. non-users.•One-third of patients discontinued HMA ...therapy before 4 treatment cycles.•Predictors of early discontinuation included older age and poor performance status.
Previous analyses using the SEER-Medicare database have reported substantial underutilization of hypomethylating agents (HMAs) among patients with higher-risk myelodysplastic syndromes (MDS), and an association between poor HMA persistence and high economic burden. We aimed to compare rates of hospitalizations and emergency room (ER) visits among patients with higher-risk MDS according to use or non-use of HMA therapy, and to explore factors associated with early discontinuation of HMA therapy.
We used the 2010–2016 SEER-Medicare database to identify patients aged ≥66 years with a new diagnosis of refractory anemia with excess blasts (RAEB; a surrogate for higher-risk MDS) between 2011 and 2015. New hospitalizations and ER visits during the 12 months following MDS diagnosis were determined. Treatment discontinuation was defined as stopping HMA therapy before 4 cycles.
Overall, 664 (55.8%) patients were HMA users and 526 (44.2%) non-users. Non-users had more hospitalizations (mean 0.47 vs. 0.30, P < .001) and ER visits (mean 0.69 vs. 0.41, P = .005) per month than HMA users. Among HMA users, 193 (29.1%) discontinued HMA therapy before 4 cycles, and 91 (47.2%) of these after 1 cycle. Older age and poor performance status were associated with higher risk of HMA discontinuation.
An increased rate of hospitalizations and ER visits occurred in HMA non-users vs. HMA users. Approximately one-third of patients discontinued HMA therapy early. Predictors of discontinuation included older age and poor performance status. Novel approaches are needed to improve utilization and persistence with HMA therapy and associated outcomes, particularly among these higher-risk groups.
In this real-world study, non-use of HMAs among higher-risk MDS patients was common and associated with increased hospitalizations and ER visits. Among IV/SC HMA-treated patients, almost one-third discontinued before 4 cycles, and almost half of these after 1 cycle. Predictors of discontinuation included older age and poor performance status. Novel approaches are needed to improve HMA utilization/persistence and associated outcomes.
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma with characteristic histologic features and chromosomal alterations. Although typically indolent, a small ...subset of cases has been reported to exhibit aggressive clinical behavior. We retrospectively identified 33 patients with MTSCC, consisting of 10 cases of locally advanced/metastatic MTSCC (pT3 or N1 or M1) and 23 kidney-confined MTSCC (pT1/T2) without disease recurrence or progression. Utilizing a single-nucleotide polymorphism array and a targeted next-generation sequencing platform, we examined genome-wide molecular alterations in 24 cases, including 11 available samples from 8 patients with locally advanced/metastatic MTSCC. Ten patients with locally advanced/metastatic MTSCC were 8 females (80%) and 2 males (20%). At nephrectomy, 7 of these 10 cases (70%) were pT3 or pN1 while the remaining 3 (30%) were pT1/T2. Eight patients (80%) developed metastases and common sites included lymph node (4, 40%), bone (4, 40%), and retroperitoneum (3, 30%). Four patients died of disease (40%) during follow-up. Locally advanced/metastatic MTSCCs shared typical MTSCC genomic profiles with loss of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, while some exhibited additional complex genomic alterations, most frequently a relative gain of 1q (7/8). Homozygous loss of CDKN2A/B was observed in 3 (38%) locally advanced/metastatic MTSCCs. Tumor necrosis, solid nested/sheet pattern, irregular trabecular/single-file infiltration in a desmoplastic stroma, lymphovascular space invasion, and increased mitotic activity were associated with locally advanced/metastatic MTSCCs (all p < 0.05). Our findings reveal that MTSCCs with aggressive clinical behavior have progressed through clonal evolution; CDKN2A/B deletion and additional complex genomic abnormalities may contribute to this process. Recognizing the morphologic presentation of high-grade MTSCC and evaluating adverse histologic features seen in these tumors can help establish a definitive diagnosis and stratify patients for treatment and prognostication.
Septo-optic dysplasia (SOD) is a congenital disorder characterized by optic nerve, pituitary and midline brain malformations. The clinical presentation of SOD is highly variable with a poorly ...understood etiology. The majority of SOD cases are sporadic, but in rare instances inherited mutations have been identified in a small number of transcription factors, some of which regulate the expression of Sonic hedgehog (Shh) during mouse forebrain development. SOD is also associated with young maternal age, suggesting that environmental factors, including alcohol consumption at early stages of pregnancy, might increase the risk of developing this condition. Here, we address the hypothesis that SOD is a multifactorial disorder stemming from interactions between mutations in Shh pathway genes and prenatal ethanol exposure. Mouse embryos with mutations in the Shh co-receptor, Cdon, were treated in utero with ethanol or saline at embryonic day 8 (E8.0) and evaluated for optic nerve hypoplasia (ONH), a prominent feature of SOD. We show that both Cdon
mutation and prenatal ethanol exposure independently cause ONH through a similar pathogenic mechanism that involves selective inhibition of Shh signaling in retinal progenitor cells, resulting in their premature cell-cycle arrest, precocious differentiation and failure to properly extend axons to the optic nerve. The ONH phenotype was not exacerbated in Cdon
embryos treated with ethanol, suggesting that an intact Shh signaling pathway is required for ethanol to exert its teratogenic effects. These results support a model whereby mutations in Cdon and prenatal ethanol exposure increase SOD risk through spatiotemporal perturbations in Shh signaling activity.
To depict the treatment journey for patients with small cell lung cancer (SCLC) and evaluate health care resource utilization (HCRU) associated with myelosuppression, a complication induced by ...chemotherapy or chemotherapy plus radiation therapy.
This was a descriptive, retrospective study of patients with SCLC aged ≥65 years, identified from linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data curated between January 2012 and December 2015. Treatment types (chemotherapy, radiation therapy, surgery) were classified as first, second, or third line, depending on the temporal sequence in which regimens were prescribed. For each year, the proportions of patients completing 4- or 6-cycle chemotherapy regimens, with hospital admissions associated with myelosuppression, or who used granulocyte colony–stimulating factors (G-CSFs), blood/platelet transfusions, or erythropoiesis-stimulating agents (ESAs), were calculated.
Chemotherapy was administered as initial treatment in 7,807/11,907 (65.6%) patients whose treatment journey was recorded. Approximately one-third (n = 3,985) subsequently received radiation therapy. In total, 5,791 (57.8%) patients completed the guideline-recommended 4–6 cycles of chemotherapy. Among all chemotherapy-treated patients, 10,370 (74.3%) experienced ≥1 inpatient admission associated with myelosuppression (anemia, 7,366 52.8%; neutropenia, 4,642 33.3%; thrombocytopenia, 2,375 17.0%; pancytopenia, 1,983 14.2%). Supportive care interventions included G-CSF (6,756 48.4% patients), ESAs (1,534 11.0%), and transfusions (3,674 26.3%).
Chemotherapy remains a cornerstone of care for patients with SCLC. Slightly over half of patients completed the recommended number of cycles, underscoring the frailty of patients and aggressiveness of SCLC. HCRU associated with myelosuppression was prominent, suggesting a substantial burden on older patients with SCLC.
Trends in Medication Treatment for ADHD Castle, Lon; Aubert, Ronald E.; Verbrugge, Robert R. ...
Journal of attention disorders,
05/2007, Volume:
10, Issue:
4
Journal Article
Peer reviewed
Objective: This study examines demographic trends in the use of medications to treat ADHD in adult and pediatric populations. Method: Using pharmacy claims data for a large population of commercially ...insured Americans, the study measures ADHD treatment prevalence and drug use from 2000 to 2005. Results: In 2005, 4.4% of children (ages 0 to 19) and 0.8% of adults (ages 20 and older) used ADHD medications. Treatment rates were higher in boys (6.1%) than in girls (2.6%), but the rates for men and women were approximately equal (0.8%). During the period of the study, treatment prevalence increased rapidly (11.8% per year) for the population as a whole. Treatment rates grew more rapidly for adults than for children, more rapidly for women than for men, and more rapidly for girls than for boys. Conclusion: Improved identification of ADHD in adult and female patients has contributed to rapid growth in ADHD medication use. (J. of Att. Dis. 2007; 10(4) 335-342)
To evaluate which side effects of chemotherapy are considered most burdensome by patients with cancer, identify which health care professionals pay most attention to symptoms associated with ...chemotherapy-induced myelosuppression (CIM) from the patient perspective, and capture the "patient voice" describing how CIM impacts their daily lives.
Online survey of participants with breast, lung, or colorectal cancer who had received chemotherapy within the past 12 months and experienced ≥1 episode of CIM in the past year. Participants were asked to answer close-ended questions and provide qualitative responses to: "In your own words, please describe how side effects from myelosuppression have impacted your life."
Among 301 survey participants, fatigue was the most frequently reported side effect of chemotherapy; 55% of participants rated fatigue as highly bothersome (9 or 10 on a 1-10 scale of "bothersomeness"). Participants rated symptoms associated with CIM, including fatigue, weakened immune system (infections), bleeding and/or bruising, and shortness of breath, as being as bothersome as other side effects of chemotherapy, including alopecia, neuropathy, and nausea/vomiting. Overall, 24-43% of participants thought that CIM and its symptoms had a negative impact on their daily lives, including their ability to complete tasks at home and work, and to socialize. Qualitative responses supported these findings; participants highlighted that CIM-related symptoms, particularly fatigue and fear of infections, affected their ability to be physically active, complete work, or continue meaningful relationships with friends and family.
Participants described a real-world impact of CIM that often isolates them from family and friends, and means that they are unable to work or perform tasks of daily living. Using measures that help patients to recognize and communicate the signs and symptoms of CIM might increase the likelihood of maintaining daily lives as close to normal as possible, during and after chemotherapy treatment.
Characterizing genetic variants for clinical action Ramos, Erin M; Din-Lovinescu, Corina; Berg, Jonathan S ...
American journal of medical genetics. Part C, Seminars in medical genetics,
March 2014, Volume:
166C, Issue:
1
Journal Article
Open access
Genome-wide association studies, DNA sequencing studies, and other genomic studies are finding an increasing number of genetic variants associated with clinical phenotypes that may be useful in ...developing diagnostic, preventive, and treatment strategies for individual patients. However, few variants have been integrated into routine clinical practice. The reasons for this are several, but two of the most significant are limited evidence about the clinical implications of the variants and a lack of a comprehensive knowledge base that captures genetic variants, their phenotypic associations, and other pertinent phenotypic information that is openly accessible to clinical groups attempting to interpret sequencing data. As the field of medicine begins to incorporate genome-scale analysis into clinical care, approaches need to be developed for collecting and characterizing data on the clinical implications of variants, developing consensus on their actionability, and making this information available for clinical use. The National Human Genome Research Institute (NHGRI) and the Wellcome Trust thus convened a workshop to consider the processes and resources needed to: (1) identify clinically valid genetic variants; (2) decide whether they are actionable and what the action should be; and (3) provide this information for clinical use. This commentary outlines the key discussion points and recommendations from the workshop.
Comparative effectiveness research (CER) is generating intense attention as interest grows in finding new and better drug technology assessment processes. The federal government is supporting the ...expansion of CER through funding made available in the American Recovery and Reinvestment Act of 2009 (ARRA) and by establishing the Patient-Centered Outcomes Research Institute through the Patient Protection and Affordable Care Act of 2010. At the same time, personalized medicine is generating debate about its place in clinical medicine, and so, naturally, how CER can or cannot play a role in personalized medicine is part of these debates. At the heart of the debate around the role of CER in personalized medicine is the nature of personalized medicine and how it fits within contemporary clinical research concepts. We maintain in this article that CER can serve to catalyze personalized medicine, but we recognize that, for this to happen, researchers will need to embrace new data sources and new analytic approaches. We also recognize that drug technology assessment processes will have to undergo necessary adaptations to accommodate CER as configured for personalized medicine, and that clinicians will need to be educated appropriately and provided access to decision-support systems through health information technology to use the information coming from this research.
To illustrate our argument, we describe two ongoing CER studies funded and managed in the private sector evaluating personalized medicine interventions that have important clinical and financial implications. One of the studies investigates the clinical and financial effects of pharmacogenomic testing for warfarin as prescribed in conditions of typical practice settings. The other study is also set in community practice settings and compares cardiovascular outcomes of patients receiving clopidogrel who are extensive metabolizer phenotypes for the cytochrome P450
2C19
hepatic isoenzyme with all patients receiving prasugrel.
Background: Total joint arthroplasty (TJA) is one of the most common procedures performed in the United States. Outcomes of this elective procedure may be improved via preoperative optimization of ...modifiable risk factors. Purposes: We sought to summarize the literature on the clinical implications of preoperative risk factors in TJA and to develop recommendations regarding preoperative optimization of these risk factors. Methods: We searched PubMed in August 2019 with an update in September 2020 for English-language, peer-reviewed publications assessing the influence on outcomes in total hip and knee replacement of 7 preoperative risk factors—obesity, malnutrition, hypoalbuminemia, diabetes, anemia, smoking, and opioid use—and recommendations to mitigate them. Results: Sixty-nine studies were identified, including 3 randomized controlled trials, 8 prospective cohort studies, 42 retrospective studies, 6 systematic reviews, 3 narrative reviews, and 7 consensus guidelines. These studies described worse outcomes associated with these 7 risk factors, including increased rates of in-hospital complications, transfusions, periprosthetic joint infections, revisions, and deaths. Recommendations for strategies to screen and address these risk factors are provided. Conclusions: Risk factors can be optimized, with evidence suggesting the following thresholds prior to surgery: a body mass index <40 kg/m2, serum albumin ≥3.5 g/dL, hemoglobin A1C ≤7.5%, hemoglobin >12.0 g/dL in women and >13.0 g/dL in men, and smoking cessation and ≥50% decrease in opioid use by 4 weeks prior to surgery. Surgery should be delayed until these risk factors are adequately optimized.
To examine recent national trends in psychotropic use for very young children at US outpatient medical visits.
Data for 2- to 5-year-old children (N = 43 598) from the 1994-2009 National Ambulatory ...and National Hospital Ambulatory Medical Care Surveys were used to estimate the weighted percentage of visits with psychotropic prescriptions. Multivariable logistic regression was used to identify factors associated with psychotropic use. Time effects were examined in 4-year blocks (1994-1997, 1998-2001, 2002-2005, and 2006-2009).
Psychotropic prescription rates were 0.98% from 1994-1997, 0.83% from 1998-2001, 1.45% from 2002-2005, and 1.00% from 2006-2009. The likelihood of preschool psychotropic use was highest in 2002-2005 (1994-1997 adjusted odds ratio AOR versus 2002-2005: 0.67; 1998-2001 AOR versus 2002-2005: 0.63; 2006-2009 AOR versus 2002-2005: 0.64), then diminished such that the 2006-2009 probability of use did not differ from 1994-1997 or from 1998-2001. Boys (AOR versus girls: 1.64), white children (AOR versus other race: 1.42), older children (AOR for 4 to 5 vs 2 to 3 year olds: 3.87), and those lacking private insurance (AOR versus privately insured: 2.38) were more likely than children from other groups to receive psychotropic prescriptions.
Psychotropic prescription was notable for peak usage in 2002-2005 and sociodemographic disparities in use. Further study is needed to discern why psychotropic use in very young children stabilized in 2006-2009, as well as reasons for increased use in boys, white children, and those lacking private health insurance.
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