Risk of mortality and second malignancies in primary myelofibrosis before and after ruxolitinib approval.

BACKGROUND: Primary myelofibrosis (PMF) is associated with morbidity and mortality. Ruxolitinib gained US FDA approval for treatment of intermediate/high-risk PMF in November 2011. We evaluated differences in survival and second primary malignancy (SPM) incidence among US PMF patients in the years before and after ruxolitinib approval. METHODS: We conducted a retrospective study utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 database for PMF patients. We divided patients into five-year cohorts pre- (2007-2011) and post-ruxolitinib (2012-2016) approval and compared relative survival rates (RSRs) to the standard population and standardized incidence rates (SIRs) of SPMs between cohorts. RESULTS: We included 2020 patients diagnosed with PMF from 2007-2016 in this study. There was no difference in the four-year RSRs between cohorts (54 % vs. 57 %, p = 0.776). More patients developed SPMs in the post-ruxolitinib cohort (8% vs. 6%, p = 0.041). The majority of SPMs were hematologic with higher incidence of AML transformation in the post-ruxolitinib cohort (SIR 125.29 vs. 70.55). CONCLUSIONS: PMF prognosis remains poor in the years following ruxolitinib's approval. SPM incidence including AML transformation is higher in the years after approval. Further studies are needed to determine the true impact of ruxolitnib on population outcomes.

Oncologic Services Through Project Access and Other Safety Net Care Coordination Programs.

PURPOSE: Little is known about the provision of oncologic services by Project Access safety net care coordination programs. MATERIALS AND METHODS: Information on safety net care coordination program locations, health services, and patient eligibility was obtained via program Web sites and calls. For programs not offering oncologic care, program directors were interviewed to identify oncologic care barriers. RESULTS: Web sites of 29 safety net care coordination programs in 22 states were identified; 62% (n = 18) offered oncologic services. Programs were in 65% (n = 11) of states that did not expand Medicaid. Of those offering oncologic services, 83% (n = 15) offered free chemotherapy, and 93% (n = 27) of all programs offered oncologic imaging. Program director interviews revealed costs, longitudinal care, and multiple-physician buy-in as barriers limiting oncologic care. CONCLUSION: Third-party care coordination centers provide a novel and potentially unrecognized approach to increasing oncology service access. Further research should identify strategies to overcome the relative lack of oncologic care offerings.

Traumatic Pneumoperitoneum After Vaginal Intercourse.

OBJECTIVES: Pneumoperitoneum with peritonitis, although uncommon, is a serious injury encountered in the pediatric emergency department. Although the patients may often appear ill or toxic, they can have normal vital signs at initial presentation. Patients with such injury can present with a variety of complaints because of the nature of referred pain. As a result, some patients may be more or less straightforward, thus illustrating the importance of obtaining a detailed history and performing a thorough physical examination. METHODS: We discuss an uncommon case report of pneumoperitoneum with peritonitis in an adolescent patient presenting with vaginal bleeding and abdominal pain hours after vigorous coitus. RESULTS: Examination under anesthesia, flexible sigmoidoscopy, and exploratory laparoscopy revealed a vaginal laceration and a 2- to 3-cm perforated area at the left edge of the vaginal laceration that involved the rectovaginal septum entering the peritoneal cavity. CONCLUSIONS: Pneumoperitoneum resulting from vaginal intercourse in an otherwise healthy adolescent female is a rare cause of peritonitis. Although it has been described in the adult literature, this case illustrates the importance of considering sexual history as a contributory factor in pediatric patients presenting with an acute abdomen.

The National MDS Natural History Study: design of an integrated data and sample biorepository to promote research studies in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS), a spectrum of heterogeneous hematopoietic stem cell diseases, vary in clinical severity, response to therapy, and propensity toward progression to acute myeloid leukemia. These are acquired clonal disorders resulting from somatic mutations within the hematopoietic stem or progenitor cell population. Understanding the natural history and the risk of developing leukemia and other adverse outcomes is dependent on access to well-annotated biospecimens linked to robust clinical and molecular data. To facilitate the acquisition and distribution of MDS biospecimens to the wider scientific community and support scientific discovery in this disease, the National MDS Natural History study was initiated by the National Heart, Lung, and Blood Institute (NHLBI) and is being conducted in collaboration with community hospitals and academic medical centers supported by the National Cancer Institute (NCI). The study will recruit up to 2000 MDS patients or overlapping myeloproliferative neoplasms (MDS/MPN) and up to 500 cases of idiopathic cytopenia of undetermined significance (ICUS). The National MDS Natural History Study (NCT02775383) will offer the world's largest disease-focused tissue biobank linked to longitudinal clinical and molecular data in MDS. Here, we report on the study design features and describe the vanguard phase of 200 cases. The study assembles a comprehensive clinical database, quality of life results, laboratory data, histopathology slides and images, genetic information, hematopoietic and germline tissues representing high-quality biospecimens and data from diverse centers across the United States. These resources will be available to the scientific community for investigator-initiated research.

Certified Child Life Specialists Lessen Emotional Distress of Children Undergoing Laceration Repair in the Emergency Department.

OBJECTIVE: The objective of this study is to evaluate the impact of certified child life specialists (CCLSs) on the emotional responses of children undergoing laceration repair in the emergency department (ED). METHODS: Patients 4 to 12 years of age who required laceration repair by suturing were prospectively enrolled at an urban tertiary pediatric ED. Certified child life specialists are not available at all times in our institution, allowing for a priori categorization of subjects into 2 comparison groups, those with and those without CCLS involvement. Subjects requiring anxiolysis, pharmacologic sedation, narcotics, or physical restraint were excluded. The Children's Emotional Manifestation Scale, a previously validated Likert-like tool, was used to quantify the patients' distress, with a higher score reflecting a more emotional child. Just before placement of the first suture, subjects were scored by trained independent observers. Baseline data included age, sex, race, type of local anesthetic, length and location of laceration, and analgesics administered. The primary endpoint of emotional score was compared with a 2-tailed Mann-Whitney U test, with a P < 0.05 considered statistically significant. RESULTS: Two hundred one patients constituted the final study cohort, with 103 (51%) having CCLS involvement. Study groups did not differ in regards to any baseline demographic or clinical characteristics. The median emotional score for patients with child life services was 7 (interquartile range, 6-9) versus 9 (interquartile range, 7.5-12) for those without (P < 0.0005). CONCLUSIONS: Certified child life specialist involvement is associated with less emotional distress for children undergoing laceration repair in the ED.

A methodological review of meditation research.

Despite over 50 years of research into the states of consciousness induced by various meditation practices, no clear neurophysiological signatures of these states have been found. Much of this failure can be attributed to the narrow range of variables examined in most meditation studies, with the focus being restricted to a search for correlations between neurophysiological measures and particular practices, without documenting the content and context of these practices. We contend that more meaningful results can be obtained by expanding the methodological paradigm to include multiple domains including: the cultural setting ("the place"), the life situation of the meditator ("the person"), details of the particular meditation practice ('the practice'), and the state of consciousness of the meditator ("the phenomenology"). Inclusion of variables from all these domains will improve the ability to predict the psychophysiological variables ("the psychophysiology") associated with specific meditation states and thus explore the mysteries of human consciousness.

Factors affecting costs in Medicaid populations with behavioral health disorders.

BACKGROUND: Persons with behavioral disorders incur higher healthcare costs. Although they utilize behavioral health (BH) services others do not, they also have higher utilization of medical services OBJECTIVES: : To determine the degree to which higher costs for persons with BH disorders are attributable to utilization of BH services, multiple chronic medical conditions (CMCs) or other issues specific to populations with BH disorders. RESEARCH DESIGN: Data base consisted of claims for 63,141 Medicaid beneficiaries, 49% of whom had one of 5 categories of BH disorder. Generalized linear models were used to identify relative impact of demographics, BH status, multiple CMCs and primary care access on total, behavioral, nonbehavioral, and medical/surgical costs. RESULTS: Number of CMCs was associated with significant increases in all cost categories, including behavioral costs. Presence of any BH disorder significantly influenced these same costs, including those not associated with BH care. Effect size in each cost category varied by BH group. CONCLUSIONS: BH status has a large impact on all healthcare costs, including costs of medical and other non-BH services. The number of CMCs affects BH costs independent of BH disorder. Results suggest that costs might be reduced through better integration of behavioral and medical health services.

Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors.

INTRODUCTION: Many products labeled "herbal" or "all natural" (herbal/natural) that claim to enhance sexual performance and imply use for the treatment of erectile dysfunction (ED) are marketed as over-the-counter (OTC) dietary supplements. However, adulteration with undeclared phosphodiesterase type 5 (PDE5) inhibitors appears widespread. AIM: To assess the availability, cost, origin, categorical content, and adulteration with PDE5 inhibitors of purported herbal/natural OTC dietary supplements claiming to naturally enhance sexual performance. METHODS: Pfizer Global Security coordinated sample collection (all from convenience stores and filling stations in two U.S. metropolitan areas except for seven from U.S. Customs seizures) and liquid chromatography/mass spectrometry examination. MAIN OUTCOME MEASURE: Adulteration with synthetic PDE5 inhibitors. RESULTS: Ninety-one samples labeled as 58 distinct products and priced from $2.99 to $17.99 were evaluated. Origin/manufacture was claimed as United States (n = 62), apparently Asian (n = 15), and not clearly identified (n = 14). Although no sample claimed to include synthetic substances, 74 (81%) contained PDE5-inhibitor pharmaceutical ingredients, including tadalafil and/or sildenafil (n = 40, of which 18 contained >110% of the highest approved drug product strength) or PDE5-inhibitor analogs (n = 34). Pronounced heterogeneity of contents between samples within individual products indicated minimal quality control during manufacture. Labeling was inadequate (e.g., lacking lot number and/or expiry date) for 17 products (23 samples) and inconsistent between samples within a given product (e.g., in manufacturer, lot number, and/or expiry date) for seven of 17 products having multiple samples. Only 14 samples warned against concomitant nitrate use. CONCLUSIONS: Ethical pharmaceutical companies are concerned for an unsuspecting public when their products are counterfeited, mislabeled, and illegally offered for sale in an unsafe manner. Because of the dangers of adulteration with synthetic PDE5 inhibitors, absent safety warnings, and lack of quality or consistent manufacture, men with ED unknowingly risk their health by using OTC herbal/natural products that claim to enhance sexual performance.

The C-terminal putative nuclear localization sequence of breast cancer metastasis suppressor 1, BRMS1, is necessary for metastasis suppression.

Breast cancer metastasis suppressor 1 (BRMS1) is a predominantly nuclear protein that suppresses metastasis in multiple human and murine carcinoma cell lines. BRMS1 interacts with several nuclear proteins including SIN3:HDAC chromatin remodeling complexes that are involved in repressing transcription. However, recent reports suggest BRMS1 may function in the cytoplasm. BRMS1 has two predicted nuclear localization sequences (NLS) that are located near the C-terminus (amino acids 198-205 and 238-244, NLS1 and NLS2 respectively). We hypothesized that nuclear localization sequences of BRMS1 were essential for BRMS1 mediated metastasis suppression. Replacement of NLS2 with NLS1 (BRMS1(NLS1,1)), truncation at 238 (BRMS1(ΔNLS2)), or switching the location of NLS1 and NLS2 (BRMS1(NLS2,1)) did not affect nuclear localization; but, replacement of NLS1 with NLS2 (BRMS1(NLS2,2)) or truncation at 197 (BRMS1(ΔNLS) which removes both NLS) promoted cytoplasmic localization. MDA-MB-231 human metastatic breast cancer cells transduced with BRMS1(NLS1,1), BRMS1(NLS2,2) or BRMS1(NLS2,1) were evaluated for metastasis suppression in an experimental xenograft mouse model. Interestingly, while NLS2 was not necessary for nuclear localization, it was found to be important for metastasis suppression since BRMS1(NLS2,2) suppressed metastasis by 85%. In contrast, BRMS1(NLS2,1) and BRMS1(NLS1,1) did not significantly suppress metastasis. Both BRMS1 and BRMS1(NLS2,2) co-immunoprecipitated with SIN3A in the nucleus and cytoplasm; however, BRMS1(NLS1,1) and BRMS1(NLS2,1) were associated with SIN3A in the nucleus only. Moreover, BRMS1 and BRMS1(NLS2,2), but not BRMS1(NLS1,1) and BRMS1(NLS2,1), down-regulated the pro-metastatic microRNA, miR-10b. Together, these data demonstrate an important role for NLS2 in the cytoplasm that is critical for metastasis suppression and is distinct from nuclear localization.

Contemplating cognitive enhancement in medical students and residents.

Medical school and residency can be stressful times, involving years of intensive academic study and pressure to earn high grades. Students and residents must learn to care for the sick, a task requiring long work hours and sleep deprivation. In such an environment, it is important to monitor the mental health of trainees and the factors that influence it. This essay examines a relatively unexplored facet of physician mental health: the use of pharmacological stimulants by students and residents to study better, earn higher grades, stay awake longer, and take better care of patients. Practical and ethical considerations of stimulant use in the medical profession, along with future directions for medical student mental health, are discussed.

Cell sources and support programs for stem cell research and cell-based therapy in the USA.

In August 2002, the Health & Human Services Secretary Tommy Thompson and National Institutes of Health (NIH) Director Elias Zerhouni announced the creation of a new NIH Task Force to advance stem cell research. The National Heart, Lung, and Blood Institute (NHLBI), with a long history of sponsored research programs for stem cell biology, is participating in the NIH Stem Cell Task Force to facilitate stem cell and embryonic stem (ES) cell research including programs to improve access to cell sources. Programs being implemented include infrastructure enhancement awards to develop eligible human ES cell lines into distribution-quality cell lines, grant supplements for human ES cell line research, an educational program to provide laboratory courses on human ES cell culture techniques, and a new training program to assist investigators wishing to re-direct their laboratories into stem cell research.

Transrenal arteriovenous dialysis graft creation: survival and patency in a swine model.

PURPOSE: To investigate transrenal arteriovenous graft creation in an animal model and to report survival and patency. MATERIALS AND METHODS: Arteriovenous grafts were created from the renal artery to the renal vein in 10 swine. Renal access was accomplished with a combined percutaneous and transvascular approach. A reinforced 6-mm polytetrafluoroethylene conduit was tunneled between both flank access points, and stent-grafts were deployed from each of the renal origins into the conduit. Clopidogrel (10 mg per kilogram of body weight) was administered intravenously during the procedure, followed by a daily oral dose (75 mg) for up to 2 weeks. Animals were monitored with auscultation and angiography for up to 1 month; necropsy was performed in all animals. RESULTS: Rapid arteriovenous flow at completion angiography was achieved in eight of 10 animals. Shunts were patent in five of six animals that were followed for 1 month. Diffuse pseudointimal hyperplasia was mild in three of six shunts and moderate in two (focal stenoses). Immediate thrombosis occurred in the first two animals when the clopidogrel bolus was administered after stent-graft deployment. These shunts were recanalized mechanically. Shunts were immediately patent in five of the six remaining shunts when the clopidogrel bolus was administered prior to stent-graft deployment. Complications occurred in four of 10 animals, three of which were euthanized within 1 week. The bowel was traversed in two animals, and renal vein laceration occurred during two procedures because of failure of the stent-graft delivery system. CONCLUSION: Transrenal arteriovenous graft creation in swine is technically feasible, and long-term patency is possible with antiplatelet therapy.