Inpatient and outpatient treatment patterns of cancer-associated thrombosis in the United States.

Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the recommended treatment options for cancer-associated thrombosis (CAT) in the 2019 National Comprehensive Care Network guidelines. Little is known about the current utilization of DOACs in CAT patients, particularly on the inpatient to outpatient therapy transition. This study assessed real-world treatment patterns of CAT in hospital/ED in adult cancer patients (≥ 18 years) diagnosed with CAT during a hospital visit in IQVIA's Hospital Charge Data Master database between July 1, 2015 and April 30, 2018, and followed their outpatient medical and pharmacy claims to evaluate the initial inpatient/ED and outpatient anticoagulants received within 3 months post-discharge. Results showed that LMWH and unfractionated heparin (UFH) were the most common initial inpatient/ED CAT treatments (35.2% and 27.4%, respectively), followed by DOACs (9.6%); 20.8% of patients received no anticoagulants. Most DOAC patients remained on DOACs from inpatient/ED to outpatient settings (71.4%), while 24.1%, 43.5%, and 0.1% of patients treated with LMWH, warfarin, or UFH respectively, remained on the same therapy after discharge. In addition, DOACs were the most common initial post-discharge outpatient therapy. Outpatient treatment persistence and adherence appeared higher in patients using DOACs or warfarin versus LMWH or UFH. This study shows that DOACs are used as an inpatient/ED treatment option for CAT, and are associated with less post-discharge treatment switching and higher persistence and adherence. Further research generating real-world evidence on the role of DOACs to help inform the complex CAT clinical treatment decisions is warranted.

Symptom report and treatment experience of hypogonadal men with and without type 2 diabetes in a United States health plan.

BACKGROUND: Although hypogonadism (HG) is interrelated with type 2 diabetes mellitus (T2DM), there is little information about men's experiences with HG, T2DM, and testosterone replacement therapy (TRT). We examined symptoms and TRT use among men with HG, with and without T2DM, who received care within a single United States health plan. METHODS: Men aged ≥ 18 years with HG, with and without T2DM, were identified from the 2008 to 2010 Reliant Medical Group electronic medical record database. Surveys responses compared by T2DM status using chi-square or Wilcoxon rank sum tests. RESULTS: A total of 93 men were included (19 with HG and T2DM, 74 with HG only). Men with both HG and T2DM were more frequently treated for their HG by an endocrinologist (52.6%), compared with men with HG only (28.4%, p = 0.058). Erectile dysfunction (ED) was the primary reason for seeking care among all surveyed men, although men with HG and T2DM reported experiencing ED more often (94.7%) than men with HG only (46.0%, p < 0.0001). Additional reasons for seeking care were similar between cohorts and included loss of energy and decreased sex drive. Most men (88.2%) reported using TRT, primarily as injection or gel formulations. Discontinuation of TRT was reported slightly more frequently by men with HG and T2DM (68.4%), compared with men with HG only (55.4%, p > 0.05). CONCLUSIONS: This study provides information about symptoms and TRT utilisation among HG men with and without T2DM. Men with HG only were less likely than those with both HG and T2DM to report that they were currently experiencing key symptoms compared with when they were first diagnosed, regardless of TRT utilisation, and were less likely to report ED as a current symptom.

Identification and diagnosis of Secondary Progressive Multiple Sclerosis during the clinical encounter: Results from a physician survey.

BACKGROUND: It is difficult to characterize the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS), due to symptomatic variability across patients. Diagnosis of SPMS is prolonged and often established retrospectively, as it is based on patient clinical history and symptoms. This cross-sectional study aimed to identify MS neurologist reported clinical indicators deemed important in diagnosing SPMS in clinical practice. METHODS: A web-based quantitative survey was conducted among MS-treating neurologists across the United States in January 2019. The questionnaire comprised of 17 questions evaluating primary clinical indicators used by neurologists in assessing patient progression to SPMS. Treatment approach and factors influencing treatment decision-making following SPMS diagnosis were also analyzed in the survey. RESULTS: Overall, 300 neurologists completed the survey; most of the respondents were general MS-treating neurologists (63%) and from private care setting (58%). The overall respondents as well as MS-focused neurologists ranked patient history (45% and 42%, respectively) and patients' neurological exam (39% and 44%, respectively) as -primary clinical indicators of SPMS diagnosis. 57% of neurologists always or mostly switched disease modifying therapies after progression to SPMS, and mostly considered 3-6 months' assessment interval to diagnose SPMS. CONCLUSION: The survey indicated that neurologists are able to recognize signs of SPMS within six months of symptomatic assessment. The diagnosis is primarily based on patient history among MS-treating neurologists. Therefore, continued education to neurologists may facilitate early diagnosis and timely introduction of effective treatment to manage the progression of SPMS.

Defining left ventricular segmental and global function by echocardiographic intraventricular contrast flow patterns.

Contrast echocardiography improves left ventricular (LV) endocardial border delineation by enhancement of the blood-tissue interface. In particular, the contrast appearing within the LV chamber exhibits characteristic flow patterns over the cardiac cycle, which may be related to the surrounding myocardial wall motion. To determine the relation between the LV intracavitary contrast flow pattern and surrounding wall motion, we reviewed the contrast-enhanced images of 348 consecutive patients studied at rest. We defined 2 different patterns of intracavitary contrast flow as visualized from apical views: a swift, vertical, and homogeneous flow towards the apex (pattern A), and a distinctly protracted, swirling, and heterogeneous flow (pattern B). Images recorded on videotapes were reviewed and the type of pattern (A or B) was determined within the initial 30 to 45 seconds of contrast appearance in the left ventricle. Contrast flow patterns interpreted by independent reviewer were then compared with the interpretation of the LV segmental and global function in each patient. Results demonstrate that 224 of 245 (91%) patients exhibiting pattern A had normal LV segmental function. Furthermore, all but 1 patient (102 of 103) with pattern B had > or =1 wall motion abnormality (p <0.0001). Contrast flow pattern B was observed irrespective of the location of LV wall motion abnormality. Global LV function was normal in 93% of patients exhibiting pattern A, whereas varying degrees of LV dysfunction were noted in 83% of patients with pattern B (p <0.0001). The presence of mitral regurgitation (p = 0.46), aortic insufficiency (p = 0.066), or mitral inflow Doppler abnormality (p = 0.102) was not significantly associated with either pattern. Thus, during contrast echocardiography, the LV intracavitary contrast flow pattern complements the assessment of global and segmental LV function.

Differential effects of 5-hydroxytryptaminergic antagonists upon apomorphine- and lergotrile-induced hypothermia and stereotyped behaviour in rats.

The dopaminergic stimulants apomorphine and lergotrile both evoked hypothermia and stereotyped behaviour in rats. These drug effects were sensitive to antagonism by haloperidol, a dopaminergic receptor blocker. In rats pretreated with 5-hydroxytryptaminergic receptor blockers, cinanserin reduced apomorphine-induced hypothermia but cyproheptadine did not. Both cinanserin and cyproheptadine significantly potentiated lergotrile-induced hypothermia. Similarly, the stereotypic effects of apomorphine were partly reduced by cyproheptadine, although higher doses of cyproheptadine did potentiate lergotrile-induced stereotyped behaviour. These findings of different influences of 5-HT antagonists upon the effects of apomorphine and lergotrile indicate that these two dopaminergic stimulants may not work in identical manner to produce outwardly similar drug effects.

Ethylene oxide: evidence of human chromosomal effects.

Ethylene oxide is a known mutagen as indicated by short-term testing in vitro and in vivo. Occupational exposure can occur during ethylene oxide gas sterilization of materials for hospital and other use. To study the problem in a hospital sterilization facility where occupational exposure was suspected, epidemiologic, analytic and bioassay tools were employed. All persons whose work activities involved some aspect of the sterilization process were considered exposed to the gas. Within this group of symptomatic and asymptomatic individuals, chronic and incidental exposure was documented by clinical history. Sister chromatid exchanges were studied in lymphocytes cultured from exposed individuals as well as comparable controls. Four chronically exposed persons who reported upper respiratory and neurologic symptoms were studied in some detail. This group showed significantly increased sister chromatid exchange at three weeks and again at eight weeks after the last known exposure. Another group of eight persons with fewer complaints studied as late as the ninth week showed significantly increased exchanges. Incidental exposure may also increase sister chromatid exchange. The measured maximum concentration of ethylene oxide in the sterilizer room was 36 ppm (within standards set by the Occupational Safety and Health Administration).

An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17alpha-hydroxylase, C17-20 lyase.

Ovarian theca/interstitial cells produce androgens in response to luteinizing hormone (LH) stimulation and apolipoprotein (apo) E exerts a selective effect on the type of steroid product made by these cells. We have identified an apoE synthetic peptide containing the low density lipoprotein (LDL) receptor binding domain, acetyl-Y(LRK LRKRLLRDADDL)2C, that mimics the activity of native apoE. Depending on the concentration, the apoE synthetic peptide either enhanced or inhibited the LH-stimulated production of androstenedione with concomitant changes in the mRNA for its synthetic enzyme, P450 17alpha-hydroxylase, C17-20 lyase, without any changes in progesterone production or the mRNA for its synthetic enzyme, P450 cholesterol side-chain cleavage. The apoE synthetic peptide caused changes in the rate of transcription of the mRNA for P450 17alpha-hydroxylase, C17-20 lyase without altering its stability. Pretreatment of the theca/interstitial cells with receptor-associated protein, which blocks apoE binding to members of the LDL receptor superfamily, prevented the apoE synthetic peptide-mediated stimulation of androstenedione and mRNA for P450 17alpha-hydroxylase, C17-20 lyase, but did not attenuate the inhibitory activity of the peptide. Thus, apolipoprotein E selectively altered the type of steroid made by ovarian theca/interstitial cells by regulating the transcription of mRNA for the gene for P450 17alpha-hydroxylase, C17-20 lyase, in part through its interaction with apolipoprotein E-specific receptors of the LDL receptor superfamily.

Membrane-associated cathepsin L: a role in metastasis of melanomas.

Subcellular distribution of cathepsin L, the major protein released by transformed or ras transfected fibroblasts, was examined in murine liver, murine B16 amelanotic melanoma and human A2058 melanoma after sequential differential and Percoll density gradient centrifugation. In both murine and human melanomas, cathepsin L activity was found to be enriched in plasma membrane fractions; cathepsin L in these fractions was in both native and acid activatable forms. Plasma membrane fractions from B16 melanoma subpopulations of "low" and "high" metastatic potential were assayed for activity of cathepsin L and of heat stable endogenous inhibitors. The relative specific activity of cathepsin L was 7-fold greater in the subpopulation of "high" metastatic potential, whereas cysteine proteinase inhibitory activity was 5-fold less. Since cathepsin L can degrade intact basement membrane, this membrane-associated cathepsin L may well contribute to metastatic spread of melanomas.

Two fatalities after acute occupational exposure to ethylene dibromide.

A worker collapsed while working inside a tank that was later found to contain residues of ethylene dibromide. He died 12 hours later with metabolic acidosis, depression of the CNS, and laboratory evidence of liver damage. A supervisor attempting to rescue the first victim also collapsed inside the tank and died 64 hours later with intractable metabolic acidosis and hepatic and renal failure. The clinical, pathological, and toxicological findings, as well as results of industrial hygiene sampling, are reported. Pathophysiological mechanisms and possible therapeutic interventions are discussed. The cases demonstrate the extreme hazards of exposure to the highly toxic chemical. The importance of protective work practices wherever there is potential exposure to ethylene dibromide is emphasized.