A randomized study of solriamfetol for excessive sleepiness in narcolepsy

Objective: Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. This phase 3 study (NCT02348593) evaluated the safety and efficacy of solriamfetol in narcolepsy. Methods: Patients with narcolepsy with mean sleep latency <25 minutes on the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS) score ≥10, and usual nightly sleep ≥6 hours were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Coprimary endpoints were change from baseline to week 12 in MWT and ESS. Improvement on the Patient Global Impression of Change (PGI-C) was the key secondary endpoint. Results: Safety and modified intention-to-treat populations included 236 and 231 patients, respectively. Solriamfetol 300 and 150 mg were positive on both coprimary endpoints. Least squares mean (standard error [SE]) changes from baseline were 12.3 (SE = 1.4) and 9.8 (SE = 1.3) minutes for solriamfetol 300 and 150 mg on the MWT, respectively, versus 2.1 (SE = 1.3) minutes for placebo, and −6.4 (SE = 0.7) for 300 mg and −5.4 (SE = 0.7) for 150 mg on the ESS versus −1.6 (SE = 0.7) for placebo (all p < 0.0001). At week 12, higher percentages of patients treated with solriamfetol 150 mg (78.2%) and 300 mg (84.7%) reported PGI-C improvement relative to placebo (39.7%; both p < 0.0001). Adverse events ≥5% across all solriamfetol doses included headache (21.5%), nausea (10.7%), decreased appetite (10.7%), nasopharyngitis (9.0%), dry mouth (7.3%), and anxiety (5.1%). Interpretation: Solriamfetol has the potential to be an important therapeutic option for the treatment of impaired wakefulness and excessive sleepiness in patients with narcolepsy. ANN NEUROL 2019;85:359–370

Occurrence of medical co-morbidity in mild cognitive impairment: implications for generalisation of MCI research

Background: diagnosis of mild cognitive impairment (MCI) typically excludes individuals with medical co-morbidity. Interest in MCI screening raises the questions of what are the best criteria to identify a representative sample and what factors are associated with MCI progression to dementia

Analysis of the Association between Metabolic Syndrome and Disease in a Workplace Population over Time

Objectives:  While research has confirmed an association between metabolic syndrome (MetS) and diseases such as heart disease and diabetes, none of these studies have been conducted in a worksite population. Because corporations are often the primary payer of health-care costs in the United States, they have a vested interest in identifying the magnitude of MetS risk factors in employed populations, and also in knowing if those risk factors are associated with other health risks or medical conditions. Methods:  This study identified the prevalence of MetS risk factors and self-reported disease in employees (N = 3285) of a manufacturing corporation who participated in a health risk appraisal and biometric screening in both 2004 and 2006. Health-care costs, pharmacy costs, and short-term disability costs were compared for those with and without MetS and disease. Results:  The prevalence of MetS increased from 2004 to 2006 in this employed population. Those with MetS were significantly more likely to self-report arthritis, chronic pain, diabetes, heartburn, heart disease, and stroke. Employees with MetS in 2004 were also significantly more likely to report new cases of arthritis, chronic pain, diabetes, and heart disease in 2006. The costs of those with MetS and disease were 3.66 times greater than those without MetS and without disease. Conclusions:  MetS is associated with disease and increased costs in this working population. There is an opportunity for health promotion to prevent MetS risk factors from progressing to disease status which may improve vitality for employees, as well as limit the economic impact to the corporation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75375/1/j.1524-4733.2009.00651.x.pd

Exploring dietitians' salient beliefs about shared decision-making behaviors

<p>Abstract</p> <p>Background</p> <p>Shared decision making (SDM), a process by which health professionals and patients go through the decision-making process together to agree on treatment, is a promising strategy for promoting diet-related decisions that are informed and value based and to which patients adhere well. The objective of the present study was to identify dietitians' salient beliefs regarding their exercise of two behaviors during the clinical encounter, both of which have been deemed essential for SDM to take place: (1) presenting patients with all dietary treatment options for a given health condition and (2) helping patients clarify their values and preferences regarding the options.</p> <p>Methods</p> <p>Twenty-one dietitians were allocated to four focus groups. Facilitators conducted the focus groups using a semistructured interview guide based on the Theory of Planned Behavior. Discussions were audiotaped, transcribed verbatim, coded, and analyzed with NVivo8 (QSR International, Cambridge, MA) software.</p> <p>Results</p> <p>Most participants stated that better patient adherence to treatment was an advantage of adopting the two SDM behaviors. Dietitians identified patients, physicians, and the multidisciplinary team as normative referents who would approve or disapprove of their adoption of the SDM behaviors. The most often reported barriers and facilitators for the behaviors concerned patients' characteristics, patients' clinical situation, and time.</p> <p>Conclusions</p> <p>The implementation of SDM in nutrition clinical practice can be guided by addressing dietitians' salient beliefs. Identifying these beliefs also provides the theoretical framework needed for developing a quantitative survey questionnaire to further study the determinants of dietitians' adoption of SDM behaviors.</p

Changes in practice patterns affecting in-hospital and post-discharge survival among ACS patients

BACKGROUND: Adherence to clinical practice guidelines for the treatment of specific illnesses may result in unexpected outcomes, given that multiple therapies must often be given to patients with diverse medical conditions. Yet, few studies have presented empirical evidence that quality improvement (QI) programs both change practice by improving adherence to guidelines and improve patient outcomes under the conditions of actual practice. Thus, we focus on patient survival, following hospitalization for acute coronary syndrome in three successive patient cohorts from the same community hospitals, with a quality improvement intervention occurring between cohorts two and three. METHODS: This study is a comparison of three historical cohorts of Acute Coronary Syndrome (ACS) patients in the same five community hospitals in 1994–5, 1997, 2002–3. A quality improvement project, the Guidelines Applied to Practice (GAP), was implemented in these hospitals in 2001. Study participants were recruited from community hospitals located in two Michigan communities during three separate time periods. The cohorts comprise (1) patients enrolled between December 1993 and April 1995 (N = 814), (2) patients enrolled between February 1997 and September 1997 (N = 452), and (3) patients enrolled between January 14, 2002 and April 13, 2003 (N = 710). Mortality data were obtained from Michigan's Bureau of Vital Statistics for all three patient cohorts. Predictor variables, obtained from medical record reviews, included demographic information, indicators of disease severity (ejection fraction), co-morbid conditions, hospital treatment information concerning most invasive procedures and the use of ace-inhibitors, beta-blockers and aspirin in the hospital and as discharge recommendations. RESULTS: Adjusted in-hospital mortality showed a marked improvement with a HR = 0.16 (p < 0.001) comparing 2003 patients in the same hospitals to those 10 years earlier. Large gains in the in-hospital mortality were maintained based on 1-year mortality rates after hospital discharge. CONCLUSION: Changes in practice patterns that follow recommended guidelines can significantly improve care for ACS patients. In-hospital mortality gains were maintained in the year following discharge

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection