Solriamfetol for the Management of Excessive Daytime Sleepiness.

OBJECTIVE: To review efficacy, safety, and place in therapy of solriamfetol for management of excessive daytime sleepiness (EDS) in patients with narcolepsy and obstructive sleep apnea (OSA). METHODS: PubMed (1966 to January 2021) was searched using the terms solriamfetol, JZP-110, ADX-N05 and Sunosi. Human studies published in peer-reviewed medical journals in English language were reviewed. RESULTS: The efficacy and safety of solriamfetol has been reported in 2 phase II trials and 4 phase III trials (TONES 2, TONES 3, TONES 4, and TONES 5). Statistically significant improvements in the maintenance of wakefulness test were reported with solriamfetol 150 mg and 300 mg vs placebo in participants with narcolepsy (7.65- to 10.14-minute difference from placebo). In subjects with OSA, statistically significant improvements in maintenance of wakefulness test difference from placebo were also observed in those taking solriamfetol 75 mg, 150 mg, or 300 mg vs placebo (4.5- to 12.8-minute difference from placebo). Statistically significant reductions in Epworth Sleepiness Scale scores were also reported in phase III trials in subjects with narcolepsy or OSA taking solriamfetol vs placebo (ranging from - 4.7 to - 1.9 difference from placebo). Common adverse events in reported in phase III trials were headache, nausea, decreased appetite, anxiety, dry mouth, and diarrhea. Solriamfetol appears to have a reduced risk for drug interactions and fewer adverse effects compared to other agents available for management of EDS in patients with narcolepsy and OSA. CONCLUSIONS: Solriamfetol is an effective option for management of EDS in patients with narcolepsy and OSA.

PHYSICIAN ADVISERS ADD UP FOR SOME HOSPITALS.

A team of health care experts crunches the numbers sand reaches the conclusion that creating - or expanding - a physician adviser program is a good return on investment for any organization that's considering it.

Failure of the Volume Function in Granular Statistical Mechanics and an Alternative Formulation.

We first show that the currently accepted statistical mechanics for granular matter is flawed. The reason is that it is based on the volume function, which depends only on a minute fraction of all the structural degrees of freedom and is unaffected by most of the configurational microstates. Consequently, the commonly used partition function underestimates the entropy severely. We then propose a new formulation, replacing the volume function with a connectivity function that depends on all the structural degrees of freedom and accounts correctly for the entire entropy. We discuss the advantages of the new formalism and derive explicit results for two- and three-dimensional systems. We test the formalism by calculating the entropy of an experimental two-dimensional system, as a function of system size, and showing that it is an extensive variable.

Interdependence of the volume and stress ensembles and equipartition in statistical mechanics of granular systems.

We discuss the statistical mechanics of granular matter and derive several significant results. First, we show that, contrary to common belief, the volume and stress ensembles are interdependent, necessitating the use of both. We use the combined ensemble to calculate explicitly expectation values of structural and stress-related quantities for two-dimensional systems. We thence demonstrate that structural properties may depend on the angoricity tensor and that stress-based quantities may depend on the compactivity. This calls into question previous statistical mechanical analyses of static granular systems and related derivations of expectation values. Second, we establish the existence of an intriguing equipartition principle-the total volume is shared equally amongst both structural and stress-related degrees of freedom. Third, we derive an expression for the compactivity that makes it possible to quantify it from macroscopic measurements.

European guidelines for quality assurance in cervical histopathology.

The current paper presents Chapter 5 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening, which deals with the histopathological diagnosis of lesions of the uterine cervix. It completes a series of publications in journals containing the contents of other parts of the European Guidelines. Histopathology provides the final diagnosis on the basis of which treatment is planned, and serves as the gold standard for quality control of cytology and colposcopy. It is also the source of the diagnostic data stored at the cancer registry and used for evaluation of screening programmes. It is therefore important that histopathology standards are monitored and based on agreed diagnostic criteria. Histology is required to diagnose the degree of abnormality in women with persistent low-grade abnormalities including HPV-lesions, as well as high-grade lesions. Cytology may also suggest either glandular abnormalities or be suggestive of high-grade CIN, AIS or invasive cancer. Histopathologists should be aware of, and familiar with, the nature of cytological changes which may be relevant to their reports. The accuracy of the histopathological diagnosis of tissue specimens depends on adequate samples, obtained by colposcopically directed punch biopsies (with endocervical curettage if necessary) or excision of the transformation zone or conisation. An accurate histological diagnosis further depends on appropriate macroscopic description, technical processing, microscopic interpretation and quality management correlating cytological and histological diagnosis. This paper proposes guidelines for sampling and processing of cervical tissue specimens obtained by biopsy, excision and/or curettage.

Cervical screening in women over the age of 50: results of a population-based multicentre study.

OBJECTIVE: It has been suggested that women over 50 with a satisfactory negative smear history are at low risk for dyskaryosis and might be suitable for withdrawal from the cervical screening programme. The objectives of this study are to document the pattern of dyskaryosis in the cervical smears of women over 50 and to relate the risk of dyskaryosis in these women to the prior smear history. DESIGN: Available computerised smear data were analysed. SETTING: Five regions in England and Scotland; Aberdeen, Dundee, Birmingham, Gateshead and Nottingham. POPULATION: All women aged 50 or over who had a satisfactory smear between 1988 and 1996. METHODS: Smear results were sorted into individual smear records. The first smear after the age of 50 was identified as well as all smears before and after the age of 50. MAIN OUTCOME MEASUREMENTS: The smear history before and after the age of 50 was determined for all women. The relative risk of dyskaryosis as well as the time to dyskaryosis was calculated for women whose raw data were available. RESULTS: The study included 170,436 women with at least one satisfactory smear after 50. No results of previous smears were available in 90,546 (54%) of women but 36,512 (21%) of women had a satisfactory negative smear history. Women with prior dyskaryosis or borderline nuclear abnormalities (BNA) had an increased risk of dyskaryosis after the age of 50 compared with women with a negative history (RR 4.39 and 3.08 respectively). It was notable that 1.8% of women with a negative history still demonstrated subsequent dyskaryosis. CONCLUSIONS: Women with either dyskaryosis or BNA before 50 are not suitable for withdrawal from cervical screening. Well-screened women with a negative smear history at the age 50 still have a residual risk of subsequently developing a new abnormality.