Integration and evaluation of chest X-ray artificial intelligence in clinical practice.

Purpose: To integrate and evaluate an artificial intelligence (AI) system that assists in checking endotracheal tube (ETT) placement on chest x-rays (CXRs) in clinical practice. Approach: In clinical use over 17 months, 214 CXR images were ordered to check ETT placement with AI assistance by intensive care unit (ICU) physicians. The system was built on the SimpleMind Cognitive AI platform and integrated into a clinical workflow. It automatically identified the ETT and checked its placement relative to the trachea and carina. The ETT overlay and misplacement alert messages generated by the AI system were compared with radiology reports as the reference. A survey study was also conducted to evaluate usefulness of the AI system in clinical practice. Results: The alert messages indicating that either the ETT was misplaced or not detected had a positive predictive value of 42% (21/50) and negative predictive value of 98% (161/164) based on the radiology reports. In the survey, radiologist and ICU physician users indicated that they agreed with the AI outputs and that they were useful. Conclusions: The AI system performance in real-world clinical use was comparable to that seen in previous experiments. Based on this and physician survey results, the system can be deployed more widely at our institution, using insights gained from this evaluation to make further algorithm improvements and quality assurance of the AI system.

Early Opportunities to Explore Occupational Identity Change: Qualitative Study of Return-To-Work Experiences After Stroke.

BACKGROUND: Rates of return-to-work after stroke are low, yet work is known to positively impact people's wellbeing and overall health outcomes. OBJECTIVE: To understand return-to-work trajectories, barriers encountered, and resources that may be used to better support participants during early recovery and rehabilitation. PARTICIPANTS: The experiences of 31 participants (aged 25-76 years) who had or had not returned to work after stroke were explored. METHODS: Interview data were analysed using reflexive thematic analysis methods within a broader realist research approach. RESULTS: Participants identified an early need to explore a changed and changing occupational identity within a range of affirming environments, thereby ascertaining their return-to-work options early after stroke. The results articulate resources participants identified as most important for their occupational explorations. Theme 1 provides an overview of opportunities participants found helpful when exploring work options, while theme 2 explores fundamental principles for ensuring the provided opportunities were perceived as beneficial. Finally, theme 3 provides an overview of prioritized return-to-work service characteristics. CONCLUSION: The range and severity of impairments experienced by people following stroke are broad, and therefore their return-to-work needs are diverse. However, all participants, irrespective of impairment, highlighted the need for early opportunities to explore their changed and changing occupational identity.

Predictors of Invasiveness in Adenocarcinoma of Lung with Lepidic Growth Pattern.

Lung adenocarcinoma with lepidic growth pattern (LPA) is characterized by tumor cell proliferation along intact alveolar walls, and further classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive lepidic predominant adenocarcinoma (iLPA). Accurate diagnosis of lepidic lesions is critical for appropriate prognostication and management as five-year survival in patients with iLPA is lower than in those with AIS and MIA. We aimed to evaluate the accuracy of CT-guided core needle lung biopsy classifying LPA lesions and identify clinical and radiologic predictors of invasive disease in biopsied lesions. Thirty-four cases of adenocarcinoma with non-invasive lepidic growth pattern on core biopsy pathology that subsequently were resected between 2011 and 2018 were identified. Invasive LPA vs. non-invasive LPA (AIS or MIA) was defined based on explant pathology. Histopathology of core biopsy and resected tumor specimens was compared for concordance, and clinical, radiologic and pathologic variables were analyzed to assess for correlation with invasive disease. The majority of explanted tumors (70.6%) revealed invasive disease. Asian race (p = 0.03), history of extrathoracic malignancy (p = 0.02) and absence of smoking history (p = 0.03) were associated with invasive disease. CT-measured tumor size was not associated with invasiveness (p = 0.15). CT appearance of density (p = 0.61), shape (p = 0.78), and margin (p = 0.24) did not demonstrate a significant difference between the two subgroups. Invasiveness of tumors with lepidic growth patterns can be underestimated on transthoracic core needle biopsies. Asian race, absence of smoking, and history of extrathoracic malignancy were associated with invasive disease.

Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1.

BACKGROUND: A number of prostaglandins (PGs) sensitize dorsal root ganglion (DRG) neurons and contribute to inflammatory hyperalgesia by signaling through specific G protein-coupled receptors (GPCRs). One mechanism whereby PGs sensitize these neurons is through modulation of "thermoTRPs," a subset of ion channels activated by temperature belonging to the Transient Receptor Potential ion channel superfamily. Acrid, electrophilic chemicals including cinnamaldehyde (CA) and allyl isothiocyanate (AITC), derivatives of cinnamon and mustard oil respectively, activate thermoTRP member TRPA1 via direct modification of channel cysteine residues. RESULTS: Our search for endogenous chemical activators utilizing a bioactive lipid library screen identified a cyclopentane PGD2 metabolite, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), as a TRPA1 agonist. Similar to CA and AITC, this electrophilic molecule is known to modify cysteines of cellular target proteins. Electophysiological recordings verified that 15d-PGJ2 specifically activates TRPA1 and not TRPV1 or TRPM8 (thermoTRPs also enriched in DRG). Accordingly, we identified a population of mouse DRG neurons responsive to 15d-PGJ2 and AITC that is absent in cultures derived from TRPA1 knockout mice. The irritant molecules that activate TRPA1 evoke nociceptive responses. However, 15d-PGJ2 has not been correlated with painful sensations; rather, it is considered to mediate anti-inflammatory processes via binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma). Our in vivo studies revealed that 15d-PGJ2 induced acute nociceptive responses when administered cutaneously. Moreover, mice deficient in the TRPA1 channel failed to exhibit such behaviors. CONCLUSION: In conclusion, we show that 15d-PGJ2 induces acute nociception when administered cutaneously and does so via a TRPA1-specific mechanism.

Random control clinical trial on the effects of aerobic exercise training on erythrocyte levels during radiation treatment for breast cancer.

BACKGROUND: Erythrocyte changes from aerobic exercise training were examined during radiation treatment of breast cancer. METHODS: Twenty sedentary females with breast carcinoma who were ages 35 to 65 years were randomized to aerobic exercise (AE) of walking for 20 to 45 minutes, 3 to 5 times per week, at 50% to 70% of measured maximum heart rates or to placebo stretching (PS) activities 3 to 5 days per week during 7 weeks of radiation treatment. Measures were obtained 1 week before and after the radiation regimen. Serum blood analyses, through complete blood counts, measured red blood cell counts (RBC), hematocrit (HCT), and hemoglobin (HB). Peak aerobic capacity (peak VO(2)) was measured by exercise testing with oxygen uptake analysis to assess training. A Wilcoxon Mann-Whitney U test examined changes between groups (P < or = .05 for significance). RESULTS: AE peak VO(2) increased by 6.3% (P = .001) and PS decreased by 4.6% (P = .083). RBC increased in AE from 4.10 to 4.21 million cells/microL and declined in PS from 4.30 to 4.19 million cells/microL; the between-group differences were significant (P = .014). HCT increased in AE from 38.0% to 38.8% and declined in PS from 37.40% to 36.50%; the between-group differences were significant (P = .046). HB increased in AE from 12.3 to 12.4 g/dL and declined in PS from 12.25 to 11.77 g/dL; the between-group differences were significant (P = .009). CONCLUSIONS: The results of the current study suggest that moderate intensity aerobic exercise appears to maintain erythrocyte levels during radiation treatment of breast cancer compared with the declines observed in nontraining individuals. These findings suggest a safe, economical method to improve fitness and maintain erythrocytes in women during radiation treatment of breast cancer.

Hypersomnias of central origin.

Hypersomnia related to CNS disorders can be due to a variety of conditions. In this review, we discuss the diagnosis and treatment of narcolepsy with and without cataplexy, idiopathic hypersomnia, recurrent hypersomnia, and related illnesses. Research has provided insight into the underlying etiologies of these disorders, such as the genetic influences on disease development and the fundamental role of hypocretins in narcolepsy. We define the current utility of diagnostic testing, including sleep studies, neuroimaging techniques, and laboratory investigations. New treatment options for hypersomnia are discussed.

Kearns-Sayre syndrome: a case report and review of cardiovascular complications.

Kearns-Sayre syndrome (KSS) is a rare genetic abnormality. Classified as a mitochondrial cytopathy, the primary pathology of this syndrome is a disturbance of mitochondrial DNA, which codes for the proteins required for the respiratory chain reaction. Onset occurs before age 20, and is manifest as chronic progressive external ophthalmoplegia and retinal degeneration. Management issues of KSS include prophylactic cardiac pacing for conduction defects, which has been shown to improve survival. Other clinical considerations relate to dietary supplements to attempt to control the progressive effects of the disease.

Phospholipid-stabilized nanoparticles of cyclosporine A by rapid expansion from supercritical to aqueous solution.

The purpose of this research was to form stable suspensions of submicron particles of cyclosporine A, a water-insoluble drug, by rapid expansion from supercritical to aqueous solution (RESAS). A solution of cyclosporine A in CO2 was expanded into an aqueous solution containing phospholipid vesicles mixed with nonionic surfactants to provide stabilization against particle growth resulting from collisions in the expanding jet. The products were evaluated by measuring drug loading with high performance liquid chromatography (HPLC), particle sizing by dynamic light scattering (DLS), and particle morphology by transmission electron microscopy (TEM) and x-ray diffraction. The ability of the surfactant molecules to orient at the surface of the particles and provide steric stabilization could be manipulated by changing process variables including temperature and suspension concentration. Suspensions with high payloads (up to 54 mg/mL) could be achieved with a mean diameter of 500 nm and particle size distribution ranging from 40 to 920 nm. This size range is several hundred nanometers smaller than that produced by RESAS for particles stabilized by Tween 80 alone. The high drug payloads (approximately 10 times greater than the equilibrium solubility), the small particle sizes, and the long-term stability make this process attractive for development.

Investigation of processing parameters of spray freezing into liquid to prepare polyethylene glycol polymeric particles for drug delivery.

The objective of this study was to investigate the influence of processing parameters on the morphology, porosity, and crystallinity of polymeric polyethylene glycol (PEG) microparticles by spray freezing into liquid (SFL), a new particle engineering technology. Processing parameters investigated were the viscosity and flow rate of the polymer solution, nozzle diameter, spray time, pressure, temperature, and flow rate of the cryogenic liquid. By varying the processing parameters and feed composition, atomization and heat transfer mechanisms were modified resulting in particles of different size distribution, shape, morphology, density, porosity, and crystallinity. Median particle diameter (M50) varied from 25 microm to 600 microm. Particle shape was spherical or elongated with highly irregular surfaces. Granule density was between 0.5 and 1.5 g/mL. In addition to producing particles of pure polymer, drug particles were encapsulated in polymeric microparticles. The encapsulation efficiency of albuterol sulfate was 96.0% with a drug loading of 2.4%, indicating that SFL is useful for producing polymeric microparticles for drug delivery applications. It was determined that the physicochemical characteristics of model polymeric microparticles composed of PEG could be modified for use as a drug delivery carrier.

Enhanced aqueous dissolution of a poorly water soluble drug by novel particle engineering technology: spray-freezing into liquid with atmospheric freeze-drying.

PURPOSE: The purpose of this work was to investigate spray-freezing into liquid (SFL) and atmospheric freeze-drying (ATMFD) as industrial processes for producing micronized SFL powders with enhanced aqueous dissolution. Micronized SFL powders dried by ATMFD were compared with vacuum freeze-dried SFL powders. METHOD: Danazol was formulated with polyvinyl alcohol (MW 22,000), polyvinylpyrrolidone K-15, and poloxamer 407 to produce micronized SFL powders that were freeze-dried under vacuum or dried by ATMFD. The powders were characterized using Karl-Fischer titration, gas chromatography, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, surface area, and dissolution testing (SLS 0.75%/Tris 1.21% buffer media). RESULTS: Micronized SFL powders containing amorphous drug were successfully dried using the ATMFD process. Micronized SFL powders contained less than 5% w/w and 50 ppm of residual water and organic solvent, respectively, which were similar to those contents detected in a co-ground physical mixture of similar composition. Micronized SFL powders dried by ATMFD had lower surface areas than powders produced by vacuum freeze-drying (5.7 vs. 8.9 m2/g) but significantly greater surface areas than the micronized bulk drug (0.5 m2/g) and co-ground physical mixture (1.9 m2/g). Rapid wetting and dissolution occurred when the SFL powders were introduced into the dissolution media. By 5 min, 100% dissolution of danazol from the ATMFD-micronized SFL powder had occurred, which was similar to the dissolution profile of the vacuum freeze-dried SFL powder. CONCLUSIONS: Vacuum freeze-drying is not a preferred technique in the pharmaceutical industry because of scalability and high-cost concerns. The ATMFD process enables commercialization of the SFL particle-engineering technology as a micronization method to enhance dissolution of hydrophobic drugs.

A novel particle engineering technology to enhance dissolution of poorly water soluble drugs: spray-freezing into liquid.

A novel cryogenic spray-freezing into liquid (SFL) process was developed to produce microparticulate powders consisting of an active pharmaceutical ingredient (API) molecularly embedded within a pharmaceutical excipient matrix. In the SFL process, a feed solution containing the API was atomized beneath the surface of a cryogenic liquid such that the liquid-liquid impingement between the feed and cryogenic liquids resulted in intense atomization into microdroplets, which were frozen instantaneously into microparticles. The SFL micronized powder was obtained following lyophilization of the frozen microparticles. The objective of this study was to develop a particle engineering technology to produce micronized powders of the hydrophobic drug, danazol, complexed with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and to compare these SFL micronized powders to inclusion complex powders produced from other techniques, such as co-grinding of dry powder mixtures and lyophilization of bulk solutions. Danazol and HPbetaCD were dissolved in a water/tetrahydrofuran cosolvent mixture prior to SFL processing or slow freezing. Identical quantities of the API and HPbetaCD used in the solutions were co-ground in a mortar and pestle and blended to produce a co-ground physical mixture for comparison. The powder samples were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), Fourier transform infrared spectrometry (FTIR), scanning electron microscopy, surface area analysis, and dissolution testing. The results provided by DSC, XRD, and FTIR suggested the formation of inclusion complexes by both slow-freezing and SFL. However, the specific surface area was significantly higher for the latter. Dissolution results suggested that equilibration of the danazol/HPbetaCD solution prior to SFL processing was required to produce the most soluble conformation of the resulting inclusion complex following SFL. SFL micronized powders exhibited better dissolution profiles than the slowly frozen aggregate powder. Results indicated that micronized SFL inclusion complex powders dissolved faster in aqueous dissolution media than inclusion complexes formed by conventional techniques due to higher surface areas and stabilized inclusion complexes obtained by ultra-rapid freezing.

Preparation of cyclosporine A nanoparticles by evaporative precipitation into aqueous solution.

Amorphous nanoparticle suspensions of a poorly water-soluble drug, cyclosporine A, are produced by a new process, evaporative precipitation into aqueous solution (EPAS). The rapid evaporation of a heated organic solution of the drug, which is atomized into an aqueous solution, results in fast nucleation leading to nanoparticles suspensions. Hydrophilic stabilizers, introduced in the organic or aqueous phases, limit particle growth and inhibit crystallization for drug concentrations as high as 35 mg/ml, and drug/surfactant ratios up to 1.0. The suspensions may be used in parenteral formulations to enhance bioavailability or may be dried to produce oral dosage forms with the potential for high dissolution rates due to the low crystallinity, small particle size and hydrophilic stabilizer that enhances wetting.