Genomic and Phenotypic Safety Assessment of Probiotic Bacillus coagulans Strain JBI-YZ6.3.

Spore-forming Bacillus coagulans has been widely recognized as an important probiotic, which is commonly used in products for human consumption and animal feeds. B. coagulans exhibits beneficial traits from both Bacillus and lactic acid-producing Lactobacillus. The present study evaluated the safety of the newly isolated B. coagulans strain JBI-YZ6.3, using combined genomic and phenotypic analysis approaches. The taxonomic classification based on genome sequence and biochemical tests identified strain JBI-YZ6.3 as B. coagulans. Comprehensive genome-based analyses established JBI-YZ6.3 as a novel strain of B. coagulans. Antibiotic susceptibility testing showed that the strain JBI-YZ6.3 was sensitive to a panel of fourteen antibiotics, and no genes related to antibiotic resistance were found in its genome. The spores of strain JBI-YZ6.3 exhibited tolerance to acid and bile salts, as well as stability at ambient and elevated conditions of temperature and relative humidity. There were no homologs of Bacillus toxin genes identified in the genome of JBI-YZ6.3, and the strain exhibited no cytotoxicity towards Vero cells and human peripheral blood mononuclear cells. In conclusion, findings from this study support the safety of B. coagulans strain JBI-YZ6.3, which can be developed into new probiotic products for preventive and therapeutic benefits in human and animal hosts.

Complete Genomic Sequence of Bacillus coagulans Strain JBI-YZ6.3: a Natural Spore-Forming Isolate from Food-Grade Tapioca Starch.

Bacillus coagulans strain JBI-YZ6.3 is a safe probiotic bacterium isolated from food-grade tapioca starch. The complete genome of B. coagulans JBI-YZ6.3 comprises one circular chromosome of 3.5 Mb and contains no toxigenic and antibiotic resistance genes, providing molecular information to support the strain's safety and usage as a probiotic.

New Medicare Technology Add-On Payment Could Be Used As A Market Support Mechanism To Accelerate Antibiotic Innovation.

Despite growing antibiotic resistance, the clinical drug development pipeline for antibiotics has been sparse largely because of an unsustainable business model. We illustrate three models to accelerate antibiotic development, using Medicare new technology add-on payments as a market support mechanism. The first two models subsidize drug development for Medicare beneficiaries, and the third model applies a payment for every patient with a resistant infection to essentially create a funding pool. We found that the reimbursement required to sustain research and development would range from $637 to $121,365, depending on the payment model and the incidence of the resistant infection in question. With a $300 million public research subsidy, the payment for an antibiotic would drop to between $273 and $10,396 per course. Our market support model could increase the likelihood of attracting private investment for antibiotic development.

Activity data from wearables as an indicator of functional capacity in patients with cardiovascular disease.

BACKGROUND: Smartphone and wearable-based activity data provide an opportunity to remotely monitor functional capacity in patients. In this study, we assessed the ability of a home-based 6-minute walk test (6MWT) as well as passively collected activity data to supplement or even replace the in-clinic 6MWTs in patients with cardiovascular disease. METHODS: We enrolled 110 participants who were scheduled for vascular or cardiac procedures. Each participant was supplied with an iPhone and an Apple Watch running the VascTrac research app and was followed for 6 months. Supervised 6MWTs were performed during clinic visits at scheduled intervals. Weekly at-home 6MWTs were performed via the VascTrac app. The app passively collected activity data such as daily step counts. Logistic regression with forward feature selection was used to assess at-home 6MWT and passive data as predictors for "frailty" as measured by the gold-standard supervised 6MWT. Frailty was defined as walking <300m on an in-clinic 6MWT. RESULTS: Under a supervised in-clinic setting, the smartphone and Apple Watch with the VascTrac app were able to accurately assess 'frailty' with sensitivity of 90% and specificity of 85%. Outside the clinic in an unsupervised setting, the home-based 6MWT is 83% sensitive and 60% specific in assessing "frailty." Passive data collected at home were nearly as accurate at predicting frailty on a clinic-based 6MWT as was a home-based 6MWT, with area under curve (AUC) of 0.643 and 0.704, respectively. CONCLUSIONS: In this longitudinal observational study, passive activity data acquired by an iPhone and Apple Watch were an accurate predictor of in-clinic 6MWT performance. This finding suggests that frailty and functional capacity could be monitored and evaluated remotely in patients with cardiovascular disease, enabling safer and higher resolution monitoring of patients.

Reliability and repeatability of a smartphone-based 6-min walk test as a patient-centred outcome measure.

Aims: The 6-min-walk test (6MWT) is a validated proxy for frailty and a predictor of clinical outcomes, yet is not widely used due to implementation challenges. This comparative effectiveness study assesses the reliability and repeatability of a home-based 6MWT compared to in-clinic 6MWTs in patients with cardiovascular disease. Methods and results: One hundred and ten (110) patients scheduled for cardiac or vascular surgery were enrolled during a study period from June 2018 to December 2019 at the Palo Alto VA Hospital. Subjects were provided with an Apple iPhone 7 and Apple Watch Series 3 loaded with the VascTrac research study application and performed a supervised in-clinic 6MWT during enrolment, at 2 weeks, 1, 3, and 6 months post-operatively. Subjects also received notifications to perform at-home smartphone-based 6MWTs once a week for a duration of 6 months. Test-retest reliability of in-clinic measurements and at-home measurements was assessed with an industry standard Cronbach's alpha reliability test. Test-retest reliability for in-clinic ground truth 6MWT steps vs. in-clinic iPhone 6MWT steps was 0·99, showing high reliability between the two tested measurements. When comparing for in-clinic ground truth 6MWT steps vs. neighbouring at-home iPhone 6MWT steps, reliability was 0·74. Conclusion: Running the test-reliability test on both measurements shows that an iPhone 6MWT test is reliable compared to an in-clinic ground truth measurement in patients with cardiovascular disease.

Erratum: Author Correction: Clinical validation of smartphone-based activity tracking in peripheral artery disease patients.

[This corrects the article DOI: 10.1038/s41746-018-0073-x.].

National assessment of availability, awareness, and utilization of supervised exercise therapy for peripheral artery disease patients with intermittent claudication.

BACKGROUND: Supervised exercise therapy (SET) is an inexpensive, low-risk, and effective option when compared with invasive therapies for the treatment of patients with peripheral artery disease (PAD) and intermittent claudication. Randomized, controlled trials have demonstrated the benefits of SET in improving maximum walking distance in intermittent claudication patients, and society guidelines recommend SET as first-line therapy. In 2017, the Centers for Medicare & Medicaid Services (CMS) added coverage of SET. We aimed to evaluate the availability and use of SET programs, determine the awareness of SET CMS coverage in the United States, and gauge the academic interest in SET in the vascular community. METHODS: An eight-question online survey regarding SET coverage, reimbursement, barriers to prescription, and SET use was sent to 900 vascular surgeons, cardiologists, and vascular medicine physicians across the United States. The most recent 2-year programs for the Vascular Annual Meeting, Midwestern Vascular Society, Eastern Vascular Society, and Western Vascular Society were reviewed to identify SET-related abstracts and gauge academic interest and awareness for SET within the vascular surgery community. RESULTS: We received 135 physician responses (15%) to the survey. All 50 states were represented. The majority of responders (54%) stated that there was no SET program at their facility, and 5% did not know if there was a SET program available. Of those who did have a SET program available, 81% were associated with cardiac rehabilitation and 19% had a PAD-specific program. A significant number of physicians (49%) had never referred a patient for SET. Twenty-six percent were not aware that CMS covered SET sessions. Of the physicians who were aware of CMS reimbursement, 36% had never referred a patient to a SET program. Of all surveyed, 98% indicated they would refer patients to a SET program if one was available. Top barriers to use of a SET program included (1) no SET center availability and (2) significant cost or travel expense to the patient. A review of major vascular surgery meeting programs for the last 2 years yielded no identification of a SET-related abstract. CONCLUSIONS: There is a lack of both availability and use of SET for patients with PAD with claudication, despite guideline recommendations and CMS reimbursement for SET sessions in the United States. When SET is offered, it is typically through cardiac rehabilitation programs which is not focused on PAD. Travel distance, lack of SET program availability, and low reimbursement rates are primary areas that could be addressed to improve use.

Clinical validation of smartphone-based activity tracking in peripheral artery disease patients.

Peripheral artery disease (PAD) is a vascular disease that leads to reduced blood flow to the limbs, often causing claudication symptoms that impair patients' ability to walk. The distance walked during a 6-min walk test (6MWT) correlates well with patient claudication symptoms, so we developed the VascTrac iPhone app as a platform for monitoring PAD using a digital 6MWT. In this study, we evaluate the accuracy of the built-in iPhone distance and step-counting algorithms during 6MWTs. One hundred and fourteen (114) participants with PAD performed a supervised 6MWT using the VascTrac app while simultaneously wearing an ActiGraph GT9X Activity Monitor. Steps and distance-walked during the 6MWT were manually measured and used to assess the bias in the iPhone CMPedometer algorithms. The iPhone CMPedometer step algorithm underestimated steps with a bias of -7.2% ± 13.8% (mean ± SD) and had a mean percent difference with the Actigraph (Actigraph-iPhone) of 5.7% ± 20.5%. The iPhone CMPedometer distance algorithm overestimated distance with a bias of 43% ± 42% due to overestimation in stride length. Our correction factor improved distance estimation to 8% ± 32%. The Ankle-Brachial Index (ABI) correlated poorly with steps (R = 0.365) and distance (R = 0.413). Thus, in PAD patients, the iPhone's built-in distance algorithm is unable to accurately measure distance, suggesting that custom algorithms are necessary for using iPhones as a platform for monitoring distance walked in PAD patients. Although the iPhone accurately measured steps, more research is necessary to establish step counting as a clinically meaningful metric for PAD.

Nontherapeutic neonatal hypothermia.

The case presented advocates for prolonged resuscitation, and aggressive rewarming in neonates with severe hypothermia (core temperature <32.0°C). The importance of rewarming has not been extensively studied in current guidelines, whereas the importance of cardiopulmonary resuscitation is well established. This abandoned, severely hypothermic (found with temperature of 27.9°C) newborn had an excellent neurological outcome at two years of age with aggressive resuscitation and rewarming techniques initiated at the time of presentation. Active core rewarming with warm saline lavages, intravenous fluids and warm air may be used at a rate of 1.8°C/h to 5.3°C/h according to most guidelines. Rewarming guidelines for asphyxiated infants undergoing therapeutic hypothermic may not be applicable to infants with accidental exposure, as in the present case. The present case of a near-term severely hypothermic infant reinforces the current recommendation of continuing resuscitative measures, irrespective of response to resuscitation, until the infant has been rewarmed.

Le cas présenté plaide en faveur d'une réanimation prolongée et d'un réchauffement agressif chez les nouveau-nés présentant une grave hypothermie (température centrale de moins de 32,0 °C). Les directives à jour ne contiennent pas d'étude approfondie sur l'importance du réchauffement, mais celle de la réanimation cardiorespiratoire est bien établie. Ce nouveau-né abandonné en hypothermie grave (température de 27,9 °C lorsqu'il a été trouvé) présentait d'excellents résultats neurologiques à l'âge de deux ans, alors que des techniques de réanimation et de réchauffement agressives avaient été adoptées au moment de la présentation. On peut procéder au réchauffement actif de la température centrale à l'aide de lavages de sérum physiologique tiède, de liquides intraveineux et d'air tiède, à un rythme de 1,8 °C/h à 5,3 °C/h selon la plupart des directives. Les directives sur le réchauffement des nourrissons asphyxiés qui subissent une hypothermie thérapeutique ne s'appliquent peut-être pas aux nourrissons exposés accidentellement aux éléments, comme dans le cas présent. Ce cas d'un nourrisson presque à terme en grave hypothermie renforce la recommandation actuelle de poursuivre les mesures de réanimation, quelle que soit la réponse, jusqu'à ce que le nourrisson soit réchauffé.