Oxygen uptake plateau occurrence depends on oxygen kinetics and oxygen deficit accumulation

We tested the hypothesis that participants with an oxygen uptake () plateau during incremental exercise exhibit a lower VO₂‐deficit (VO_2DEF)‐accumulation in the submaximal intensity domain due to faster ramp and square wave O₂‐kinetics. Twenty‐six male participants performed a standard ramp test (increment: 30 W·min^?1), a ramp test with an individualized ramp slope and a two‐step (moderate and severe) square wave exercise followed by a ‐verification bout. VO_2DEF was calculated by the difference between individualized ramp test O₂ and O₂‐demand estimated from steady‐state O₂‐kinetics. Twenty‐four participants verified their O_2max in the verification test. Ten of them showed a plateau in the individualized ramp test. VO_2DEF at the end of this ramp test (4.34 ± 0.60 vs 4.54 ± 0.43 L) was not different between the plateau and the non‐plateau group (P > 0.05). The plateau group had a significantly (P < 0.05) lower VO_2DEF 2 minutes before termination of the individualized ramp test (2.24 ± 0.40 vs 2.78 ± 0.33 L). This coincided with a shorter mean response time (43 ± 9 vs 53 ± 7 seconds), a higher increase in O₂ per W (10.1 ± 0.2 vs 9.2 ± 0.5 mL·min^?1·W^?1) at the individualized ramp test as well as shorter time constants of moderate (36 ± 6 vs 48 ± 7 seconds) and severe (62 ± 9 vs 86 ± 10 seconds) square wave kinetics (all P < 0.05). We conclude that the O₂‐plateau occurrence requires a fast O₂‐kinetics and a low VO_2DEF‐accumulation at intensities below O_2max.     

Humans and machines: Moving towards a more symbiotic approach to learning clinical reasoning

Abstract

Artificial intelligence is a growing phenomenon that is driving major changes to how we deliver healthcare. One of its most significant and challenging contributions is likely to be in diagnosis. Artificial intelligence is challenging the physician’s exclusive role in diagnosis and in some areas, its diagnostic accuracy exceeds that of humans. We argue that we urgently need to consider how we will incorporate AI into our teaching of clinical reasoning in the undergraduate curriculum; students need to successfully navigate the benefits and potential issues of new and developing approaches to AI in clinical diagnosis. We offer a pedagogical framework for this challenging change to our curriculum.     

Uveitis in Patients Treated with CTLA-4 and PD-1 Checkpoint Blockade Inhibition

ABSTRACT

Purpose: To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis.

Methods: A survey was distributed to uveitis specialists to identify patients who developed uveitis while receiving either PD-1 inhibitors pembrolizumab and nivolumab; PD-L1 inhibitors atezolizumab, avelumab, and durvalumab; or the CTLA-4 inhibitor ipilimumab.

Results: Fifteen patients from seven institutions were identified. The most common cancer diagnosis (13/15) was malignant melanoma. Fourteen patients had a new uveitis diagnosis following checkpoint blockade administration (six anterior uveitis, six panuveitis, one posterior uveitis, one anterior/intermediate combined); one patient developed optic neuritis. Uveitis was diagnosed within 6 months after drug initiation for 11/12 patients (median 63 days). Corticosteroid treatment was effective for most patients, although two patients had permanent loss of vision.

Conclusions: Patients on checkpoint inhibitor therapy should be educated to seek care if they develop ocular symptoms, and prompt referral to specialists should be incorporated into oncology protocols.     

A Canadian Prospective Study of Linkage of Randomized Clinical Trial to Cancer and Mortality Registry Data

In a prospective study, we sought to determine acceptability of linkage of administrative and clinical trial data among Canadian patients and Research Ethics Boards (REBs). The goal is to develop a more harmonized approach to data, with potential to improve clinical trial conduct through enhanced data quality collected at reduced cost and inconvenience for patients. On completion of the original LY.12 randomized clinical trial in lymphoma ({"type":"clinical-trial","attrs":{"text":"NCT00078949","term_id":"NCT00078949"}}NCT00078949), participants were invited to enrol in the Long-term Innovative Follow-up Extension (LIFE) component. Those consenting to do so provided comprehensive identifying information to facilitate linkage with their administrative data. We prospectively designed a global assessment of this innovative approach to clinical trial follow-up including rates of REB approval and patient consent. The pre-specified benchmark for patient acceptability was 80%. Of 16 REBs who reviewed the research protocol, 14 (89%) provided approval; two in Quebec declined due to small patient numbers. Of 140 patients invited to participate, 115 (82%, 95% CI 76 to 88%) from across 9 Canadian provinces provided consent and their full name, date of birth, health insurance number and postal code to facilitate linkage with their administrative data for long-term follow-up. Linkage of clinical trial and administrative data is feasible and acceptable. Further collaborative work including many stakeholders is required to develop an optimized secure approach to research. A more coordinated national approach to health data could facilitate more rapid testing and identification of new effective treatments across multiple jurisdictions and diseases from diabetes to COVID-19.     

Der lange Weg von der Idee bis zur Erstattung – ein Reisebericht

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Digitale Gesundheitsprodukte und -dienstleistungen beginnen sowohl die Versorgung von Kranken als auch die Prävention...     

Canalicular adenoma of the palate: case report and literature review

Canalicular adenoma is a rare benign salivary gland tumor of the oral cavity, typically located in the upper lip and buccal mucosa and infrequently found on the palate. The tumor is usually confined to soft tissue and rarely presents with bone erosion. A case of a large and locally-aggressive palatal canalicular adenoma is presented. The lesion presented herein was an asymptomatic ulcerated mass with significant bone erosion. The tumor was managed surgically with excision and reconstruction of the resulting palatal defect with a full temporalis muscle flap.     

Using extracted teeth for research: the effect of storage medium and sterilization on dentin bond strengths

BACKGROUND: The Centers for Disease Control and Prevention has adopted guidelines for infection control of extracted teeth used for research and teaching, requiring that teeth be sterilized before use. The authors conducted a study to test the null hypothesis that the storage medium and sterilization method have no effect on composite-to-dentin bond strengths. MATERIALS AND METHODS: The authors collected 170 bovine incisors, cleaned them and placed them randomly into one of six storage media at 37 degrees C for 60 days: distilled water (dH(2)O), 0.9 percent sodium chloride, 0.5 percent chloramine-T, 5.25 percent sodium hypochlorite (NaClO), 2 percent glutaraldehyde and 10 percent formalin. For sterilization, they autoclaved a subset of 10 specimens from every sample, while they stored another subset of 10 specimens from every sample (except for the 10 percent formalin sample) in 10 percent formalin for 14 days. The authors then embedded the specimens in epoxy and ground flat the facial surface to expose middle-depth dentin, which they polished to 600 grit. They used a dental adhesive to apply composite to the exposed dentin. The authors tested the composite-to-dentin shear bond strength 24 hours after bonding. They analyzed the data using global analysis of variance and, when appropriate, multiple post hoc tests (P = .05). RESULTS: Storage in NaClO resulted in significantly lower bond strength than that of the other treatment specimens. Sterilization with the autoclave negatively affected the bond strength of specimens stored initially in dH(2)O or 10 percent formalin, while sterilization with formalin alone had no significant effect on bond strengths. CONCLUSIONS: Storing bovine teeth in 5.25 percent NaClO may negatively affect composite-to-dentin bond strengths. Immersion in 10 percent formalin might be the best option for storage and sterilization of bovine teeth that are to be used in dental bonding studies in vitro.