Experimental group B streptococcal endocarditis treated with penicillin G versus ceftizoxime. In vitro-in vivo disparity

Aortic valve endocarditis due to a penicillin G (PNC) and ceftizoxime (CZ)-sensitive group B streptococcus (GBS) was induced in 72 rabbits. Animals received either procaine PNC (300 mg/kg per day) or CZ (150 mg/kg/day) for 3, 6, or 9 days. PNC rapidly sterilized blood cultures (less than or equal to 3 days) and significantly reduced vegetation GBS titers versus controls at all three sacrifice times (p less than 0.0005). In contrast, CZ exerted a slow in vivo bactericidal effect with vegetation titers not significantly different from controls until day 9 of therapy. By day 9 of therapy, 65/89 (73%) of vegetations were sterilized by PNC versus only 24/94 (26%) sterilized by CZ (p less than 0.0005). This marked in vitro-in vivo disparity in CZ-treated animals occurred despite 100% of individual serum bactericidal titers greater than or equal to 1:32 and 100% of individual CZ serum levels greater than or equal to 100 times the GBS MBC. The suboptimal CZ in vivo effect was not related to: (1) development of CZ resistance on therapy; (2) CZ inactivation, or (3) inoculum-growth phase effect.     

Monovalent cation transport in irreversibly sickled cells.

Using discontinuous density gradients of Stractan II, we have separated sickle cell blood into discrete subpopulations of reticulocytes, mature discoid cells, and irreversibly sickled cells (ISCs). We have measured active and passive fluxes of monovalent cations in mature discoid cells, ISCs, and normal control cells, also separated upon density gradients. These measurements revealed a decreased active cation transport in ISC-rich populations. However, parallel measurements of Na, K-ATPase activity showed normal ouabain-sensitive ATPase activity in ISCs. Passive permeability to external Rb was also normal in ISCs. The observation of depressed pump activity in intact ISCs, contrasted with normal ATPase activity in ISC membranes, suggests the presence of factors in the intact cell which inhibit the active transport of Na and K in ISCs.     

Feasibility Study and Clinical Impact of Incorporating Breast Tissue Density in High-Risk Breast Cancer Screening Assessment

Breast tissue density (BTD) is known to increase the risk of breast cancer but is not routinely used in the risk assessment of the population-based High-Risk Ontario Breast Screening Program (HROBSP). This prospective, IRB-approved study assessed the feasibility and impact of incorporating breast tissue density (BTD) into the risk assessment of women referred to HROBSP who were not genetic mutation carriers. All consecutive women aged 40–69 years who met criteria for HROBSP assessment and referred to Genetics from 1 December 2020 to 31 July 2021 had their lifetime risk calculated with and without BTD using Tyrer-Cuzick model version 8 (IBISv8) to gauge overall impact. McNemar’s test was performed to compare eligibility with and without density. 140 women were referred, and 1 was excluded (BRCA gene mutation carrier and automatically eligible). Eight of 139 (5.8%) never had a mammogram, while 17/131 (13%) did not have BTD reported on their mammogram and required radiologist review. Of 131 patients, 22 (16.8%) were clinically impacted by incorporation of BTD: 9/131 (6.9%) became eligible for HROBSP, while 13/131 (9.9%) became ineligible (p = 0.394). It was feasible for the Genetics clinic to incorporate BTD for better risk stratification of eligible women. This did not significantly impact the number of eligible women while optimizing the use of high-risk supplemental MRI screening.     

Design details for overdose education and take‐home naloxone kits: Codesign with family medicine,emergency department,addictions medicine and community

IntroductionOverdose education and naloxone distribution (OEND) programmes equip and train people who are likely to witness an opioid overdose to respond with effective first aid interventions. Despite OEND expansion across North America, overdose rates are increasing, raising questions about how to improve OEND programmes. We conducted an iterative series of codesign stakeholder workshops to develop a prototype for take‐home naloxone (THN)‐kit (i.e., two doses of intranasal naloxone and training on how to administer it).MethodsWe recruited people who use opioids, frontline healthcare providers and public health representatives to participate in codesign workshops covering questions related to THN‐kit prototypes, training on how to use it, and implementation, including refinement of design artefacts using personas and journey maps. Completed over 9 months, the workshops were audio‐recorded and transcribed with visible results of the workshops (i.e., sticky notes, sketches) archived. We used thematic analyses of these materials to identify design requirements for THN‐kits and training.ResultsWe facilitated 13 codesign workshops to identify and address gaps in existing opioid overdose education training and THN‐kits and emphasize timely response and stigma in future THN‐kit design. Using an iterative process, we created 15 prototypes, 3 candidate prototypes and a final prototype THN‐kit from the synthesis of the codesign workshops.ConclusionThe final prototype is available for a variety of implementation and evaluation processes. The THN‐kit offers an integrated solution combining ultra‐brief training animation and physical packaging of nasal naloxone to be distributed in family practice clinics, emergency departments, addiction medicine clinics and community settings.Patient or Public ContributionThe codesign process was deliberately structured to involve community members (the public), with multiple opportunities for public contribution. In addition, patient/public participation was a principle for the management and structuring of the research team.     

Processed Food as a Risk Factor for the Development and Perpetuation of Crohn’s Disease—The ENIGMA Study

(1) Background: Developing countries have experienced a rapid recent rise in Inflammatory Bowel Disease (IBD) incidence and emerging evidence suggests processed foods and food additives may predispose one to the development and perpetuation of Crohn’s disease (CD). The aim of this study was to evaluate processed food and food additive intake in CD patients and controls, in Australia (high CD incidence), Hong Kong (intermediate incidence) and mainland China (emerging incidence). (2) Methods: In 274 CD patients (CD), 82 first-degree relatives (FDR), 83 household members (HM) and 92 healthy unrelated controls (HC) from Australia (n = 180), Hong Kong (HK) (n = 160) and mainland China (n = 191) we estimated early life (0–18 years), recent (12 months), and current processed and food additive intake, using validated questionnaires and a 3-day-food diary. (3) Results: Early life processed food intake: Combining all regions, CD were more likely to have consumed soft drinks and fast foods than HM, more likely to have consumed processed fruit and snacks than their FDR, and more likely to have consumed a range of processed foods than HC. HK and China CD patients were more likely to have consumed a range of processed foods than HC. Recent food-additive intake (12-months): Combining all regions, CD patients had significantly higher intakes of aspartame and sucralose, and polysorbate-80, than HC, and more total emulsifiers, artificial sweeteners, and titanium dioxide than FDR and HC. HK and China CD patients had a higher intake of almost all food additives than all controls. Current additive intake (3-days): Australian and HK CD patients had higher total food-additive intake than FDR, and HK CD patients had a higher intake of total food-additives and emulsifiers than HM. (4) Conclusions: CD patients have been exposed to more processed food and food additives than control groups, which may predispose them to CD development and ongoing inflammation.