A systematic scoping review and content analysis of organizational health literacy responsiveness assessment tools.

The characteristics of health literate organizations have been variously described in recognition that it is important for organizations to respond to the diversity of people's health literacy strengths and challenges. A systematic scoping review was conducted to identify, assess and classify international self-assessment tools aimed at measuring the capability of organizations to embody health literate characteristics. Following the JBI Scoping Manual, a search was conducted in six databases and identified 2693 articles. After screening, 16 studies published between 2007 and 2023 across eight countries were eligible for inclusion. Results were summarized and a finite list of items from existing tools was generated. Content analysis was performed to classify these items. Whilst most assessment tools in the included studies were healthcare-focused, other settings included schools and government departments. The 16 assessment tools included a total of 661 items, and 647 items were retained that met the definition of health literacy responsiveness. Items were classified into six domains (communication; navigation of resources; culture; policies and practice; involvement or engagement and workforce development), with high agreement between two researchers (91.5%). The 647 items were reviewed to exclude items that were too contextually specific, focused solely on service users, were too broad or had suitable alternatives; 210 items were finally retained. This research is two-fold: provides a synthesis of existing organizational health literacy responsiveness assessment tools across settings; and provides a list of items, which will be essential to developing context specific assessment tools through Delphi methods in the future.

CDK4/6 inhibitors in metastatic breast cancer, a comparison of toxicity and efficacy across agents in a real-world dataset.

INTRODUCTION: CDK4/6 inhibitors (ribociclib, palbociclib and abemaciclib) are 1st line therapy in metastatic breast cancer (MBC). No comparative data exists between agents regarding toxicity or efficacy. METHODS: A retrospective study was performed at our tertiary referral centre evaluating patients on a CDK4/6 inhibitor for MBC between July 2017 and December 2021. Toxicity was evaluated along with variability in full blood counts and liver function over the first 12 weeks of therapy. RESULTS: Two hundred and seventeen patients were treated (palbociclib 59%, abemaciclib 25% and ribociclib 16%). 86% received the agent as 1st line therapy. Most patients were white women with a median age of 61 years (32-95) and ECOG 0/1. Twelve patients were switched to an alternative CDK4/6 inhibitor due to toxicity and two did not tolerate this. Toxicity profiles of agents were consistent with published trials. However, there was greater overlap in hepatitis, diarrhoea and bone marrow suppression. Blood results indicated a minimum of four weeks treatment before development of neutropenia. Forty percent of patients went onto have subsequent lines of therapy. The progression-free survival per agent was palbociclib 27.9 months (95% CI 23-32.5), ribociclib 29 months (95% CI 21.5-37.0) and abemaciclib 20.6 months (95% CI 15.0-26.0). The overall survival was palbociclib 38.0 months (95% CI 33.5-42.5), ribociclib 33.9 months (95% CI 26.7-41.1) and abemaciclib 27.3 months (95% CI 22.5-32.1). CONCLUSIONS: Toxicity across CDK4/6 inhibitors overlaps. The optimal sequence of therapies post CDK4/6 inhibitors remains unknown but rechallenge with an alternative agent is possible.

An investigation of the use of app technology to support clinical management of patients with chronic myeloid leukaemia (CML).

INTRODUCTION: The availability of healthcare apps to support patient self-management of various medical conditions, including cancer, has increased considerably in the past decade. However, there are limited published data on the role of apps in the management of chronic myeloid leukaemia (CML). The primary aim of this study was to investigate the current and future role of apps as a means of supporting patients with CML. METHODS: A 31-item questionnaire was developed and distributed to patients via three on-line CML support groups. RESULTS: Responses were received from 286 patients. There was an approximate 2:1 female: male split and the majority (54%, n = 155) resided in the United Kingdom. 91% (n = 260) of respondents were currently receiving drug treatment for their CML. 23.4% (n = 67) of respondents were aware that apps were available to support their CML management and 11.5% (n = 33) had experience of using such an app. 94.1% (n = 238) of those who had not used a patient support app in the past stated that they would consider using an app in the future to help manage their disease. App awareness was significantly higher amongst male patients (30.3% vs. 19.9%). Likelihood of being a current or previous app user was higher amongst younger patients (16.3% for <55 years old vs. 5.6% for ≥55 years old) whilst younger patients and those with a more recent diagnosis of CML were both more likely to be interested in using an app in the future. When asked about potential app functionality, a drug interaction checker was the feature of greatest interest to respondents. CONCLUSIONS: We have identified both a lack of awareness of and a low uptake of patient support apps amongst CML patients. Importantly, we have demonstrated a clear interest in CML-specific apps amongst this population. Based on the functionality that study participants were most interested in, we will work with health care professionals, app developers and patients to develop a new app to deliver holistic support to CML patients.

Tracking adiponectin biodistribution via fluorescence molecular tomography indicates increased vascular permeability after streptozotocin-induced diabetes.

Adiponectin, a highly abundant polypeptide hormone in plasma, plays an important role in the regulation of energy metabolism in a wide variety of tissues, as well as providing important beneficial effects in diabetes, inflammation, and cardiovascular disease. To act on target tissues, adiponectin must move from the circulation to the interstitial space, suggesting that vascular permeability plays an important role in regulating adiponectin action. To test this hypothesis, fluorescently labeled adiponectin was used to monitor its biodistribution in mice with streptozotocin-induced diabetes (STZD). Adiponectin was, indeed, found to have increased sequestration in the highly fenestrated liver and other tissues within 90 min in STZD mice. In addition, increased myocardial adiponectin was detected and confirmed using computed tomography (CT) coregistration. This provided support of adiponectin delivery to affected cardiac tissue as a cardioprotective mechanism. Higher adiponectin content in the STZD heart tissues was further examined by ex vivo fluorescence molecular tomography (FMT) imaging, immunohistochemistry, and Western blot analysis. In vitro mechanistic studies using an endothelial monolayer on inserts and three-dimensional microvascular networks on microfluidic chips further confirmed that adiponectin flux was increased by high glucose. However, in the in vitro model and mouse heart tissue, high glucose levels did not change adiponectin receptor levels. An examination of the tight junction (TJ) complex revealed a decrease in the TJ protein claudin (CLDN)-7 in high glucose-treated endothelial cells, and the functional significance of this change was underscored by increased endothelium permeability upon siRNA-mediated knockdown of CLDN-7. Our data support the idea that glucose-induced effects on permeability of the vascular endothelium contribute to the actions of adiponectin by regulating its transendothelial movement from blood to the interstitial space. These observations are physiologically significant and critical when considering ways to harness the therapeutic potential of adiponectin for diabetes.

Intracellular Abeta is increased by okadaic acid exposure in transfected neuronal and non-neuronal cell lines.

Intracellular Abeta was examined in both a neuronal cell line (B103) expressing human APP with Swedish mutation and a non-neuronal cell line (Chinese hamster ovary, CHO) expressing wild human APP. Exposure of the APP695sw-transfected B103 cells to okadaic acid for 3 h, Abeta immunostaining was enhanced, as demonstrated by two independent anti-Abeta antibodies. The confocal microscopic study revealed that the immunoreactivity of Abeta was mainly colocalized with a Golgi marker and partially with an ER marker. Quantitative analyses, using Abeta sandwich ELISA, showed significantly increased intracellular Abeta. False positive detection of Abeta by antibody cross-reaction with APP was ruled out by extracting the fraction with formic acid and making it alkaline before subjecting it to ELISA. This procedure resulted in a fraction that contained little APP. Using CHO cells, OA treatment was also shown to be effective in increasing Abeta, as demonstrated by Western blot. The increased full-length APP and decreased APPC99 were also observed. This is the first study to demonstrate that OA treatment significantly increases intracellular Abeta.

Comparative analyses of a small molecule/enzyme interaction by multiple users of Biacore technology.

To gauge the experimental variability associated with Biacore analysis, 36 different investigators analyzed a small molecule/enzyme interaction under similar conditions. Acetazolamide (222 g/mol) binding to carbonic anhydrase II (CAII; 30000 Da) was chosen as a model system. Both reagents were stable and their interaction posed a challenge to measure because of the low molecular weight of the analyte and the fast association rate constant. Each investigator created three different density surfaces of CAII and analyzed an identical dilution series of acetazolamide (ranging from 4.1 to 1000 nM). The greatest variability in the results was observed during the enzyme immobilization step since each investigator provided their own surface activating reagents. Variability in the quality of the acetazolamide binding responses was likely a product of how well the investigators' instruments had been maintained. To determine the reaction kinetics, the responses from the different density surfaces were fit globally to a 1:1 interaction model that included a term for mass transport. The averaged association and dissociation rate constants were 3.1+/-1.6 x 10(6)M(-1)s(-1) and 6.7+/-2.5 x 10(-2)s(-1), respectively, which corresponded to an average equilibrium dissociation constant (K(D) of 2.6+/-1.4 x 10(-8)M. The results provide a benchmark of variability in interpreting binding constants from the biosensor and highlight keys areas that should be considered when analyzing small molecule interactions.