Xanthomonas Phage PBR31: Classifying the Unclassifiable.

The ability of bacteriophages to destroy bacteria has made them the subject of extensive research. Interest in bacteriophages has recently increased due to the spread of drug-resistant bacteria, although genomic research has not kept pace with the growth of genomic data. Genomic analysis and, especially, the taxonomic description of bacteriophages are often difficult due to the peculiarities of the evolution of bacteriophages, which often includes the horizontal transfer of genes and genomic modules. The latter is particularly pronounced for temperate bacteriophages, which are capable of integration into the bacterial chromosome. Xanthomonas phage PBR31 is a temperate bacteriophage, which has been neither described nor classified previously, that infects the plant pathogen Xanthomonas campestris pv. campestris. Genomic analysis, including phylogenetic studies, indicated the separation of phage PBR31 from known classified bacteriophages, as well as its distant relationship with other temperate bacteriophages, including the Lederbervirus group. Bioinformatic analysis of proteins revealed distinctive features of PBR31, including the presence of a protein similar to the small subunit of D-family DNA polymerase and advanced lysis machinery. Taxonomic analysis showed the possibility of assigning phage PBR31 to a new taxon, although the complete taxonomic description of Xanthomonas phage PBR31 and other related bacteriophages is complicated by the complex evolutionary history of the formation of its genome. The general biological features of the PBR31 phage were analysed for the first time. Due to its presumably temperate lifestyle, there is doubt as to whether the PBR31 phage is appropriate for phage control purposes. Bioinformatics analysis, however, revealed the presence of cell wall-degrading enzymes that can be utilised for the treatment of bacterial infections.

Characterisation of New Foxunavirus Phage Murka with the Potential of Xanthomonas campestris pv. campestris Control.

Phages of phytopathogenic bacteria are considered to be promising agents for the biological control of bacterial diseases in plants. This paper reports on the isolation and characterisation of a new Xanthomonas campestris pv. campestris phage, Murka. Phage morphology and basic kinetic characteristics of the infection were determined, and a phylogenomic analysis was performed. The phage was able to lyse a reasonably broad range (64%, 9 of the 14 of the Xanthomonas campestris pv. campestris strains used in the study) of circulating strains of the cabbage black rot pathogen. This lytic myovirus has a DNA genome of 44,044 bp and contains 83 predicted genes. Taxonomically, it belongs to the genus Foxunavirus. This bacteriophage is promising for use as a possible means of biological control of cabbage black rot.

Measure of Caregiver Attention-Deficit/Hyperactivity Disorder Knowledge Is Responsive to Decision Aid on Treatment for Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Adapt and test a measure of knowledge for caregivers of children with attention-deficit/hyperactivity disorder (ADHD) and evaluate the impact of the information component of a decision aid (DA) on participant knowledge. METHODS: A set of seven knowledge items were created based on prior knowledge measures and clinical guidelines. As part of a larger cross-sectional survey study of caregivers of children diagnosed with ADHD, caregivers were randomized to one of two arms: 1) a DA arm, where participants reviewed the information component of the Cincinnati Children's Hospital's DA, and 2) a control arm, where participants were not shown a DA. All participants completed the seven knowledge items. Knowledge items were assessed for difficulty, quality of distractors, acceptability, and redundancy. Total knowledge scores (0-100) for the DA and control arm were compared. RESULTS: Caregivers were assigned to the DA arm (n = 243) or the control arm (n = 260). All 7 knowledge items were retained as no items were too difficult or too easy, all response options were used, there were little missing data, and no items were redundant. The overall knowledge score was normally distributed, and almost covered the full range of scores (5-100). Those who received the DA component had higher knowledge scores (M=68, SD=23) than those who did not receive the DA component (M=60, SD=19, P < .01, d=0.4). CONCLUSIONS: The Caregiver ADHD Knowledge (CAKe) measure was acceptable and demonstrated construct validity as those who were assigned to review the DA component demonstrated greater knowledge than those who were not assigned to review the DA component.

Vitamin A, D, E, and K as Matrix Metalloproteinase-2/9 Regulators That Affect Expression and Enzymatic Activity.

Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these vitamins is imperative to the upkeep of various physiological processes including vision, bone health, immunity, and protection against oxidative stress. Current research highlights fat-soluble vitamins as potential therapeutics for human diseases, especially cancer. Fat-soluble vitamins exert their therapeutic effects through multiple pathways, including regulation of matrix metalloproteinases' (MMPs) expression and enzymatic activity. As MMPs have been reported to be involved in the pathology of various diseases, such as cancers, cardiovascular diseases, and neurological disorders, regulating the expression and/or activity of MMPs could be considered as a potent therapeutic strategy. Here, we summarize the properties of fat-soluble vitamins and their potential as promising candidates capable of effectively modulating MMPs through multiple pathways to treat human diseases.

Drug-Related Problems and Pharmacists' Interventions in Hypertensive Outpatients: A Multicenter Prospective Study in 3 Vietnamese Hospitals.

Background: Clinical pharmacists' interventions (PIs) on drug-related problems (DRPs) in Vietnamese hypertensive outpatients are limited. Objectives: The objective was to investigate the prevalence and nature of DRPs, and factors which are likely to have DRPs, types of PIs, and their acceptance rate in 3 Vietnamese hospitals. Method: A prospective interventional study was conducted over a period of 3 months in 3 hospitals (from October 2021 to March 2022). Clinical pharmacists conducted medication reviews after collecting patient information from prescriptions and patient interviewing, and then identified the DRPs and suggested PIs according to the Vi-Med tool. These DRPs and PIs were reviewed by other superior clinical pharmacists and a consensus meeting with 3 cardiologists. Results: Of 381 patients included, 344 (90.23%) experienced 1 or more DRPs. A total of 820 DRPs were identified with an average of 2.15 DRPs per patient and 415 (50.61%) were hypertension-related issues. The most common DRPs identified were "administration mode" (46.34%), "missing indication" (18.05%), "non-conformity indication" (17.80%), and "dosage" (11.95%). Comorbidity (adjusted odds ratio [AOR] = 3.985, 95% CI: 1.597-9.942, P = 0.003) was the predictor of DRPs. Clinical pharmacists provided 739 PIs and 94.45% were accepted by physicians. Conclusion: The results of this study showed that DRPs were very common in hypertensive outpatients and highlighted the role of clinical pharmacists to identify and resolve DRPs through prompt interventions.

Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells.

High-grade serous ovarian cancer (HGSOC) is responsible for the majority of gynecology cancer-related deaths. Patients in remission often relapse with more aggressive forms of disease within 2 years post-treatment. Alternative immuno-oncology (IO) strategies, such as immune checkpoint blockade (ICB) targeting the PD-(L)1 signaling axis, have proven inefficient so far. Our aim is to utilize epigenetic modulators to maximize the benefit of personalized IO combinations in ex vivo 3D patient-derived platforms and in vivo syngeneic models. Using patient-derived tumor ascites, we optimized an ex vivo 3D screening platform (PDOTS), which employs autologous immune cells and circulating ascites-derived tumor cells, to rapidly test personalized IO combinations. Most importantly, patient responses to platinum chemotherapy and poly-ADP ribose polymerase inhibitors in 3D platforms recapitulate clinical responses. Furthermore, similar to clinical trial results, responses to ICB in PDOTS tend to be low and positively correlated with the frequency of CD3+ immune cells and EPCAM+/PD-L1+ tumor cells. Thus, the greatest response observed with anti-PD-1/anti-PD-L1 immunotherapy alone is seen in patient-derived HGSOC ascites, which present with high levels of systemic CD3+ and PD-L1+ expression in immune and tumor cells, respectively. In addition, priming with epigenetic adjuvants greatly potentiates ICB in ex vivo 3D testing platforms and in vivo tumor models. We further find that epigenetic priming induces increased tumor secretion of several key cytokines known to augment T and NK cell activation and cytotoxicity, including IL-6, IP-10 (CXCL10), KC (CXCL1), and RANTES (CCL5). Moreover, epigenetic priming alone and in combination with ICB immunotherapy in patient-derived PDOTS induces rapid upregulation of CD69, a reliable early activation of immune markers in both CD4+ and CD8+ T cells. Consequently, this functional precision medicine approach could rapidly identify personalized therapeutic combinations able to potentiate ICB, which is a great advantage, especially given the current clinical difficulty of testing a high number of potential combinations in patients.

Shared Decision Making for Elective Surgical Procedures in Older Adults with and without Cognitive Insufficiencies.

PURPOSE: Older adults are prone to cognitive impairment, which may affect their ability to engage in aspects of shared decision making (SDM) and their ability to complete surveys about the SDM process. This study examined the surgical decision-making processes of older adults with and without cognitive insufficiencies and evaluated the psychometric properties of the SDM Process scale. METHODS: Eligible patients were 65 y or older and scheduled for a preoperative appointment before elective surgery (e.g., arthroplasty). One week before the visit, staff contacted patients via phone to administer the baseline survey, including the SDM Process scale (range 0-4), SURE scale (top scored), and the Montreal Cognitive Assessment Test version 8.1 BLIND English (MoCA-blind; score range 0-22; scores < 19 indicate cognitive insufficiency). Patients completed a follow-up survey 3 mo after their visit to assess decision regret (top scored) and retest reliability for the SDM Process scale. RESULTS: Twenty-six percent (127/488) of eligible patients completed the survey; 121 were included in the analytic data set, and 85 provided sufficient follow-up data. Forty percent of patients (n = 49/121) had MoCA-blind scores indicating cognitive insufficiencies. Overall SDM Process scores did not differ by cognitive status (intact cognition x¯ = 2.5, s = 1.0 v. cognitive insufficiencies x¯ = 2.5, s = 1.0; P = 0.80). SURE top scores were similar across groups (83% intact cognition v. 90% cognitive insufficiencies; P = 0.43). While patients with intact cognition had less regret, the difference was not statistically significant (92% intact cognition v. 79% cognitive insufficiencies; P = 0.10). SDM Process scores had low missing data and good retest reliability (intraclass correlation coefficient = 0.7). CONCLUSIONS: Reported SDM, decisional conflict, and decision regret did not differ significantly for patients with and without cognitive insufficiencies. The SDM Process scale was an acceptable, reliable, and valid measure of SDM in patients with and without cognitive insufficiencies. HIGHLIGHTS: Forty percent of patients 65 y or older who were scheduled for elective surgery had scores indicative of cognitive insufficiencies.Patient-reported shared decision making, decisional conflict, and decision regret did not differ significantly for patients with and without cognitive insufficiencies.The Shared Decision Making Process scale was an acceptable, reliable, and valid measure of shared decision making in patients with and without cognitive insufficiencies.

Subclinical systolic dysfunction detected by 2D speckle tracking echocardiography in adults with diabetes mellitus: systematic review and meta-analysis of 6668 individuals with diabetes mellitus and 7218 controls.

PURPOSE: Speckle tracking echocardiography (STE) can help to identify subclinical features of diabetic cardiomyopathy (DCM). There is, however, significant heterogeneity in the reported strain values in literature. We performed a systematic review and meta-analysis to compare cardiac systolic strain values assessed by 2D-STE in asymptomatic adults with diabetes mellitus (DM) and healthy controls. METHODS: Five databases were searched, and a total of 41 valid studies (6668 individuals with DM and 7218 controls) were included for analysis. Pooled mean in each group and mean difference (MD) for left ventricular global longitudinal strain (LVGLS), LV global circumferential strain (LVGCS), LV global radial strain (LVGRS), LV longitudinal systolic strain rate (LVSR), left atrial reservoir strain (LARS) and right ventricular GLS (RVGLS) were assessed. RESULTS: Patients with DM had overall 2 units lower LVGLS than healthy subjects 17.5% [16.8, 18.3], vs 19.5 [18.7, 20.4], MD = - 1.96 [- 2.27, - 1.64]. Other strain values were also lower in patients with DM: LVGCS (MD = - 0.89 [- 1.26, - 0.51]); LVGRS (MD = - 5.03 [- 7.18, - 2.87]); LVSR (MD = - 0.06 [- 0.10, - 0.03]); LARS (MD = - 8.41 [- 11.5, - 5.33]); and RVGLS (MD = - 2.41 [- 3.60, - 1.22]). Meta-regression identified higher body mass index (BMI) as the single contributor to worse LVGLS, LVGCS and LVSR. Those with higher Hemoglobulin A1c had worse RVGLS. CONCLUSION: Myocardial strains were reduced in whole heart in patients with DM. The largest reduction was observed in LA reservoir strain, followed by RVGLS and LVGLS. Higher BMI in patients with DM is associated with worse LV strain values.

Evaluation of the shared decision-making process scale in cancer screening and medication decisions.

OBJECTIVES: Examine reliability and validity of the Shared Decision-Making (SDM) Process scale for cancer screening and medication decisions. METHODS: Secondary data analysis from 6174 participants who made decisions about cancer screening (breast, colon or prostate) or medication (menopause, depression, hypertension or high cholesterol). Key measures included the SDM Process scale, decisional conflict, decision regret, and decision quality. Construct validity was examined by testing whether higher SDM Process scores were associated with lower regret, lower decisional conflict and higher decision quality. Meta-analyses summarized data across studies. Some studies assessed the scale's reliability. RESULTS: Average SDM Process scores ranged from 1.2 to 2.5. There was a moderate-to-large, positive association between scores and lack of decisional conflict (cancer screening: d=0.61, CI(0.38, 0.84), p < .001; medications: d=0.36, CI(0.29, 0.44), p < .001). High scores were associated with lower decision regret (cancer screening: d=-0.24, CI(-0.37, -0.11), p < .001; medications: d=-0.30, CI(-0.40,-0.20), p < .001). There was no relationship with decision quality. Retest reliability was acceptable (ICC>0.7) for seven of eight clinical samples. CONCLUSIONS: The SDM Process scale demonstrated construct validity and retest reliability in cancer screening and medication decisions. PRACTICE IMPLICATIONS: The validated SDM Process scale is a short, patient reported metric to evaluate the current state of SDM.

Volatile organic compounds shape belowground plant-fungi interactions.

Volatile organic compounds (VOCs), a bouquet of chemical compounds released by all life forms, play essential roles in trophic interactions. VOCs can facilitate a large number of interactions with different organisms belowground. VOCs-regulated plant-plant or plant-insect interaction both below and aboveground has been reported extensively. Nevertheless, there is little information about the role of VOCs derived from soilborne pathogenic fungi and beneficial fungi, particularly mycorrhizae, in influencing plant performance. In this review, we show how plant VOCs regulate plant-soilborne pathogenic fungi and beneficial fungi (mycorrhizae) interactions. How fungal VOCs mediate plant-soilborne pathogenic and beneficial fungi interactions are presented and the most common methods to collect and analyze belowground volatiles are evaluated. Furthermore, we suggest a promising method for future research on belowground VOCs.

Pediatric Caregiver Version of the Shared Decision Making Process Scale: Validity and Reliability for ADHD Treatment Decisions.

OBJECTIVE: Shared decision making (SDM) is recommended for common pediatric conditions; however, there are limited data on measures of SDM in pediatrics. This study adapted the SDM Process scale and examined validity and reliability of the scale for attention-deficit/hyperactivity disorder (ADHD) treatment decisions. METHODS: Cross-sectional survey of caregivers (n = 498) of children (aged 5-13) diagnosed with ADHD, who had made a decision about ADHD medication in the last 2 years. Surveys included the adapted SDM Process scale (scores range 0-4, higher scores indicate more SDM), decisional conflict, decision regret, and decision involvement. Validity was assessed by testing hypothesized relationships between these constructs. A subset of participants was surveyed a week later to assess retest reliability. RESULTS: Pediatric Caregiver version of the SDM Process scale (M = 2.8, SD = 1.05) showed no evidence of floor or ceiling effects. The scale was found to be acceptable (<1% missing data) and reliable (intraclass correlation coefficient = 0.74). Scores demonstrated convergent validity, as they were higher for those without decisional conflict than those with decisional conflict (2.93 vs 2.46, P < .001, d = 0.46), and higher for caregivers who stated they made the decision with the provider than those who made the decision themselves (3.0 vs 2.7; P = .003). Higher scores were related to less regret (r = -0.15, P < .001), though the magnitude of the relationship was small. CONCLUSIONS: The adapted Pediatric Caregiver version of the SDM Process scale demonstrated acceptability, validity and reliability in the context of ADHD medication decisions made by caregivers of children 5-13. Scores indicate pediatricians generally involve caregivers in decision making about ADHD medication.

Activation of Tumor-Cell STING Primes NK-Cell Therapy.

Activation of the stimulator of interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding of the mechanism of action of STING agonists in human tumors is key to developing therapeutic combinations that activate effective innate antitumor immunity. Here, we report that malignant pleural mesothelioma cells robustly express STING and are responsive to STING agonist treatment ex vivo. Using dynamic single-cell RNA sequencing of explants treated with a STING agonist, we observed CXCR3 chemokine activation primarily in tumor cells and cancer-associated fibroblasts, as well as T-cell cytotoxicity. In contrast, primary natural killer (NK) cells resisted STING agonist-induced cytotoxicity. STING agonists enhanced migration and killing of NK cells and mesothelin-targeted chimeric antigen receptor (CAR)-NK cells, improving therapeutic activity in patient-derived organotypic tumor spheroids. These studies reveal the fundamental importance of using human tumor samples to assess innate and cellular immune therapies. By functionally profiling mesothelioma tumor explants with elevated STING expression in tumor cells, we uncovered distinct consequences of STING agonist treatment in humans that support testing combining STING agonists with NK and CAR-NK cell therapies.

Using Standardized Videos to Examine the Validity of the Shared Decision Making Process Scale: Results of a Randomized Online Experiment.

BACKGROUND: The Shared Decision Making (SDM) Process scale is a brief, patient-reported measure of SDM with demonstrated validity in surgical decision making studies. Herein we examine the validity of the scores in assessing SDM for cancer screening and medication decisions through standardized videos of good-quality and poor-quality SDM consultations. METHOD: An online sample was randomized to a clinical decision-colon cancer screening or high cholesterol-and a viewing order-good-quality video first or poor-quality video first. Participants watched both videos, completing a survey after each video. Surveys included the SDM Process scale and the 9-item SDM Questionnaire (SDM-Q-9); higher scores indicated greater SDM. Multilevel linear regressions identified if video, order, or their interaction predicted SDM Process scores. To identify how the SDM Process score classified videos, area under the curve (AUC) was calculated. The correlation between SDM Process score and SDM-Q-9 assessed construct validity. Heterogeneity analyses were conducted. RESULTS: In the sample of 388 participants (68% white, 70% female, average age 45 years) good-quality videos received higher SDM Process scores than poor-quality videos (Ps < 0.001), and those who viewed the good-quality high cholesterol video first tended to rate the videos higher. SDM Process scores were related to SDM-Q-9 scores (rs > 0.58; Ps < 0.001). AUC was poor (0.69) for the high cholesterol model and fair (0.79) for the colorectal cancer model. Heterogeneity analyses suggested individual differences were predictive of SDM Process scores. CONCLUSION: SDM Process scores showed good evidence of validity in a hypothetical scenario but were lacking in ability to classify good-quality or poor-quality videos accurately. Considerable heterogeneity of scoring existed, suggesting that individual differences played a role in evaluating good- or poor-quality SDM conversations.

Shared Decision-Making Is Associated with Better Outcomes in Patients with Knee But Not Hip Osteoarthritis: The DECIDE-OA Randomized Study.

BACKGROUND: Current guidelines recommend shared surgical decision-making, yet it is unclear whether shared decision-making improves health outcomes in patients who are considering knee and hip replacement. The purpose of the present study was to examine whether patients who made high-quality, informed, patient-centered (IPC) decisions had better health outcomes, higher satisfaction, and less decision regret compared with those who made lower-quality decisions. METHODS: A multisite, randomized study of 2 decision aids for patients with hip and knee osteoarthritis was utilized to collect data on decision-making and health outcomes at 2 time points: shortly after the initial surgical evaluation and about 6 months after treatment. We calculated the percentage of patients who made an IPC decision and examined the a priori hypotheses that IPC decisions would be associated with better health outcomes, satisfaction, and less regret at 6 months. Linear and logistic regression models were utilized to examine the relationships. RESULTS: The analytic sample included 854 patients with a mean age of 65 years (standard deviation, 9 years), of whom 58% were female, 93% were White non-Hispanic, 67% had knee (compared with hip) osteoarthritis, and 62% underwent operative treatment within 6 months of the initial evaluation. The majority of patients (68%) made IPC decisions. The IPC group had significantly larger gains in quality of life (mean difference in EuroQol-5 Dimension, 0.04; 95% confidence interval [CI], 0.02 to 0.07; p < 0.001) compared with the non-IPC group. For knee patients, the IPC group also had significantly better Knee injury and Osteoarthritis Outcome Scores (mean difference, 4.9; 95% CI, 1.5 to 8.3; p = 0.004), higher satisfaction (adjusted odds ratio [aOR], 1.7; 95% CI, 1.2 to 2.3; p = 0.003), much better pain relief (aOR, 2.1; 95% CI, 1.3 to 3.5; p = 0.002), and were more likely to have no decision regret (aOR, 2.3; 95% CI, 1.3 to 4.1; p = 0.003). For hip patients, IPC decisions were not associated with better Harris hip scores or satisfaction and were associated with more regret. CONCLUSIONS: Higher-quality decisions predicted small improvements in health outcomes, as well as greater satisfaction and less regret for patients with knee osteoarthritis, but not for patients with hip osteoarthritis. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Normal Ranges of Global Left Ventricular Myocardial Work Indices in Adults: A Meta-Analysis.

BACKGROUND: Recent studies have demonstrated that left ventricular myocardial work (MW) is incremental in diagnosis and prognostication compared with left ventricular ejection fraction and myocardial strain. The authors performed a meta-analysis of normal ranges of noninvasive MW indices including global work index, global constructive work, global wasted work, and global work efficiency and determined confounders that may contribute to variance in reported values. METHODS: Four databases (PubMed, Scopus, Embase, and the Cochrane Library) were searched through January 2021 using the key terms "myocardial work," "global constructive work," "global wasted work," "global work index," and "global work efficiency." Studies were included if the articles reported LV MW using two-dimensional transthoracic echocardiography in healthy normal subjects, either in a control group or comprising the entire study cohort. The weighted mean was estimated by using the random-effect model with a 95% CI. Heterogeneity across included studies was assessed using the I2 test. Funnel plots and the Egger regression test were used to assess potential publication bias. RESULTS: The search yielded 476 articles. After abstract and full-text screening, we included 13 data sets with 1,665 patients for the meta-analysis. The reported normal mean values of global work index and global constructive work among the studies were 2,010 mm Hg% (95% CI, 1,907-2,113 mm Hg%) and 2,278 mm Hg% (95% CI, 2,186-2,369 mm Hg%), respectively. Mean global wasted work was 80 mm Hg% (95% CI, 73-87 mm Hg%), and mean global work efficiency was 96.0% (95% CI, 96%-96%). Furthermore, gender significantly contributed to variations in normal values of global work index, global wasted work, and global work efficiency. No evidence of significant publication bias was observed. CONCLUSIONS: In this meta-analysis, the authors provide echocardiographic reference ranges for noninvasive indices of MW. These normal values could serve as a reference for clinical and research use.

Three-Dimensional Global Left Ventricular Myocardial Strain Reduced in All Directions in Subclinical Diabetic Cardiomyopathy: A Systematic Review and Meta-Analysis.

Background Three-dimensional (3D) speckle tracking echocardiography can identify subclinical diabetic cardiomyopathy without geometric assumption and loss of speckle from out-of-plane motions. There is, however, significant heterogeneity among the previous reports. We performed a systematic review and meta-analysis to compare 3D strain values between adults with asymptomatic, subclinical diabetes mellitus (ie, patients with diabetes mellitus without known clinical manifestations of cardiac disease) and healthy controls. Methods and Results After systematic review of 5 databases, 12 valid studies (544 patients with diabetes mellitus and 489 controls) were eligible for meta-analysis. Pooled means and mean difference (MD) using a random-effects model for 3D global longitudinal, circumferential, radial, and area strain were calculated. Patients with diabetes mellitus had an overall 2.31 percentage points lower 3D global longitudinal strain than healthy subjects (16.6%, 95% CI, 15.7-17.6 versus 19.0; 95% CI, 18.2-19.7; MD, -2.31, 95% CI, -2.72 to -2.03). Similarly, 3D global circumferential strain (18.9%; 95% CI, 17.5-20.3 versus 20.5; 95% CI, 18.9-22.1; MD, -1.50; 95% CI, -2.09 to -0.91); 3D global radial strain (44.6%; 95% CI, 40.2-49.1 versus 48.2; 95% CI, 44.7-51.8; MD, -3.47; 95% CI, -4.98 to -1.97), and 3D global area strain (30.5%; 95% CI, 29.2-31.8 versus 32.4; 95% CI, 30.5-34.3; MD, -1.76; 95% CI, -2.74 to -0.78) were also lower in patients with diabetes mellitus. Significant heterogeneity was noted between studies for all strain directions (inconsistency factor [I2], 37%-78%). Meta-regression in subgroup analysis of studies using the most popular vendor found higher prevalence of hypertension as a significant contributor to worse 3D global longitudinal strain. Higher hemoglobulin A1c was the most significant contributor to worse 3D global circumferential strain in patients with diabetes mellitus. Conclusions Three-dimensional myocardial strain was reduced in all directions in asymptomatic diabetic patients. Hypertension and hemoglobin A1c were associated with worse 3D global longitudinal strain and 3D global circumferential strain, respectively. Registration URL: https://www.crd.york.ac.uk/prospero; unique identifier: CRD42020197825.

Development of a Good Clinical Practice inspection checklist to assess clinical trial sites in Vietnam.

BACKGROUND: Assessing the capacity of a healthcare institution to conduct and manage clinical research studies is challenging, especially in developing countries where resources are limited. The objective of this study was to develop a practical and transparent tool for the Vietnam Ministry of Health (MOH) to assess institutions' capacity to lead clinical trials in line with local and international regulations. METHODS: We reviewed the literature, relevant official international and national guidelines, regulations and checklists for clinical sites' assessment to identify key indicators of clinical research capacity. We developed a Good Clinical Practice (GCP) inspection checklist consisting of a questionnaire with 30 key criteria, including 16 core criteria and 14 recommended criteria, related to four central aspects of clinical research management (ie, governance, operations, infrastructures and human resources). Following a detailed review and assessment by a panel of experts, sponsors and academic investigators, we assessed the checklist's applicability in a pilot study involving 10 sites with various clinical research experiences. RESULTS: Independently of their clinical research experience, all participating institutions fulfilled most of the core criteria. In contrast, a significant variability was observed in the compliance to recommended capacity criteria, especially those related to governance (certifications and reporting) as well as operations (existence of a clinical research coordination unit or electronic trial management system). CONCLUSIONS: A GCP inspection checklist was successfully developed to support the MOH in the assessment of institutions' capacity to conduct clinical research. Additional efforts from all stakeholders are now warranted to provide local sites with sustainable capacity development resources that will further build up and harmonise Vietnamese clinical research settings.

Are We Improving? Update and Critical Appraisal of the Reporting of Decision Process and Quality Measures in Trials Evaluating Patient Decision Aids.

BACKGROUND: In 2014, a systematic review found large gaps in the quality of reporting of measures used in 86 published trials evaluating the effectiveness of patient decision aids (PtDAs). The purpose of this study was to update that review. METHODS: We examined measures of decision making used in 49 randomized controlled trials included in the 2014 and 2017 Cochrane Collaboration systematic review of PtDAs. Data on development of the measures, reliability, validity, responsiveness, precision, interpretability, feasibility, and acceptability were independently abstracted by 2 paired reviewers. RESULTS: Information from 273 measures was abstracted, and 109 of these covered the core domains of decision processes (n = 55) and decision quality including informed choice/knowledge (n = 48) and values-choice concordance (n = 12). Very few studies reported data on the performance and clinical sensibility of measures, with reliability (23%) and validity (6%) being the most common. Studies using new measures were less likely to include information about their psychometric performance compared with previously published measures. LIMITATIONS: The review was limited to reporting of measures in studies included in the Cochrane review and did not consult prior publications. CONCLUSION: There continues to be very little reported about the development or performance of measures used to evaluate the effectiveness of PtDAs in published trials. Minimum reporting standards have been published, and efforts to require investigators to use them are needed.

CLEO: a multidimensional tool to assess clinical, economic and organisational impacts of pharmacists' interventions.

OBJECTIVES: Clinical pharmacists' interventions (PIs) are an important element in ensuring good pharmaceutical care. We aimed to develop and validate a comprehensive multidimensional tool for assessing the potential impact of PIs for daily practice of medication review. METHODS: Experts of the French Society of Clinical Pharmacy (SFPC) developed the CLinical, Economic and Organisational (CLEO) tool, consisting of three independent dimensions concerning clinical, economic and organisational impact. They were asked to analyse 30 scenarios of PIs, and re-rated 10 PIs with a washout of 1 month (internal validation). Then, seven external experts not involved in the development of the tool rated 60 scenarios collected when using the CLEO in daily practice. Inter- and intra-rater reliabilities were determined by calculation of the intra-class correlation (ICCA,1). Users' satisfaction and acceptability of the tool were assessed on a 7-level Likert scale with a 17-item questionnaire. RESULTS: For internal reliability, the inter-rater reliability for the CLEO tool was good for clinical dimensions (ICCA,1=0.693), excellent for economic dimensions (ICCA,1=0.815) and fair for organisational dimensions (ICCA,1=0.421); and the intra-rater reliability was good for clinical dimensions (ICCA,1=0.822), excellent for economic dimensions (ICCA,1=0.918) and good for organisational dimensions (ICCA,1=0.738). For external reliability, the inter-rater reliability was good for clinical dimensions (ICCA,1=0.649), excellent for economic dimensions (ICCA,1=0.814) and fair for organisational dimensions (ICCA,1=0.500). CLEO was viewed as relevant (mean±SD 4.93±1.27), acceptable (4.81±1.78), practicable (5.56±1.45) and precise (5.38±1.47). CONCLUSIONS: CLEO is a comprehensive tool assessing clinical, economic and organisational impacts of PIs which has been developed, validated and was reliable and feasible for use in routine clinical practice.

Validation of the Impact Index: can we measure disease effects on quality of life in patients with hip and knee osteoarthritis?

PURPOSE: To validate the Impact Index, a short, publicly available scale that measures the extent to which a respondent's health problem adversely impacts their quality of life. METHODS: Secondary analysis of patients with hip or knee osteoarthritis surveyed after visiting a surgeon at baseline (N = 322) and about 6 months after the visit (N = 283). Patients responded to the Impact Index and previously validated questionnaires about overall health, pain, and function. The Impact Index includes four questions that ask how much the respondent is bothered, worried, limited, or in pain due to their health condition over the past 30 days. Total scores range from 0 to 12; higher scores indicate more deleterious impact. RESULTS: Patients were mostly female (55%), majority white (95%), had an average age of 65 (SD = 9), and most had surgery (64%). The baseline Impact Index score was 9.48 (SD = 2.63); at follow up 4.75 (SD = 3.54). Impact Index was related to overall health at baseline (r = - 0.49). For knee patients at baseline, Impact Index was negatively related to their knee symptoms (r = - 0.49) and knee pain (r = - 0.67). For hip patients at baseline, Impact Index was negatively related to the Harris Hip score (r = - 0.62). Scale directions varied; however, the signs of all correlations were as hypothesized. The Impact Index was predictive of surgical choice (p < .001, OR = 1.45), however, overall health (p = .88) and comorbidity (p = .24) measures were not. Reliability was acceptable (α = 0.85). Responsiveness statistics suggested overall health, pain, function, and Impact Index measures reflected improvement patients experienced from surgery. The Impact Index had the largest effect sizes (> - 3.4) and Guyatt Responsiveness Statistics (> - 2.3). CONCLUSIONS: The Impact Index demonstrated strong evidence of validity, reliability, and responsiveness in hip or knee osteoarthritis patients.