A systematic review on experimental studies about patient adherence to treatment.

A better understanding of patients' adherence to treatment is a prerequisite to maximize the benefit of healthcare provision for patients, reduce treatment costs, and is a key factor in a variety of subsequent health outcomes. We aim to understand the state of the art of scientific evidence about which factors influence patients' adherence to treatment. A systematic literature review was conducted using PRISMA guidelines in five separate electronic databases of scientific publications: PubMed, PsycINFO (ProQuest), Cochrane library (Ovid), Google Scholar, and Web of Science. The search focused on literature reporting the significance of factors in adherence to treatment between 2011 and 2021, including only experimental studies (e.g., randomized controlled trials [RCT], clinical trials, etc.). We included 47 experimental studies. The results of the systematic review (SR) are grouped according to predetermined categories of the World Health Organization (WHO): socioeconomic, treatment, condition, personal, and healthcare-related factors. This review gives an actual overview of evidence-based studies on adherence and analyzed the significance of factors defined by the WHO classification. By showing the strength of certain factors in several independent studies and concomitantly uncovering gaps in research, these insights could serve as a basis for the design of future adherence studies and models.

Differences in healthcare service utilization in patients with polypharmacy according to their risk level by adjusted morbidity groups: a population-based cross-sectional study.

BACKGROUND: Patients with polypharmacy suffer from complex medical conditions involving a large healthcare burden. This study aimed to describe the characteristics and utilization of primary care (PC) and hospital care (HC) and factors associated in chronic patients with polypharmacy, stratifying by adjusted morbidity groups (AMG) risk level, sex and age, and comparing with non-polypharmacy. METHODS: Cross-sectional study conducted in a Spanish basic healthcare area. Studied patients were those over 18 years with chronic diseases identified by the AMG tool from Madrid electronic clinical record, which was the data source. Sociodemographic, sociofunctional, clinical and healthcare utilization variables were described and compared by risk level, sex, age and having or not polypharmacy. Factors associated with healthcare utilization in polypharmacy patients were determined by a negative binomial regression model. RESULTS: In the area studied, 61.3% patients had chronic diseases, of which 16.9% had polypharmacy vs. 83.1% without polypharmacy. Patients with polypharmacy (vs. non-polypharmacy) mean age was 82.7 (vs. 52.7), 68.9% (vs. 60.7%) were women, and 22.0% (vs. 1.2%) high risk. Their average number of chronic diseases was 4.8 (vs. 2.2), and 95.6% (vs. 56.9%) had multimorbidity. Their mean number of annual healthcare contacts was 30.3 (vs. 10.5), 25.9 (vs. 8.8) with PC and 4.4 (vs. 1.7) with HC. Factors associated with a greater PC utilization in patients with polypharmacy were elevated complexity, high risk level and dysrhythmia. Variables associated with a higher HC utilization were also increased complexity and high risk, in addition to male sex, being in palliative care, having a primary caregiver, suffering from neoplasia (specifically lymphoma or leukaemia) and arthritis, whereas older age and immobilization were negatively associated. CONCLUSIONS: Polypharmacy population compared to non-polypharmacy was characterized by a more advanced age, predominance of women, high-risk, complexity, numerous comorbidities, dependency and remarkable healthcare utilization. These findings could help healthcare policy makers to optimize the distribution of resources and professionals within PC and HC systems, aiming for the improvement of polypharmacy management and rational use of medicines while reducing costs attributed to healthcare utilization by these patients.

An Implantable Wireless Inductive Sensor System Designed to Monitor Prosthesis Motion in Total Joint Replacement Surgery.

Currently, the most common method for detecting prosthetic implant loosening is imaging. Unfortunately, imaging methods are imprecise in detecting the early signs of implant loosening. This paper describes a new wireless inductive proximity sensor system for detecting early implant loosening. The loosening of the implant is accurately detected by analyzing the electromagnetic field generated by the passive sensors located around the implant. The sensor system was modeled and simulated using COMSOL, and then tested experimentally. The inductive proximity sensor and the metallic implant form a coupled circuit is tuned to oscillate at a designed frequency. The circuit's integrated controller measures and records specific sensor's parameters such as resistance and inductance of the sensor that are directly related to the distance between the sensor system and the implant. A prototype has been developed and the results show that the designed proximity sensor is capable of measuring the loosening of the hip implant at [Formula: see text]m resolution at distances of less than [Formula: see text], and of [Formula: see text]m resolution at a distance of [Formula: see text]. Furthermore, there is a good correlation between the simulated and experimental results.

Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function.

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects.

Role of salivary and candidal proteins in denture stomatitis: an exploratory proteomic analysis.

Denture stomatitis, inflammation and redness beneath a denture, affects nearly half of all denture wearers. Candidal organisms, the presence of a denture, saliva, and host immunity are the key etiological factors for the condition. The role of salivary proteins in denture stomatitis is not clear. In this study 30 edentulous subjects wearing a maxillary complete denture were recruited. Unstimulated whole saliva from each subject was collected and pooled into two groups (n = 15 each), healthy and stomatitis (Newton classification II and III). Label-free multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) proteomics on two mass spectrometry platforms were used to determine peptide mass differences between control and stomatitis groups. Cluster analysis and principal component analysis were used to determine the differential expression among the groups. The two proteomic platforms identified 97 and 176 proteins (ANOVA; p < 0.01) differentially expressed among the healthy, type 2 and 3 stomatitis groups. Three proteins including carbonic anhydrase 6, cystatin C, and cystatin SN were found to be the same as previous study. Salivary proteomic profiles of patients with denture stomatitis were found to be uniquely different from controls. Analysis of protein components suggests that certain salivary proteins may predispose some patients to denture stomatitis while others are believed to be involved in the reaction to fungal infection. Analysis of candidal proteins suggests that multiple species of candidal organisms play a role in denture stomatitis.

Systems biology and proteomic analysis of cerebral cavernous malformation.

UNLABELLED: Cerebral cavernous malformations (CCM) are vascular anomalies caused by mutations in genes encoding KRIT1, OSM and PDCD10 proteins causing hemorrhagic stroke. We examine proteomic change of loss of CCM gene expression. Using human umbilical vein endothelial cells, label-free differential protein expression analysis with multidimensional liquid chromatography/tandem mass spectrometry was applied to three CCM protein knockdown cell lines and two control cell lines: ProteomeXchange identifier PXD000362. Principle component and cluster analyses were used to examine the differentially expressed proteins associated with CCM. The results from the five cell lines revealed 290 and 192 differentially expressed proteins (p < 0.005 and p < 0.001, respectively). Most commonly affected proteins were cytoskeleton-associated proteins, in particular myosin-9. Canonical genetic pathway analysis suggests that CCM may be a result of defective cell-cell interaction through dysregulation of cytoskeletal associated proteins. CONCLUSION: The work explores signaling pathways that may elucidate early detection and novel therapy for CCM.

Role of cytoskeletal proteins in cerebral cavernous malformation signaling pathways: a proteomic analysis.

Three genetic mutations were found to cause cerebral cavernous malformation (CCM), a vascular anomaly predisposing affected individuals to hemorrhagic stroke. These CCM proteins function together as a protein complex in the cell. Loss of expression of each CCM gene results in loss of in vitro endothelial tube formation. Label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) was applied to explore the proteomic profile for loss of each CCM gene expression in mouse endothelial stem cells (MEES) compared to mock shRNA and no shRNA control cell-lines. Differentially expressed proteins were identified (p < 0.05). 120 proteins were differentially expressed among the cell-lines. Principal component analysis and cluster analysis show the effects of individual knockdown. In all knockdown cell-lines, altered expression of cytoskeletal proteins is the most common. While all CCM mutations result in similar pathology, different CCM mutations have their own distinct pathogenesis in cell signaling.

Salivary proteins associated with hyperglycemia in diabetes: a proteomic analysis.

Effective monitoring of glucose levels is necessary for patients to achieve greater control over their diabetes. However, only about a quarter of subjects with diabetes who requires close serum glucose monitoring, regularly check their serum glucose daily. One of the potential barriers to patient compliance is the blood sampling requirement. Saliva and its protein contents can be altered in subjects with diabetes, possibly due to changes in glycemic control. We propose here that salivary proteomes of subjects with diabetes may be different based on their glycemic control as reflected in A1C levels. A total of 153 subjects with type 1 or 2 diabetes were recruited. Subjects in each type of diabetes were divided into 5 groups based on their A1C levels; <7, 7-8, 8-9, 9-10, >10. To examine the global proteomic changes associated with A1C, the proteomic profiling of pooled saliva samples from each group was created using label-free quantitative proteomics. Similar proteomic analysis for individual subjects (N=4, for each group) were then applied to examine proteins that may be less abundant in pooled samples. Principle component analysis (PCA) and cluster analysis (p<0.01 and p<0.001) were used to define the proteomic differences. We, therefore, defined the salivary proteomic changes associated with A1C changes. This study demonstrates that differences exist between salivary proteomic profiles in subjects with diabetes based on the A1C levels.

Postdischarge pharmacist medication reconciliation: impact on readmission rates and financial savings.

OBJECTIVE: To assess the impact of ambulatory clinical pharmacist medication therapy assessment and reconciliation for patients postdischarge in terms of hospital readmission rates, financial savings, and medication discrepancies. SETTING: Group Health Cooperative (Group Health) in Washington State, from September 2009 through February 2010. PRACTICE DESCRIPTION: Group Health is a nonprofit integrated group practice and health plan, operating 25 primary care medical centers and 5 specialty centers. Group Health's practice design is a patient-centered medical home model. PRACTICE INNOVATION: All patients identified as high risk for readmission were followed by Group Health care management. Patients in care management who received a phone call from a pharmacist 3 to 7 days postdischarge for medication therapy assessment and reconciliation were identified as the medication review group (n = 243). Patients who did not receive clinical pharmacist intervention were included in the comparison group (n = 251). MAIN OUTCOME MEASURES: Readmission rates, financial savings, and medication discrepancies. RESULTS: Patients who received medication therapy assessment and reconciliation had decreased readmission rates at 7, 14, and 30 days postdischarge, with statistical significance at 7 and 14 days. Medication review versus comparison readmission rates were as follows: 7 days: 0.8% vs. 4% ( P = 0.01); 14 days: 5% vs. 9% ( P = 0.04); and 30 days: 12% vs. 14% ( P = 0.29). Financial savings for Group Health per 100 patients who received medication reconciliation was an estimated $35,000, translating to more than $1,500,000 in savings annually. Of patients, 80% had at least one medication discrepancy upon discharge. CONCLUSION: Most literature on medication reconciliation evaluates inpatient processes, whereas data on medication reconciliation postdischarge are limited. Our data support the hypothesis that medication assessment and reconciliation by pharmacists 3 to 7 days postdischarge can decrease readmissions and provide cost savings.

Elucidating role of salivary proteins in denture stomatitis using a proteomic approach.

Denture stomatitis (DS) is the most common oral pathology among denture wearers, affecting over one-third of this group. DS is usually associated with C. albicans. However, unlike other oral candidiasis, most DS patients have intact host immunity. The presence of a denture alone is usually sufficient for DS. Saliva and its protein contents can theoretically predispose some denture wearers to DS and others resistant toward DS. Here we proposed for the first time to define salivary proteomic profiles of denture wearers with and without DS. SELDI-TOF/MS analysis suggests that there is a proteomic differentiation among control, localized and generalized DS. Based on initial SELDI-TOF/MS profiling, we further used reversed phase liquid chromatography, MALDI-TOF/MS, and LC-MS/MS to characterize the salivary proteins associated with DS. Nineteen proteins based on SELDI-TOF/MS profiling were found including cystatin-SN, statherin, kininogen-1, desmocollin-2, carbonic anhydrase-6, peptidyl-prolyl cis-trans isomerase A like peptides, cystatin C, and several immunoglobulin fragments. The proteomic content gives evidence of the interaction between host tissue, saliva, and candida. Further examination in larger populations of these proteins may help to gain a better understanding of DS pathological processes and improve DS treatments.

Exploring salivary proteomes in edentulous patients with type 2 diabetes.

Type 2 diabetes and tooth loss are linked both epidemiologically and pathophysiologically. We applied label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) to explore the proteomic profile of saliva samples collected from selected type 2 diabetic edentulous patients and non-diabetic controls. Ninety-six peptides corresponding to 52 proteins were differentially expressed between the diabetic edentulous patients and controls (p < 0.05). Some diabetes-related inflammatory biomarkers including glyceraldehyde-3-phosphate dehydrogenase and serum amyloid A were detected with levels increased in diabetic samples. Other biomarkers including amylase, palate, lung and nasal epithelium associated protein (PLUNC), and serotransferrin levels were decreased in diabetic samples. In contrast with previous findings, salivary carbonic anhydrase 6 and alpha-2 macroglobulin levels, however, were decreased in this diabetic patient population. Cluster analysis and principle component analysis demonstrated a differential pattern of protein biomarker expression between diabetic and control subjects. Western blot analysis was completed to confirm the relatively lower expression level of two biomarkers, including PLUNC and amylase in the diabetic group compared to control subjects. The presence of salivary biomarkers specific for diabetes in edentulous subjects mimics those in serum, especially those related to inflammatory/lipid metabolism. While this exploratory study requires further validation with a larger population, it provides proof-of-principle for salivary proteomics for edentulous subjects with diabetes.

Accuracy of blood pressure measurements reported in an electronic medical record during routine primary care visits.

Electronic medical records (EMRs) allow for real-time access to blood pressure (BP) information on a population basis and improve identification and treatment of individuals with hypertension. Despite the potential uses of the data available from EMRs, relatively little research has examined the reliability of this data. To address this gap, the authors examined the reliability of BP taken at primary care visits and recorded in an EMR with those taken at a research study visit at which standard protocols were used to measure BP among all adults as well as by sex and age. Systolic BP (SBP) averaged 3.7 (17.3) points and diastolic BP (DBP) was 2.8 (10.6) points lower in the EMR than in the study visit across age and sex groups, with all differences statistically significant. For this cohort of patients with a diagnosis of hypertension, there was moderate correlation between BP measurements taken in clinic and at research. However, BP control for individuals, as defined by an SBP <140 mm Hg and DBP 90 mm Hg, differed by almost 25%. Known variability of BP and clinic procedures for measuring and recording BP may account for these differences.

The impact of a diagnostic reminder system on student clinical reasoning during simulated case studies.

INTRODUCTION: Diagnostic reminder systems (DRS) may help students improve their clinical reasoning skill and gain competency in using informatics tools. This study explored the influence of Isabel PRO, a web-based DRS, on student diagnostic reasoning during simulated encounters. METHODS: Diagnostic reasoning was assessed in 20 fourth-year medical students during four simulated case scenarios. After seeing each case, students submitted diagnostic hypotheses before (Pre-Isabel) and after (Post-Isabel) using Isabel PRO. The quality of the Pre- and Post-Isabel diagnostic hypotheses was assessed and compared to determine the impact of a DRS on student diagnostic reasoning. A follow-up survey and focus group identified student perception toward the use of a DRS in educational settings. RESULTS: Paired t testing demonstrated that diagnostic accuracy significantly improved after using Isabel PRO (P < 0.05). Students found the software relatively simple to learn, felt that it helped them reflect on diagnostic options that they had not originally considered, and valued the opportunity to use the software in conjunction with simulated cases. CONCLUSIONS: Despite limited experience, students were able to effectively use a DRS to improve their diagnostic accuracy. Use of a DRS within the context of a patient case represents a distinct clinical skill set requiring appropriate training. Providing learners with gold standard examples of how to best use a specific informatics tool within specific clinical situations is an essential learning component. Simulated case scenarios offer an appropriate platform for introducing diagnostic support tools to learners within a clinical context.

Simulation-based examinations in physician assistant education: A comparison of two standard-setting methods.

PURPOSE: this study explored the reliability of two simple standard-setting methods that are used to set passing standards for a standardized patient (SP) exam in physician assistant (PA) education. METHODS: fifty-four second-year PA students participated in a multistation SP-based clinical skills exam. Cut scores were set using the Angoff and Borderline Group methods. A panel of PA faculty set cut scores using the Angoff method. A modified version of the Borderline Group method set cut scores using SP global ratings verified by faculty review. Inter-rater reliability between judges was evaluated using kappa coefficient (k) for the Angoff method and intraclass correlation coefficient (ICC) for the Borderline Group method. RESULTS: the Borderline Group method set an overall cut score for the exam of 76% (95% CI +/- 5) and the Angoff method set a cut score at 62% (95% CI +/- 9). Both methods demonstrated sufficient inter-rater reliability (k 0.60, ICC > 0.70; both significant at p < 0.05), although one case (preop history and physical) demonstrated poor inter-rater reliability between judges using the Borderline Group method. DISCUSSION: the Borderline Group method offered a slightly more reliable cut score when compared to the standard set by the Angoff method, but was more challenging to implement. In addition, one case demonstrated poor inter-rater reliability with the Borderline Group method. Using SPs to complete global borderline ratings offers one solution to make the Borderline Group method more feasibile, but requires a high degree of initial rater calibration and periodic measures of interrater reliability between faculty and SPs.

The impact of leadership and team behavior on standard of care delivered during human patient simulation: a pilot study for undergraduate medical students.

BACKGROUND: Methodology to train team behavior during simulation has received increased attention, but standard performance measures are lacking, especially at the undergraduate level. PURPOSES: Our purposes were to develop a reliable team behavior measurement tool and explore the relationship between team behavior and the delivery of an appropriate standard of care specific to the simulated case. METHODS: Authors developed a unique team measurement tool based on previous work. Trainees participated in a simulated event involving the presentation of acute dyspnea. Performance was rated by separate raters using the team behavior measurement tool. Interrater reliability was assessed. The relationship between team behavior and the standard of care delivered was explored. RESULTS: The instrument proved to be reliable for this case and group of raters. Team behaviors had a positive relationship with the standard of medical care delivered specific to the simulated case. CONCLUSIONS: The methods used provide a possible method for training and assessing team performance during simulation.

Electronic communications and home blood pressure monitoring (e-BP) study: design, delivery, and evaluation framework.

BACKGROUND: Randomized controlled trials have provided unequivocal evidence that treatment of hypertension decreases mortality and major disability from cardiovascular disease; however, blood pressure remains inadequately treated in most affected individuals. This large gap continues despite the facts that more than 90% of adults with hypertension have health insurance, and hypertension is the leading cause of visits to the doctor. New approaches are needed to improve hypertension care. OBJECTIVES: The Electronic Communications and Home Blood Pressure Monitoring (e-BP) study is a three-arm randomized controlled trial designed to determine whether care based on the Chronic Care Model and delivered over the Internet improves hypertension care. The primary study outcomes are systolic, diastolic, and blood pressure control; secondary outcomes are medication adherence, patient self-efficacy, satisfaction and quality of life, and healthcare utilization and costs. METHODS: Hypertensive patients receiving care at Group Health medical centers are eligible if they have uncontrolled blood pressure on two screening visits and access to the Web and an e-mail address. Study participants are randomly assigned to three intervention groups: (a) usual care; (b) home blood pressure monitoring receipt and proficiency training on its use and the Group Health secure patient website (with secure e-mail access to their healthcare provider, access to a shared medical record, prescription refill and other services); or (c) this plus pharmacist care management (collaborative care management between the patient, the pharmacist, and the patient's physician via a secure patient website and the electronic medical record). CONCLUSION: We will determine whether a new model of patient-centered care that leverages Web communications, self-monitoring, and collaborative care management improves hypertension control. If this model proves successful and cost-effective, similar interventions could be used to improve the care of large numbers of patients with uncontrolled hypertension.