Rate of sepsis hospitalizations after misdiagnosis in adult emergency department patients: a look-forward analysis with administrative claims data using Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) methodology in an integrated health system.

OBJECTIVES: Delays in sepsis diagnosis can increase morbidity and mortality. Previously, we performed a Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) "look-back" analysis to identify symptoms at risk for delayed sepsis diagnosis. We found treat-and-release emergency department (ED) encounters for fluid and electrolyte disorders (FED) and altered mental status (AMS) were associated with downstream sepsis hospitalizations. In this "look-forward" analysis, we measure the potential misdiagnosis-related harm rate for sepsis among patients with these symptoms. METHODS: Retrospective cohort study using electronic health record and claims data from Kaiser Permanente Mid-Atlantic States (2013-2018). Patients ≥18 years with ≥1 treat-and-release ED encounter for FED or AMS were included. Observed greater than expected sepsis hospitalizations within 30 days of ED treat-and-release encounters were considered potential misdiagnosis-related harms. Temporal analyses were employed to differentiate case and comparison (superficial injury/contusion ED encounters) cohorts. RESULTS: There were 4,549 treat-and-release ED encounters for FED or AMS, 26 associated with a sepsis hospitalization in the next 30 days. The observed (0.57%) minus expected (0.13%) harm rate was 0.44% (absolute) and 4.5-fold increased over expected (relative). There was a spike in sepsis hospitalizations in the week following FED/AMS ED visits. There were fewer sepsis hospitalizations and no spike in admissions in the week following superficial injury/contusion ED visits. Potentially misdiagnosed patients were older and more medically complex. CONCLUSIONS: Potential misdiagnosis-related harms from sepsis are infrequent but measurable using SPADE. This look-forward analysis validated our previous look-back study, demonstrating the SPADE approach can be used to study infectious disease syndromes.

Effectiveness of a pathway-driven eHealth-based integrated care model (PEICM) for community-based hypertension management in China: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of hypertension is high and increasing in China in recent years. The treatment and control of hypertension calls for long-term management beyond hospital, which is hard to implement in traditional care settings. Integrated care combined with information technology can promote high-quality healthcare services across the life-course. However, few studies have applied a customized integrated care model in community-based hypertension management in China, catering to the emerging "three-manager" mode. This study aims to identify the effectiveness of a pathway-driven eHealth-based integrated model that implemented as a full-featured telehealth system to facilitate standardized management of hypertension in China. METHODS: The trial has been designed as a 1-year, non-blinded superiority trial with two parallel groups. A total of 402 hypertensive patients who meet the eligibility criteria will be recruited and randomized with a 1:1 allocation. All the participants will receive a mobile device for self-management, which is a part of our telehealth system. Participants in the control group will only use the device for BP measurement and receive regular follow-ups from care providers according to the guidelines. Participants in the intervention group will gain full access to the system and receive intervention based on the proposed model (a well-designed coordinated care pathway consisting of 9 tasks). Outcomes will be measured mainly on three occasions (at inclusion, at 6 months, and at 12 months). The primary outcome is mean change in systolic blood pressure over a 12-month period. Secondary outcomes include changes in diastolic blood pressure, biochemical indexes related to hypertension, lifestyles, self-management adherence, and hypertension awareness, as well as work efficiency of care providers. DISCUSSION: This study aims to investigate whether a pathway-driven eHealth-based integrated care model based on the "three-manager" mode will improve hypertension control in China. Success of the model would help improve the quality of present community-based management procedures and benefit more patients with uncontrolled hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027645 . Registered on November 22, 2019.

Missed acute myocardial infarction in the emergency department-standardizing measurement of misdiagnosis-related harms using the SPADE method.

OBJECTIVES: Diagnostic error is a serious public health problem. Measuring diagnostic performance remains elusive. We sought to measure misdiagnosis-related harms following missed acute myocardial infarctions (AMI) in the emergency department (ED) using the symptom-disease pair analysis of diagnostic error (SPADE) method. METHODS: Retrospective administrative data analysis (2009-2017) from a single, integrated health system using International Classification of Diseases (ICD) coded discharge diagnoses. We looked back 30 days from AMI hospitalizations for antecedent ED treat-and-release visits to identify symptoms linked to probable missed AMI (observed > expected). We then looked forward from these ED discharge diagnoses to identify symptom-disease pair misdiagnosis-related harms (AMI hospitalizations within 30-days, representing diagnostic adverse events). RESULTS: A total of 44,473 AMI hospitalizations were associated with 2,874 treat-and-release ED visits in the prior 30 days. The top plausibly-related ED discharge diagnoses were "chest pain" and "dyspnea" with excess treat-and-release visit rates of 9.8% (95% CI 8.5-11.2%) and 3.4% (95% CI 2.7-4.2%), respectively. These represented 574 probable missed AMIs resulting in hospitalization (adverse event rate per AMI 1.3%, 95% CI 1.2-1.4%). Looking forward, 325,088 chest pain or dyspnea ED discharges were followed by 508 AMI hospitalizations (adverse event rate per symptom discharge 0.2%, 95% CI 0.1-0.2%). CONCLUSIONS: The SPADE method precisely quantifies misdiagnosis-related harms from missed AMIs using administrative data. This approach could facilitate future assessment of diagnostic performance across health systems. These results correspond to ∼10,000 potentially-preventable harms annually in the US. However, relatively low error and adverse event rates may pose challenges to reducing harms for this ED symptom-disease pair.

Polydopamine-Mesoporous Silica Core-Shell Nanoparticles for Combined Photothermal Immunotherapy.

Cancer immunotherapy involves a cascade of events that ultimately leads to cytotoxic immune cells effectively identifying and destroying cancer cells. Responsive nanomaterials, which enable spatiotemporal orchestration of various immunological events for mounting a highly potent and long-lasting antitumor immune response, are an attractive platform to overcome challenges associated with existing cancer immunotherapies. Here, we report a multifunctional near-infrared (NIR)-responsive core-shell nanoparticle, which enables (i) photothermal ablation of cancer cells for generating tumor-associated antigen (TAA) and (ii) triggered release of an immunomodulatory drug (gardiquimod) for starting a series of immunological events. The core of these nanostructures is composed of a polydopamine nanoparticle, which serves as a photothermal agent, and the shell is made of mesoporous silica, which serves as a drug carrier. We employed a phase-change material as a gatekeeper to achieve concurrent release of both TAA and adjuvant, thus efficiently activating the antigen-presenting cells. Photothermal immunotherapy enabled by these nanostructures resulted in regression of primary tumor and significantly improved inhibition of secondary tumor in a mouse melanoma model. These biocompatible, biodegradable, and NIR-responsive core-shell nanostructures simultaneously deliver payload and cause photothermal ablation of the cancer cells. Our results demonstrate potential of responsive nanomaterials in generating highly synergistic photothermal immunotherapeutic response.

A precise and accurate acupoint location obtained on the face using consistency matrix pointwise fusion method.

OBJECTIVE: To develop a more precise and accurate method, and identified a procedure to measure whether an acupoint had been correctly located. METHODS: On the face, we used an acupoint location from different acupuncture experts and obtained the most precise and accurate values of acupoint location based on the consistency information fusion algorithm, through a virtual simulation of the facial orientation coordinate system. RESULTS: Because of inconsistencies in each acupuncture expert's original data, the system error the general weight calculation. First, we corrected each expert of acupoint location system error itself, to obtain a rational quantification for each expert of acupuncture and moxibustion acupoint location consistent support degree, to obtain pointwise variable precision fusion results, to put every expert's acupuncture acupoint location fusion error enhanced to pointwise variable precision. Then, we more effectively used the measured characteristics of different acupuncture expert's acupoint location, to improve the measurement information utilization efficiency and acupuncture acupoint location precision and accuracy. CONCLUSION: Based on using the consistency matrix pointwise fusion method on the acupuncture experts' acupoint location values, each expert's acupoint location information could be calculated, and the most precise and accurate values of each expert's acupoint location could be obtained.

Random effects models for assessing diagnostic accuracy of traditional Chinese doctors in absence of a gold standard.

Two common problems in assessing the accuracy of traditional Chinese medicine (TCM) doctors in detecting a particular symptom are the unknown true symptom status and the ordinal-scale of the symptom status. Wang et al. (Biostatistics 2011; DOI: 10.1093/biostatistics/kxq075) proposed a nonparametric maximum likelihood method for estimating the accuracy of different TCM doctors without a gold standard when the true symptom status is measured on an ordinal-scale. A key assumption of their work is that the diagnosis results are independent conditional on the gold standard. This assumption can be violated in many practical situations.In this paper, we propose a random effects modeling approach that extends their method to incorporate dependence structure among different tests or doctors. The proposed method is illustrated on a real data set from TCM, which contains the diagnostic results from five doctors for the same patients regarding symptoms related to Chills disease. The same data set was analyzed by Wang et al. under the conditional independence assumption. In addition, we also discuss an ad hoc test for the model fitting and a likelihood ratio test on the random effects.

Evaluation of diagnostic accuracy in detecting ordered symptom statuses without a gold standard.

Our research is motivated by 2 methodological problems in assessing diagnostic accuracy of traditional Chinese medicine (TCM) doctors in detecting a particular symptom whose true status has an ordinal scale and is unknown-imperfect gold standard bias and ordinal scale symptom status. In this paper, we proposed a nonparametric maximum likelihood method for estimating and comparing the accuracy of different doctors in detecting a particular symptom without a gold standard when the true symptom status had an ordered multiple class. In addition, we extended the concept of the area under the receiver operating characteristic curve to a hyper-dimensional overall accuracy for diagnostic accuracy and alternative graphs for displaying a visual result. The simulation studies showed that the proposed method had good performance in terms of bias and mean squared error. Finally, we applied our method to our motivating example on assessing the diagnostic abilities of 5 TCM doctors in detecting symptoms related to Chills disease.

The effect of seal oil on paclitaxel induced cytotoxicity and apoptosis in breast carcinoma MCF-7 and MDA-MB-231 cell lines.

Some studies have suggested that omega-3 polyunsaturated fatty acids (PUFAs) have an inhibitory effect on the growth of cancer cells and therefore have the potential to increase the efficacy of cancer chemotherapeutic drugs. Considering that omega-3 PUFAs are present abundantly in harp seal oil, we investigated the effect of seal oil on the cytotoxicity and apoptosis induced by paclitaxel in 2 breast cancer cell lines, MCF-7 and MDA-MB-231, respectively. Cytotoxicity evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the concentration of paclitaxel that is required for 50% inhibition of cell growth in the presence of seal oil was significantly lower than that of paclitaxel alone. Apoptosis assessment based on morphological changes and DNA fragmentation results indicated that more cells treated with paclitaxel in combination with seal oil underwent apoptosis than with paclitaxel alone. Western blot analysis showed that the expression of B cell lymphoma-2 (Bcl-2) protein, an apoptosis inhibitory protein, in both cell lines was decreased more significant by paclitaxel in combination with seal oil than by paclitaxel alone. In addition, seal oil alone was found to induce apoptosis in both cell lines tested, which appeared to be due to the increased intracellular lipid peroxides produced. It is therefore concluded that paclitaxel in combination with seal oil demonstrated enhanced cytotoxicity and apoptosis in MCF-7 and MDA-MB-231 cells compared to paclitaxel alone, and the use of seal oil may be beneficial in the treatment of breast cancer.