OBJECTIVE: Advance directives (AD) are based on state-specific statutes that vary in structure, terminology, and options. This variability leads to inconsistent end-of-life (EOL) care for patients who have executed an AD in one state but fall ill in another state. This study revisits a 2002 article that identified considerable differences in ADs to determine whether ADs have become more uniform.
METHODS: ADs from all 50 states and the District of Columbia were examined to determine the frequency of document types and seven key issues. The results were = compared to the 2002 study using non-parametric approaches. Mean numbers of key issues were compared using t-tests and one-way ANOVA.
RESULTS: Consistent with 2002, three states in 2023 provide statutes for Health Care Power of Attorney (HCPOA). However, states offering a combined HCPOA, and living will (LW), deemed an advance directive for health care (ADHC), increased from 13 to 30. Between both studies, Long Term Care increased significantly in LW and ADHC, while Artificial Sustenance significantly increased in LW. Despite the rising prevalence of Alzheimer\'s in the United States, only 10% of states included this issue in 2023.
CONCLUSIONS: Despite evolving healthcare trends, minimal revisions have been made to ADs since 2002. This lack of uniformity can cause confusion regarding proper understanding of EOL wishes. The authors recommend that the Uniform Act for Advance Directives be revisited to promote greater uniformity in ADs and ensure that individuals\' preferences are understood and respected across different states.

A biomarker is a measurable indicator of the severity or presence of a disease or medical condition in biomedical or epidemiological research. Biomarkers may help in early diagnosis and prevention of diseases. Several biomarkers have been identified for many diseases such as carbohydrate antigen 19-9 for pancreatic cancer. However, biomarkers may be measured with errors due to many reasons such as specimen collection or day-to-day within-subject variability of the biomarker, among others. Measurement error in the biomarker leads to bias in the regression parameter estimation for the association of the biomarker with disease in epidemiological studies. In addition, measurement error in the biomarkers may affect standard diagnostic measures to evaluate the performance of biomarkers such as the receiver operating characteristic (ROC) curve, area under the ROC curve, sensitivity, and specificity. Measurement error may also have an effect on how to combine multiple cancer biomarkers as a composite predictor for disease diagnosis. In follow-up studies, biomarkers are often collected intermittently at examination times, which may be sparse and typically biomarkers are not observed at the event times. Joint modeling of longitudinal and time-to-event data is a valid approach to account for measurement error in the analysis of repeatedly measured biomarkers and time-to-event outcomes. In this article, we provide a literature review on existing methods to correct for estimation in regression analysis, diagnostic measures, and joint modeling of longitudinal biomarkers and survival outcomes when the biomarkers are measured with errors. This article is categorized under: Statistical and Graphical Methods of Data Analysis > Robust MethodsStatistical and Graphical Methods of Data Analysis > EM AlgorithmStatistical Models > Survival Models.

Community-based palliative care (CBPC) clinicians sometimes contend with an ethically charged scenario when they encounter patients for the first time: The patient\'s spouse, or other loved one or caregiver, revokes the patient\'s valid informed consent to initiate care. While surrogates are usually motivated by protective instincts, there are other situations where surrogates act out of self-interest. This article considers whether it is ever ethically justified for an adult to revoke another adult\'s valid informed consent to initiate palliative care services. The article examines this scenario from three perspectives: the patient\'s capacity to give or relinquish informed consent, the surrogate\'s intent and use of substituted judgment or best interest, and the clinician\'s duty to provide clinical care. This ethical analysis argues that CBPC clinicians have an ethical responsibility to provide palliative care services for patients who have given valid informed consent for those services even when a surrogate acts as an interfering or oppositional force.

Aside from human bones, epoxy-based synthetic bones are regarded as the gold standard for biomechanical testing os osteosyntheses. There is a significant discrepancy in biomechanical testing between the determination of fracture stability due to implant treatment in experimental methods and their ability to predict the outcome of stability and fracture healing in a patient. One possible explanation for this disparity is the absence of population-specific variables such as age, gender, and ethnicity in artificial bone, which may influence the geometry and mechanical properties of bone. The goal of this review was to determine whether commercially available artificial bones adequately represent human anatomical variability for mechanical testing of femoral osteosyntheses. To summarize, the availability of suitable bone surrogates currently limits the validity of mechanical evaluations of implant-bone constructs. The currently available synthetic bones neither accurately reflect the local mechanical properties of human bone, nor adequately represent the necessary variability between various populations, limiting their generalized clinical relevance.

UNASSIGNED: Bleeding events are frequently applied as safety end points for randomized controlled trials (RCTs) investigating the effect of antithrombotic agents in patients with coronary artery disease. However, whether a bleeding event is a valid surrogate for death remain uncertain.
UNASSIGNED: This study aimed to assess the correlation between the treatment effect on bleeding events and mortality.
UNASSIGNED: Multiple databases were searched to identify RCTs studying antithrombotic agents for patients with coronary artery disease through August 2022. Major and minor bleeding events were defined in included trials, mostly defined with BARC (Bleeding Academic Research Consortium) or TIMI (Thrombolysis In Myocardial Infarction) criteria. Trial-level correlations between nonfatal bleeding events and mortality were assessed. We performed subgroup analyses by the definitions of bleeding (BARC vs TIMI criteria), study year, and follow-up duration. We used a cutoff with a lower limit of 95% confidence interval of R2 >0.72 as a strong correlation and with an upper limit of 95% confidence interval of R2 <0.50 as a weak correlation.
UNASSIGNED: A total of 48 RCTs with 181,951 participants were analyzed. Overall, trial-level R2 for major and minor bleeding were 0.09 (95% CI: 0.00-0.26) and 0.09 (95% CI: 0.00-0.27) for all-cause or cardiovascular death, respectively. When confined to major bleeding, R2 were 0.03 (95% CI: 0.00-0.13) and 0.01 (95% CI: 0.00-0.05), respectively. All of the subgroup analyses did not show any significant correlations.
UNASSIGNED: We demonstrated a trial-defined bleeding event may not be a valid surrogate for mortality in RCTs investigating the effect of antithrombotic agents for coronary artery disease.

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Bone stress injuries are prevalent among athletes and military recruits and can significantly compromise training schedules. The development of an ankle-foot orthosis to reduce tibial load and enable a faster return to activity will require new device testing methodologies capable of capturing the contribution of muscular force on tibial strain. Thus, an actuated robotic surrogate leg was developed to explore how tibial strain changes with different ankle-foot orthosis conditions. The purpose of this work was to assess the reliability, scalability, and behavior of the surrogate. A dual actuation system consisting of a Bowden cable and a vertical load applied to the femur via a material testing system, replicated the action-reaction of the Achilles-soleus complex. Maximum and minimum principal strain, maximum shear strain, and axial strain were measured by instrumented strain gauges at five locations on the tibia. Strains were highly repeatable across tests but did not consistently match in vivo data when scaled. However, the stiffness of the ankle-foot orthosis strut did not systematically affect tibial load, which is consistent with in vivo findings. Future work will involve improving the scalability of the results to match in vivo data and using the surrogate to inform exoskeletal designs for bone stress injuries.

Epidemiological studies often encounter a challenge due to exposure measurement error when estimating an exposure-disease association. A surrogate variable may be available for the true unobserved exposure variable. However, zero-inflated data are encountered frequently in the surrogate variables. For example, many nutrient or physical activity measures may have a zero value (or a low detectable value) among a group of individuals. In this paper, we investigate regression analysis when the observed surrogates may have zero values among some individuals of the whole study cohort. A naive regression calibration without taking into account a probability mass of the surrogate variable at 0 (or a low detectable value) will be biased. We developed a regression calibration estimator which typically can have smaller biases than the naive regression calibration estimator. We propose an expected estimating equation estimator which is consistent under the zero-inflated surrogate regression model. Extensive simulations show that the proposed estimator performs well in terms of bias correction. These methods are applied to a physical activity intervention study.

Objectives Renal replacement therapy (RRT) is increasingly adopted for critically ill patients diagnosed with acute kidney injury, but the optimal time for initiation remains unclear and prognosis is uncertain, leading to medical complexity, ethical conflicts, and decision dilemmas in intensive care unit (ICU) settings. This study aimed to develop a decision aid (DA) for the family surrogate of critically ill patients to support their engagement in shared decision-making process with clinicians. Methods Development of DA employed a systematic process with user-centered design (UCD) principle, which included: (i) competitive analysis: searched, screened, and assessed the existing DAs to gather insights for design strategies, developmental techniques, and functionalities; (ii) user needs assessment: interviewed family surrogates in our hospital to explore target user group\'s decision-making experience and identify their unmet needs; (iii) evidence syntheses: integrate latest clinical evidence and pertinent information to inform the content development of DA. Results The competitive analysis included 16 relevant DAs, from which we derived valuable insights using existing resources. User decision needs were explored among a cohort of 15 family surrogates, revealing four thematic issues in decision-making, including stuck into dilemmas, sense of uncertainty, limited capacity, and delayed decision confirmation. A total of 27 articles were included for evidence syntheses. Relevant decision-making knowledge on disease and treatment, as delineated in the literature sourced from decision support system or clinical guidelines, were formatted as the foundational knowledge base. Twenty-one items of evidence were extracted and integrated into the content panels of benefits and risks of RRT, possible outcomes, and reasons to choose. The DA was drafted into a web-based phototype using the elements of UCD. This platform could guide users in their preparation of decision-making through a sequential four-step process: identifying treatment options, weighing the benefits and risks, clarifying personal preferences and values, and formulating a schedule for formal shared decision-making with clinicians. Conclusions We developed a rapid prototype of DA tailored for family surrogate decision makers of critically ill patients in need of RRT in ICU setting. Future studies are needed to evaluate its usability, feasibility, and clinical effects of this intervention.

Canine distemper virus (CDV) is a highly contagious pathogen within the morbillivirus genus infecting a wide range of different carnivore species. The virus shares most biological features with other closely related morbilliviruses, including clinical signs, tissue tropism, and replication cycle in the respective host organisms.In the laboratory environment, experimental infections of ferrets with CDV were established as a potent surrogate model for the analysis of several aspects of the biology of the human morbillivirus, measles virus (MeV). The animals are naturally susceptible to CDV and display severe clinical signs resembling the disease seen in patients infected with MeV. As seen with MeV, CDV infects immune cells and is thus associated with a strong transient immunosuppression. Here we describe several methods to evaluate viral load and parameters of immunosuppression in blood-circulating immune cells isolated from CDV-infected animals.