Mental Illness Diagnoses May Not Cause All Mental Symptoms: A Simulation Study for Major Depressive Episodes, Dysthymic Disorder, and Manic Episodes.

Objectives This study aims to understand the statistical significance of the associations between diagnoses and symptoms based on simulations that have been used to understand the interpretability of mental illness diagnoses. Methods The symptoms for the diagnosis of major depressive episodes, dysthymic disorder, and manic episodes were extracted from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR, American Psychiatric Association, Philadelphia, Pennsylvania). Without real-world symptom data, we simulated populations using various combinations of symptom prevalence and correlations. Assuming symptoms occurred with similar prevalence and correlations, for each combination of symptom prevalence (0.05, 0.1, 0.3, 0.5, and 0.7) and correlation (0, 0.1, 0.4, 0.7, and 0.9), 100 cohorts with 10,000 individuals were randomly created. Diagnoses were made according to the DSM-IV-TR criteria. The associations between the diagnoses and their input symptoms were quantified with odds ratios and correlation coefficients. P-values from 100 cohorts for each combination of symptom prevalence and correlation were summarized. Results Three mental illness diagnoses were not significantly correlated with their own symptoms in all simulations, particularly when symptoms were not correlated, except for the symptom in the major criteria of major depressive episodes or dysthymic disorder. The symptoms for the diagnosis of major depressive episodes and dysthymic disorder were significantly correlated with these two diagnoses in some simulations, assuming 0.1, 0.4, 0.7, or 0.9 symptom correlations, except for one symptom. The overlap in the input symptoms for the diagnosis of major depressive episodes and dysthymic disorder also leads to significant correlations between these two diagnoses, assuming 0.1, 0.4, 0.7, and 0.9 correlations between input symptoms. Manic episodes are not significantly associated with the input symptoms of major depressive episodes and dysthymic disorder. Conclusion There are challenges to establish the causation between psychiatric symptoms and mental illness diagnoses. There is insufficient prevalence and incidence data to show all psychiatric symptoms exist or can be observed in patients. The diagnostic accuracy of symptoms to detect a disease cause is far from perfect. Assuming the symptoms of three mood disorders may present in patients, three diagnoses are not significantly associated with all psychiatric symptoms used to diagnose them. The diagnostic criteria of the three diagnoses have not been designed to guarantee significant associations between symptoms and diagnoses. Because statistical associations are important for making causal inferences, there may be a lack of causation between diagnoses and symptoms. Previous research has identified factors that lead to insignificant associations between diagnoses and symptoms, including biases due to data processing and a lack of epidemiological evidence to support the design of mental illness diagnostic criteria.

Peri-onset non-steroidal anti-inflammatory drugs use and organ failure in acute pancreatitis: A multicenter retrospective analysis.

BACKGROUND: Organ failure (OF) of acute pancreatitis (AP) significantly contributes to AP-related mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced complications of AP. AIMS: We aimed to investigate whether NSAIDs ameliorates SIRS and OF in patients with AP. METHODS: Eligible patients with AP were retrospectively identified in 4 hospitals between January 2015 and December 2018. Associations between peri-onset NSAIDs use (day -3 to day 3) and OF, persistent OF (POF), and SIRS within the first week were analyzed. Propensity score-matched (PSM) analysis and inverse probability of treatment-weighted (IPTW) analysis were used to estimate risk ratios. RESULTS: Among 1,528 patients with AP (97 [6.3%] with NSAIDs use), 242 (15.8%) developed organ failure, 89 (5.8%) progressed to POF, and 27 (1.8%) died within 3 months. PSM analysis showed no association between peri-onset NSAIDs and OF (risk ratio [RR], 1.00; 95% confidence interval [CI], 0.46 to 2.15) and POF (RR, 0.80; 95% CI, 0.21 to 2.98). IPTW analysis yielded similar results. Patients with and without peri-onset NSAIDs use were comparable with respect to OF, POF, and SIRS across subgroups defined by COX-2 selectivity and dose. CONCLUSION: Peri-onset NSAIDs use was not significantly associated with reduced OF.

The Upper Limits of Risk Ratios and Recommendations for Reporting Risk Ratios, Odds Ratios, and Rate Ratios.

Background Relative measures, including risk ratios (RRs) and odds ratios (ORs), are reported in many epidemiological studies. RRs represent how many times a condition is likely to develop when exposed to a risk factor. The upper limit of RRs is the multiplicative inverse of the baseline incidence. Ignoring the upper limits of RRs can lead to reporting exaggerated relative effect sizes. Objectives This study aims to demonstrate the importance of such upper limits for effect size reporting via equations, examples, and simulations and provide recommendations for the reporting of relative measures. Methods Equations to calculate RRs and their 95% confidence intervals (CIs) were listed. We performed simulations with 10,000 simulated subjects and three population variables: proportions at risk (0.05, 0.1, 0.3, 0.5, and 0.8), baseline incidence (0.05, 0.1, 0.3, 0.5, and 0.8), and RRs (0.5, 1.0, 5.0, 10.0, and 25.0). Subjects were randomly assigned with a risk based on the set of proportions-at-risk values. A disease occurred based on the baseline incidence among those not at risk. The incidence of those at risk was the product of the baseline incidence and the RRs. The 95% CIs of RRs were calculated according to Altman. Results The calculation of RR 95% CIs is not connected to the RR upper limits in equations. The RRs in the simulated populations at risk could reach the upper limits of RRs: multiplicative inverse of the baseline incidence. The upper limits to the derived RRs were around 1.25, 2, 3.3, 10, and 20, when the assumed baseline incidence rates were 0.8, 0.5, 0.3, 0.2, and 0.05, respectively. We demonstrated five scenarios in which the RR 95% CIs might exceed the upper limits. Conclusions Statistical significance does not imply the RR 95% CIs not exceeding the upper limits of RRs. When reporting RRs or ORs, the RR upper limits should be assessed. The rate ratio is also subject to a similar upper limit. In the literature, ORs tend to overestimate effect sizes. It is recommended to correct ORs that aim to approximate RRs assuming outcomes are rare. A reporting guide for relative measures, RRs, ORs, and rate ratios, is provided. Researchers are recommended to report whether the 95% CIs of relative measures, RRs, ORs, and rate ratios, overlap with the range of upper limits and discuss whether the relative measure estimates may exceed the upper limits.

Critical Hierarchical Appraisal and Reporting Tool for Composite Measures (CHAOS).

Background Composite measures are often used to represent certain concepts that cannot be measured with single variables and can be used as diagnoses, prognostic factors, or outcomes in clinical or health research. For example, frailty is a diagnosis confirmed based on the number of age-related symptoms and has been used to predict major health outcomes. However, undeclared assumptions and problems are prevalent among composite measures. Thus, we aim to propose a reporting guide and an appraisal tool for identifying these assumptions and problems. Methods We developed this reporting and assessment tool based on evidence and the consensus of experts pioneering research on index mining and syndrome mining. We designed a development framework for composite measures and then tested and revised it based on several composite measures commonly used in medical research, such as frailty, body mass index (BMI), mental illness diagnoses, and innovative indices mined for mortality prediction. We extracted review questions and reporting items from various issues identified by the development framework. This panel reviewed the identified issues, considered other aspects that might have been neglected in previous studies, and reached a consensus on the questions to be used by the reporting and assessment tool. Results We selected 19 questions in seven domains for reporting or critical assessment. Each domain contains review questions for authors and readers to critically evaluate the interpretability and validity of composite measures, which include candidate variable selection, variable inclusion and assumption declaration, data processing, weighting scheme, methods to aggregate information, composite measure interpretation and justification, and recommendations on the use. Conclusions For all seven domains, interpretability is central with respect to composite measures. Variable inclusion and assumptions are important clues to show the connection between composite measures and their theories. This tool can help researchers and readers understand the appropriateness of composite measures by exploring various issues. We recommend using this Critical Hierarchical Appraisal and repOrting tool for composite measureS (CHAOS) along with other critical appraisal tools to evaluate study design or risk of bias.

Frailty does not cause all frail symptoms: United States Health and Retirement Study.

BACKGROUND: Frailty is associated with major health outcomes. However, the relationships between frailty and frailty symptoms haven't been well studied. This study aims to show the associations between frailty and frailty symptoms. METHODS: The Health and Retirement Study (HRS) is an ongoing longitudinal biannual survey in the United States. Three of the most used frailty diagnoses, defined by the Functional Domains Model, the Burden Model, and the Biologic Syndrome Model, were reproduced according to previous studies. The associations between frailty statuses and input symptoms were assessed using odds ratios and correlation coefficients. RESULTS: The sample sizes, mean ages, and frailty prevalence matched those reported in previous studies. Frailty statuses were weakly correlated with each other (coefficients = 0.19 to 0.38, p < 0.001 for all). There were 49 input symptoms identified by these three models. Frailty statuses defined by the three models were not significantly correlated with one or two symptoms defined by the same models (p > 0.05 for all). One to six symptoms defined by the other two models were not significantly correlated with each of the three frailty statuses (p > 0.05 for all). Frailty statuses were significantly correlated with their own bias variables (p < 0.05 for all). CONCLUSION: Frailty diagnoses lack significant correlations with some of their own frailty symptoms and some of the frailty symptoms defined by the other two models. This finding raises questions like whether the frailty symptoms lacking significant correlations with frailty statuses could be included to diagnose frailty and whether frailty exists and causes frailty symptoms.

Diagnostic accuracy of symptoms for an underlying disease: a simulation study.

Symptoms have been used to diagnose conditions such as frailty and mental illnesses. However, the diagnostic accuracy of the numbers of symptoms has not been well studied. This study aims to use equations and simulations to demonstrate how the factors that determine symptom incidence influence symptoms' diagnostic accuracy for disease diagnosis. Assuming a disease causing symptoms and correlated with the other disease in 10,000 simulated subjects, 40 symptoms occurred based on 3 epidemiological measures: proportions diseased, baseline symptom incidence (among those not diseased), and risk ratios. Symptoms occurred with similar correlation coefficients. The sensitivities and specificities of single symptoms for disease diagnosis were exhibited as equations using the three epidemiological measures and approximated using linear regression in simulated populations. The areas under curves (AUCs) of the receiver operating characteristic (ROC) curves was the measure to determine the diagnostic accuracy of multiple symptoms, derived by using 2 to 40 symptoms for disease diagnosis. With respect to each AUC, the best set of sensitivity and specificity, whose difference with 1 in the absolute value was maximal, was chosen. The results showed sensitivities and specificities of single symptoms for disease diagnosis were fully explained with the three epidemiological measures in simulated subjects. The AUCs increased or decreased with more symptoms used for disease diagnosis, when the risk ratios were greater or less than 1, respectively. Based on the AUCs, with risk ratios were similar to 1, symptoms did not provide diagnostic values. When risk ratios were greater or less than 1, maximal or minimal AUCs usually could be reached with less than 30 symptoms. The maximal AUCs and their best sets of sensitivities and specificities could be well approximated with the three epidemiological and interaction terms, adjusted R-squared ≥ 0.69. However, the observed overall symptom correlations, overall symptom incidence, and numbers of symptoms explained a small fraction of the AUC variances, adjusted R-squared ≤ 0.03. In conclusion, the sensitivities and specificities of single symptoms for disease diagnosis can be explained fully by the at-risk incidence and the 1 minus baseline incidence, respectively. The epidemiological measures and baseline symptom correlations can explain large fractions of the variances of the maximal AUCs and the best sets of sensitivities and specificities. These findings are important for researchers who want to assess the diagnostic accuracy of composite diagnostic criteria.

Why Mental Illness Diagnoses Are Wrong: A Pilot Study on the Perspectives of the Public.

Background: Mental illness diagnostic criteria are made based on assumptions. This pilot study aims to assess the public's perspectives on mental illness diagnoses and these assumptions. Methods: An anonymous survey with 30 questions was made available online in 2021. Participants were recruited via social media, and no personal information was collected. Ten questions focused on participants' perceptions regarding mental illness diagnoses, and 20 questions related to the assumptions of mental illness diagnoses. The participants' perspectives on these assumptions held by professionals were assessed. Results: Among 14 survey participants, 4 correctly answered the relationships of 6 symptom pairs (28.57%). Two participants could not correctly conduct the calculations involved in mood disorder diagnoses (14.29%). Eleven (78.57%) correctly indicated that 2 or more sets of criteria were available for single diagnoses of mental illnesses. Only 1 (7.14%) correctly answered that the associations between symptoms and diagnoses were supported by including symptoms in the diagnostic criteria of the diagnoses. Nine (64.29%) correctly answered that the diagnosis variances were not fully explained by their symptoms. The confidence of participants in the major depressive disorder diagnosis and the willingness to take medications for this diagnosis were the same (mean = 5.50, standard deviation [SD] = 2.31). However, the confidence of participants in the symptom-based diagnosis of non-solid brain tumor was significantly lower (mean = 1.62, SD = 2.33, p < 0.001). Conclusion: Our study found that mental illness diagnoses are wrong from the perspectives of the public because our participants did not agree with all the assumptions professionals make about mental illness diagnoses. Only a minority of our participants obtained correct answers to the calculations involved in mental illness diagnoses. In the literature, neither patients nor the public have been engaged in formulating the diagnostic criteria of mental illnesses.

Interpretable Trials: Is Interpretability a Reason Why Clinical Trials Fail?

Background: There are clinical trials using composite measures, indices, or scales as proxy for independent variables or outcomes. Interpretability of derived measures may not be satisfying. Adopting indices of poor interpretability in clinical trials may lead to trial failure. This study aims to understand the impact of using indices of different interpretability in clinical trials. Methods: The interpretability of indices was categorized as: fair-to-poor, good, and unknown. In the literature, frailty indices were considered fair to poor interpretability. Body mass index (BMI) was highly interpretable. The other indices were of unknown interpretability. The trials were searched at clinicaltrials.gov on October 2, 2018. The use of indices as conditions/diseases or other terms was searched. The trials were grouped as completed, terminated, active, and other status. We tabulated the frequencies of frailty, BMI, and other indices. Results: There were 263,928 clinical trials found and 155,606 were completed or terminated. Among 2,115 trials adopting indices or composite measures as condition or disease, 244 adopted frailty and 487 used BMI without frailty indices. Significantly higher proportions of trials of unknown status used indices as conditions/diseases or other terms, compared to completed and terminated trials. The proportions of active trials using frailty indices were significantly higher than those of completed or terminated trials. Discussion: Clinical trial databases can be used to understand why trials may fail. Based on the findings, we suspect that using indices of poor interpretability may be associated with trial failure. Interpretability has not been conceived as an essential criterion for outcomes or proxy measures in trials. We will continue verifying the findings in other databases or data sources and apply this research method to improve clinical trial design. To prevent patients from experiencing trials likely to fail, we suggest further examining the interpretability of the indices in trials.

Simulation study to demonstrate biases created by diagnostic criteria of mental illnesses: major depressive episodes, dysthymia, and manic episodes.

OBJECTIVES: Composite diagnostic criteria alone are likely to create and introduce biases into diagnoses that subsequently have poor relationships with input symptoms. This study aims to understand the relationships between the diagnoses and the input symptoms, as well as the magnitudes of biases created by diagnostic criteria and introduced into the diagnoses of mental illnesses with large disease burdens (major depressive episodes, dysthymic disorder, and manic episodes). SETTINGS: General psychiatric care. PARTICIPANTS: Without real-world data available to the public, 100 000 subjects were simulated and the input symptoms were assigned based on the assumed prevalence rates (0.05, 0.1, 0.3, 0.5 and 0.7) and correlations between symptoms (0, 0.1, 0.4, 0.7 and 0.9). The input symptoms were extracted from the diagnostic criteria. The diagnostic criteria were transformed into mathematical equations to demonstrate the sources of biases and convert the input symptoms into diagnoses. PRIMARY AND SECONDARY OUTCOMES: The relationships between the input symptoms and diagnoses were interpreted using forward stepwise linear regressions. Biases due to data censoring or categorisation introduced into the intermediate variables, and the three diagnoses were measured. RESULTS: The prevalence rates of the diagnoses were lower than those of the input symptoms and proportional to the assumed prevalence rates and the correlations between the input symptoms. Certain input or bias variables consistently explained the diagnoses better than the others. Except for 0 correlations and 0.7 prevalence rates of the input symptoms for the diagnosis of dysthymic disorder, the input symptoms could not fully explain the diagnoses. CONCLUSIONS: There are biases created due to composite diagnostic criteria and introduced into the diagnoses. The design of the diagnostic criteria determines the prevalence of the diagnoses and the relationships between the input symptoms, the diagnoses, and the biases. The importance of the input symptoms has been distorted largely by the diagnostic criteria.

Opportunities and Challenges From Leading Trends in a Biomonitoring Project: Canadian Health Measures Survey 2007-2017.

Background: Biomonitoring can be conducted by assessing the levels of chemicals in human bodies and their surroundings, for example, as was done in the Canadian Health Measures Survey (CHMS). This study aims to report the leading increasing or decreasing biomarker trends and determine their significance. Methods: We implemented a trend analysis for all variables from CHMS biomonitoring data cycles 1-5 conducted between 2007 and 2017. The associations between time and obesity were determined with linear regressions using the CHMS cycles and body mass index (BMI) as predictors. Results: There were 997 unique biomarkers identified and 86 biomarkers with significant trends across cycles. Nine of the 10 leading biomarkers with the largest decreases were environmental chemicals. The levels of 1,2,3-trimethyl benzene, dodecane, palmitoleic acid, and o-xylene decreased by more than 60%. All of the 10 chemicals with the largest increases were environmental chemicals, and the levels of 1,2,4-trimethylbenzene, nonanal, and 4-methyl-2-pentanone increased by more than 200%. None of the 20 biomarkers with the largest increases or decreases between cycles were associated with BMI. Conclusions: The CHMS provides the opportunity for researchers to determine associations between biomarkers and time or BMI. However, the unknown causes of trends with large magnitudes of increase or decrease and their unclear impact on Canadians' health present challenges. We recommend that the CHMS plan future cycles on leading trends and measure chemicals with both human and environmental samples.

Using syndrome mining with the Health and Retirement Study to identify the deadliest and least deadly frailty syndromes.

Syndromes are defined with signs or symptoms that occur together and represent conditions. We use a data-driven approach to identify the deadliest and most death-averse frailty syndromes based on frailty symptoms. A list of 72 frailty symptoms was retrieved based on three frailty indices. We used data from the Health and Retirement Study (HRS), a longitudinal study following Americans aged 50 years and over. Principal component (PC)-based syndromes were derived based on a principal component analysis of the symptoms. Equal-weight 4-item syndromes were the sum of any four symptoms. Discrete-time survival analysis was conducted to compare the predictive power of derived syndromes on mortality. Deadly syndromes were those that significantly predicted mortality with positive regression coefficients and death-averse ones with negative coefficients. There were 2,797 of 5,041 PC-based and 964,774 of 971,635 equal-weight 4-item syndromes significantly associated with mortality. The input symptoms with the largest regression coefficients could be summed with three other input variables with small regression coefficients to constitute the leading deadliest and the most death-averse 4-item equal-weight syndromes. In addition to chance alone, input symptoms' variances and the regression coefficients or p values regarding mortality prediction are associated with the identification of significant syndromes.

Composite diagnostic criteria are problematic for linking potentially distinct populations: the case of frailty.

Composite diagnostic criteria are common in frailty research. We worry distinct populations may be linked to each other due to complicated criteria. We aim to investigate whether distinct populations might be considered similar based on frailty diagnostic criteria. The Functional Domains Model for frailty diagnosis included four domains: physical, nutritive, cognitive and sensory functioning. Health and Retirement Study participants with two or more deficiencies in the domains were diagnosed frail. The survival distributions were analyzed using discrete-time survival analysis. The distributions of the demographic characteristics and survival across the groups diagnosed with frailty were significantly different (p < 0.05). A deficiency in cognitive functioning was associated with the worst survival pattern compared with a deficiency in the other domains (adjusted p < 0.05). The associations of the domains with mortality were cumulative without interactions. Cognitive functioning had the largest effect size for mortality prediction (Odds ratios, OR = 2.37), larger than that of frailty status (OR = 1.92). The frailty diagnostic criteria may take distinct populations as equal and potentially assign irrelevant interventions to individuals without corresponding conditions. We think it necessary to review the adequacy of composite diagnostic criteria in frailty diagnosis.

Taiwanese consensus recommendations for acute pancreatitis.

The incidence of acute pancreatitis and related health care utilization are increasing. Acute pancreatitis may result in organ failure and various local complications with risks of morbidity and even mortality. Recent advances in research have provided novel insights into the assessment and management for acute pancreatitis. This consensus is developed by Taiwan Pancreas Society to provide an updated, evidence-based framework for managing acute pancreatitis.

Urinary trypsinogen-2 level and local complications of acute pancreatitis.

BACKGROUND AND AIM: Local complications of acute pancreatitis (AP) carry risks of morbidity/mortality. This study aimed to assess whether urinary trypsinogen-2 levels and Bedside Index for Severity in Acute Pancreatitis (BISAP) score on admission predicted subsequent local complications. METHODS: One hundred and forty-four consecutive patients with AP were prospectively followed till 6 months after discharge. Urinary trypsinogen-2 levels were measured within 24 h of admission. Local complications (acute peripancreatic fluid collection, acute necrotic collection, pseudocyst, and walled-off necrosis) were diagnosed by abdominal computed tomography. Cut-off for trypsinogen-2 level was assessed using receiver operating characteristic curve, and predictors of local complications were analyzed by logistic regression. RESULTS: Thirty-seven (25.7%) patients developed local complications. Urinary trypsinogen-2 levels were significantly higher in patients with local complications compared with those without local complications (median [interquartile range], 3210 [620-9764.4] µg/L vs 627.3 [72.3-5895] µg/L, P = 0.006). Urinary trypsinogen-2 significantly outperformed BISAP score in predicting local complications (area under the receiver operating characteristic curve 0.65 [95% CI: 0.55-0.75] vs 0.48 [95% CI: 0.38-0.58], P = 0.005). At the optimal cut-off of 500 µg/L, the sensitivity, specificity, positive predictive value, and negative predictive value of trypsinogen-2 level were 78.4%, 45.8%, 33.3%, and 86.0%, respectively. Urinary trypsinogen-2 level > 500 µg/L was an independent predictor of local complications (adjusted odds ratio, 3.72; 95% CI: 1.42-9.76; P = 0.007). By contrast, BISAP score ≥ 3 and pleural effusion predicted organ failure but not local complications. CONCLUSION: In a prospective cohort, urinary trypsinogen-2 level > 500 µg/L independently predicted local complications of AP.

Drug trends among non-institutionalized Canadians and the impact of data collection changes in the Canadian Health Measures Survey 2007 to 2015.

BACKGROUND: There is a global trend of increasing use in prescription and over-the-counter (OTC) drugs. This hasn't been verified in Canada. In addition, there are changes made to the collection method of medication information after the Canadian Health Measures Survey (CHMS) cycle 2. This study aims to review the potential impact of the changes in medication data collection and the trends in medication use if data quality remains similar throughout the CHMS cycles 1 to 4. This is fundamental for the analysis of this biomonitoring database. METHODS: The CHMS cycle 1 to 4 medication and household data were used to study the trends of medication use between 2007 and 2015. The use of prescription or OTC drugs was grouped based on the first levels of the Anatomical Therapeutic Chemical (ATC) Classification system. The total numbers of medications were asked in all cycles. However, only a maximum of 15 and 5 drugs could be respectively reported for existing and new prescription or OTC drugs in cycles 1 and 2. There were no restrictions on drug reporting after cycle 2. The trends of medication use were described as ratios, compared to cycle 1. RESULTS: The total numbers of the types of medication ever identified decreased from 739 to 603 between cycles 1 and 4. The proportions of using any drugs were from 0.90 to 0.88 between cycles 1 and 4 (ratio = 1.08 in cycle 4, 95% CI = 0.89 to 1.26). The numbers of drugs in use were from 3.9 to 3.8 (ratio = 1.05 in cycle 4, 95% CI = 0.86 to 1.24). The proportions of prescription drug use were from 0.53 to 0.55 (ratio = 1.13 in cycle 4, 95% CI = 0.89 to 1.37), while the numbers of prescription were from 1.51 to 1.68 (ratio = 1.20 in cycle 4, 95% CI = 0.92 to 1.48). The use of diabetes and thyroid medication had trends similar to the respective disease prevalence. The use and the numbers of drugs for blood and blood forming organs significantly increased between cycles 1 and 4 (ratio = 1.56 in cycle 4, 95% CI = 1.03 to 2.10). CONCLUSIONS: There is an increasing trend in the use of blood and blood forming agents through cycles 2 to 4 and cardiovascular drugs in cycle 3. For diabetes and thyroid medication, the proportions of medication use increase proportionally with disease prevalence. The changes in the medication information collection method may not have important impact on the reporting of the use of prescription or OTC drugs.

A proposal for a self-rated frailty index and status for patient-oriented research.

OBJECTIVE: Frailty indices are important predictors of major health outcomes, but mostly designed by and for researchers and specialists. Three of the most commonly used theory-based indices are composite measures that are subject to arbitrary assumptions and biases introduced due to data processing. A complicated index can be simplified with fewer items. The theory-based frailty indices are not optimal and neglect patients' perspectives. This study aims to compare different definitions of frailty and propose a self-rated measure of frailty index and status. RESULTS: Frailty was defined differently by laypeople and researchers/clinicians. Patients' and laypeople's perspectives seemed neglected. Existing frailty indices had shortcomings related to the use of composite measures, assumptions of frailty theories, and the lack of novel information. To avoid these shortcomings, we suggested asking individuals "on a scale of 0 to 10, how frail do you think you are?" and "by answering yes or no, do you consider yourself to be frail?" to determine frailty on continuous and dichotomous scales respectively. However, there will be other issues emerging with these new measures, such as the need for feasibility and validity studies, as well as acceptability by researchers.

Trend analysis for national surveys: Application to all variables from the Canadian Health Measures Survey cycle 1 to 4.

BACKGROUND: Trend analysis summarizes patterns over time in the data to show the direction of change and can be used to investigate uncertainties in different time points and associations with other factors. However, this approach is not widely applied to national surveys and only selected outcomes are investigated. This study demonstrates a research framework to conduct trend analysis for all variables in a national survey, the Canadian Health Measures Survey (CHMS). DATA AND METHODS: The CHMS cycle 1 to 4 was implemented between 2007 and 2015. The characteristics of all variables were screened and associated to the weight variables. Missing values were identified and cleaned according to the User Guide. The characteristics of all variables were extracted and used to guide data cleaning. Trend analysis examined the statistical significance of candidate predictors: the cycles, age, sex, education, household income and body mass index (BMI). R (v3.2) and RStudio (v0.98.113) were used to develop the framework. RESULTS: There were 26557 variables in 79 data files from four cycles. There were 1055 variables significantly associated with the CHMS cycles and 2154 associated with the BMI after controlling for other predictors. The trend of blood pressure was similar to those published. CONCLUSION: Trend analysis for all variables in the CHMS is feasible and is a systematic approach to understand the data. Because of trend analysis, we have detected data errors and identified several environmental biomarkers with extreme rates of change across cycles. The impact of these biomarkers has not been well studied by Statistics Canada or others. This framework can be extended to other surveys, especially the Canadian Community Health Survey.

A network perspective of engaging patients in specialist and chronic illness care: The 2014 International Health Policy Survey.

BACKGROUND: Patient engagement helps to improve health outcomes and health care quality. However, the overall relationships among patient engagement measures and health outcomes remain unclear. This study aims to integrate expert knowledge and survey data for the identification of measures that have extensive associations with other variables and can be prioritized to engage patients. METHODS: We used the 2014 International Health Policy Survey (IHPS), which provided information on elder adults in 11 countries with details in patient characteristics, healthcare experiences, and patient-physician communication. Patient engagement or support was measured with eight variables including patients' treatment choices, involvement, and treatment priority setting. Three types of care were identified: primary, specialist and chronic illness care. Specialists were doctors specializing in one area of health care. Chronic illness included eight chronic conditions surveyed. Expert knowledge was used to assist variable selection. We used Bayesian network models consisting of nodes that represented variables of interest and arcs that represented their relationships. RESULTS: Among 25,530 participants, the mean age was 68.51 years and 57.40% were females. The distributions of age, sex, education, and patient engagement were significantly different across countries. For chronic illness care, written plans provided by professionals were linked to treatment feasibility and helpfulness. Whether professionals contacted patients was associated with the availability of professionals they could reach for chronic illness care. For specialist care, if specialists provided treatment choices, patients were more likely to be involved and discuss about what mattered to them. CONCLUSION: The strategies to engage patients may depend on the types of care, specialist or chronic illness care. For the study on the observational IHPS data, network modeling is useful to integrate expert knowledge. We suggest considering other theory-based patient engagement in major surveys, as well as engaging patients in their healthcare by providing written plans and actively communicating with patients for chronic illnesses, and encouraging specialists to discuss and provide treatment options.

Index or illusion: The case of frailty indices in the Health and Retirement Study.

INTRODUCTION: Frailty is a geriatric syndrome that has been defined differently with various indices. Without a uniform definition, it remains unclear how to interpret and compare different frailty indices (FIs). With the advances in index mining, we find it necessary to review the implicit assumptions about the creation of FIs. We are concerned the processing of frailty data may introduce measurement error and bias. We aim to review the assumptions, interpretability and predictive power of FIs regarding mortality. METHODS: Three FIs, the Functional Domains Model proposed by Strawbridge et al. (1998), the Burden Model by Rockwood et al. (2007) and the Biologic Syndrome Model by Fried et al. (2004), were directly compared using the data from the Health and Retirement Study (HRS), a longitudinal study since 1996 mainly following up Americans aged 50 years and over. The FIs were reproduced according to Cigolle et al. (2009) and interpreted with their input variables through forward-stepwise regression. Biases were the residuals of the FIs that could not be explained by own input variables. Any four of the input variables were used to create alternative indices. Discrete-time survival analysis was conducted to compare the predictive power of FIs, input variables and alternative indices on mortality. RESULTS: We found frailty a syndrome not unique to the elderly. The FIs were produced with different degrees of bias. The FIs could not be fully interpreted with the theory-based input variables. The bias induced by the Biological Syndrome Model better predicted mortality than frailty status. A complicated FI, the Burden Model, could be simplified. The input variables better predicted mortality than the FIs. The continuous FIs predicted mortality better than the frailty statuses. At least 6865 alternative indices better predicted mortality than the FIs. CONCLUSION: FIs have been used as outcome in clinical trials and need to be reviewed for adequacy based on our findings. The three FIs are not closely linked to the theories because of bias introduced by data manipulation and excessive numbers of input variables. We are developing new algorithms to develop and validate innovative indices.

Stages of Biological Development across Age: An Analysis of Canadian Health Measure Survey 2007-2011.

INTRODUCTION: The stages of biological development are not clearly defined despite the fact that they have been used to refer to concepts such as adolescence and aging. This study aimed to (1) propose and test a framework to search for stages of representative components and determine stages of stability and transition, (2) identify stages of biological development based on health questionnaire and biomarker data, and (3) interpret the major trajectories in a health and biomarker database. METHODS: This study analyzed the data on the Canadian Health Measures Survey (CHMS) interviewees from cycle 1 to 3 (2007-2013) in Canada. We selected 282 variables containing information from questionnaire and on biomarkers after removing redundant variables based on high correlation. Fifty-nine nominal variables were replaced by 122 binominal variables, leaving 345 variables for analysis. Principal component (PC) analysis was conducted to summarize the data and the loadings were used to interpret the PCs. A stable stage was assumed to be the age groups without significantly different values of PCs. RESULTS: The CHMS interviewed 16,340 Canadians. Of all, 51.25% were female. The age ranged from 6 to 79 years (mean = 34.41 years, 95% CI = 34.74-34.08). The proportions of total variance explained by the first three PCs were 12.14, 4.03, and 3.19%, respectively. The differences of the first PC were not significant, especially between age 22 and 33, 34 and 40, 41 and 45, 46 and 71, and 72 and 79 years (adjusted p > 0.05 for all). The leading variable, in terms of the variance contributed to PC1, was time spent in physical activities, followed by variables related to alcohol consumption, and smoking. The 13 leading contributors to PC2 variances were all lung function measures. DISCUSSION AND CONCLUSION: There are stages of stability and transition across all age groups based on the first PCs. The first and second PCs are related to physical development and lung function. The identification of stable stages is the first step to understanding how human biology develops in a population perspective and will be important for research that relies on a research population with similar characteristics to draw samples for observation or intervention.