Long-term trajectories of ambulatory impairment in multiple sclerosis.

BACKGROUND: Ambulatory impairment is a common and complex manifestation of multiple sclerosis (MS), and longitudinal patterns are not well understood. OBJECTIVE: To characterize longitudinal walking speed trajectories in a general MS patient population and in those with early disease (⩽ 5 years from onset), identify subgroups with similar patterns, and examine associations with individual attributes. METHODS: Using a retrospective cohort study design, latent class growth analysis was applied to longitudinal timed 25-foot walk (T25-FW) data from 7683 MS patients, to determine T25-FW trajectories. Associations were evaluated between trajectory assignment and individual attributes. Analyses were repeated for 2591 patients with early disease. RESULTS: In the general patient population, six trajectories were discerned, ranging from very minimal to very high impairment at baseline, with variability in impairment accrual. The clusters with moderate to very high walking impairment were associated with being female, older and Black American, longer symptom duration, progressive course, and depressive symptoms. In the early disease subset, eight trajectories were discerned that included two subgroups that rapidly accrued impairment. CONCLUSION: We identified novel subgroups of MS patients will distinct long-term T25-FW trajectories. These results underscore that socially disadvantaged and economically marginalized MS patients are the most vulnerable for severe ambulatory impairment.

Decentralised clinical trials in multiple sclerosis research.

Randomised controlled trials (RCTs) play an important role in multiple sclerosis (MS) research, ensuring that new interventions are safe and efficacious before their introduction into clinical practice. Trials have been evolving to improve the robustness of their designs and the efficiency of their conduct. Advances in digital and mobile technologies in recent years have facilitated this process and the first RCTs with decentralised elements became possible. Decentralised clinical trials (DCTs) are conducted remotely, enabling participation of a more heterogeneous population who can participate in research activities from different locations and at their convenience. DCTs also rely on digital and mobile technologies which allows for more flexible and frequent assessments. While hospitals quickly adapted to e-health and telehealth assessments during the COVID-19 pandemic, the conduct of conventional RCTs was profoundly disrupted. In this paper, we review the existing evidence and gaps in knowledge in the design and conduct of DCTs in MS.

Characterizing fatigue phenotypes with other symptoms and clinically relevant outcomes among people with multiple sclerosis.

PURPOSE: Fatigue is a common symptom of multiple sclerosis (MS) and can adversely affect all aspect of quality of life. The etiology of fatigue remains unclear, and its treatments are suboptimal. Characterizing the phenotypes of fatigued persons with MS may help advance research on fatigue's etiology and identify ways to personalize fatigue interventions to improve quality of life. The purpose of this study was to identify fatigue phenotypes; examine phenotype stability overtime; and characterize phenotypes by health and function, social and environmental determinants, psychosocial factors, and engagement in healthy behaviors. METHODS: We conducted a longitudinal study over a 3-month period with 289 fatigued participants with MS. To identify fatigue phenotypes and determine transition probabilities, we used latent profile and transition analyses with valid self-report measures of mental and physical fatigue severity, the mental and physical impact of fatigue, depression, anxiety, and sleep quality. We used ANOVAs and effect sizes to characterize differences among phenotypes. RESULTS: The best fitting model included six subgroups of participants: Mild Phenotype, Mild-to-Moderate Phenotype, Moderate-to-Severe Phenotype, Severe Phenotype, Fatigue-dominant Phenotype, and Mental Health-dominant Phenotype. The transition analysis indicated that phenotypic membership was highly stable. Variables with a large eta squared effect size included environmental barriers, self-efficacy, and fatigue catastrophizing. CONCLUSION: These results indicate that the magnitude of fatigue experienced may be more important to consider than the type of fatigue when characterizing fatigue phenotypes. Future research should explore whether tailoring interventions to environmental barriers, self-efficacy, and fatigue catastrophizing reduce the likelihood of transitioning to a more severe phenotype.

Food Insecurity Trajectories in the US During the First Year of the COVID-19 Pandemic.

INTRODUCTION: The objective of this study was to characterize population-level trajectories in the probability of food insecurity in the US during the first year of the COVID-19 pandemic and to examine sociodemographic correlates associated with identified trajectories. METHODS: We analyzed data from the Understanding America Study survey, a nationally representative panel (N = 7,944) that assessed food insecurity every 2 weeks from April 1, 2020, through March 16, 2021. We used latent class growth analysis to determine patterns (or classes) of pandemic-related food insecurity during a 1-year period. RESULTS: We found 10 classes of trajectories of food insecurity, including 1 class of consistent food security (64.7%), 1 class of consistent food insecurity (3.4%), 5 classes of decreasing food insecurity (15.8%), 2 classes of increasing food insecurity (4.6%), and 1 class of stable but elevated food insecurity (11.6%). Relative to the class that remained food secure, other classes were younger, had a greater proportion of women, and tended to identify with a racial or ethnic minority group. CONCLUSION: We found heterogeneous longitudinal patterns in the development, resolution, or persistence of food insecurity during the first year of the COVID-19 pandemic. Experiences of food insecurity were highly variable across the US population, with one-third experiencing some form of food insecurity risk. Findings have implications for identifying population groups who are at increased risk of food insecurity and related health disparities beyond the first year of the pandemic.

SARS-CoV-2 Infection among Serially Tested Emergency Medical Services Workers.

BACKGROUND: Emerging research has examined the prevalence of severe acute respiratory syndrome virus 2 (SARS-CoV-2) infections in numerous settings, but a critical gap in knowledge is an understanding of the rate of infection among first responders. METHODS: We conducted a prospective serial serologic survey by recruiting public first responders from Cleveland area emergency medical services agencies and fire departments. Volunteers submitted a nasopharyngeal swab for SARS-CoV-2 PCR testing and serum samples to detect the presence of antibodies to SARS-CoV-2 on two visits scheduled approximately 3 weeks apart. RESULTS: 296 respondents completed a first visit and 260 completed the second. While 71% of respondents reported exposure to SARS-CoV-2, only 5.4% (95% CI 3.1-8.6) had positive serologic testing. No subjects had a positive PCR. On the first visit, eight (50%) of the test-positive subjects had no symptoms and only one (6.2%) sought healthcare or missed school or work. None of the subjects that tested negative on the first visit were positive on their second. CONCLUSIONS: While our results show a relatively low rate of test positivity for SARS-CoV-2 amongst first responders, most were either asymptomatic or mildly symptomatic. The potential risk of asymptomatic transmission both between first responders and from first responders to vulnerable patients requires more study.

Higher dose weekly fluoxetine in hemodialysis patients: A case series report.

OBJECTIVE: The antidepressant medication fluoxetine at 90 mg dosed weekly is as effective and safe as standard formulation fluoxetine 20 mg dosed daily in patients with major depressive disorder. Weekly fluoxetine has not been well studied in hemodialysis patients, and doses beyond 90 mg/week have not been described in this population. This case series, derived from a larger study on depression in hemodialysis patients, describes the use of weekly fluoxetine at dosages beyond 90 mg/week. METHOD: Hemodialysis patients with depressive symptom severity scored ≥10 on the 9-item Patient Health Questionnaire and major depressive disorder confirmed with Mini International Neuropsychiatric Interview were initially prescribed daily fluoxetine for two weeks and then transitioned to weekly fluoxetine. Dosage titration was made at the discretion of the prescribing clinician. Fluoxetine was continued for a total of 12 weeks. RESULTS: Four women, aged 24 to 65 years, on hemodialysis for 1 to 18 years, were started on weekly fluoxetine that was increased over several weeks up to 180 mg. Side effects included restlessness, dry mouth, sedation, and lightheadedness. Two patients ultimately had their weekly fluoxetine decreased back to 90 mg. However, all four continued weekly fluoxetine as part of poststudy aftercare and no longer met diagnostic criteria for major depressive disorder, current episode. CONCLUSIONS: Weekly fluoxetine at doses of 180 mg may be a reasonable treatment consideration for hemodialysis patients who have partial or insufficient antidepressant response. Side effects may limit tolerance of the 180 mg dose in some individuals. Future research should investigate longer term health outcomes of weekly fluoxetine in this population.

Changes in Self-Reported Depressive Symptoms Among Adults in the United States From 2005 to 2016.

BACKGROUND: This study examined interview data from the National Health and Nutrition Examination Survey from 2005 to 2016. AIM: To determine national trends in self-reported depressive symptoms. METHOD: Depressive symptoms were assessed using self-reported data on the nine-item Patient Health Questionnaire (PHQ-9), with a total score ≥10 and an individual item score of 2 or 3, indicating greater severity. RESULTS: A total of 31,191 individuals contributed PHQ-9 data from 2005 to 2016. The absolute proportion of individuals with total PHQ-9 score ≥10 increased from 6.2% to 8.1%. After adjustment for participant demographic characteristics and comorbid conditions, the odds ratio for high PHQ-9 score at the end versus the beginning of the study interval was 1.27 (95% confidence interval [CI: 1.07, 1.50]). Anhedonia, guilt/worthlessness, appetite, and hypoactivity/hyperactivity had the largest increases in individual item risk after adjusting for demographic and comorbid characteristics. CONCLUSIONS: There were sizeable increases in the prevalence of self-reported depressive symptoms in the United States over an 11-year period. Further work is needed to understand the reasons for and implications of this increase. However, the results suggest greater efforts should be made by health care providers to screen for depressive symptoms that may warrant further assessment, treatment, or referral to mental health services as needed.

Depressive Symptom Trajectories Among People Living with HIV in a Collaborative Care Program.

Depressive symptoms may differ in severity and change over time in people living with HIV (PLWH). Describing depression trajectories and associated clinical characteristics of PLWH in an interventional study may help in developing a more personalized medicine approach. Using latent class growth analysis four, 15-month self-reported depression trajectories were identified in 416 PLWH participating in a collaborative care program. The four subgroups were characterized by improving (58.4% [of participants]), worsening (9.4%), highly responsive (19.5%) and persistently severe (12.7%) depressive symptoms. A high proportion of individuals were in trajectories marked by improvement. Further, the highly responsive group had on average, over 50% reduction of self-reported depressive symptoms. Self-reported trauma, posttraumatic stress disorder, lower neighborhood-level education and fewer HIV and psychiatry clinic visits were associated with worsening or persistently severe depressive symptom trajectories. Members of the persistently severe group were less likely to be virally suppressed after 12-months. Identifying subgroups of PLWH based on changes in self-reported depressive symptoms may further inform intervention approaches that can advance care.

Erythrocytosis is associated with intradialytic hypotension: a case series.

BACKGROUND: For patients with end stage renal disease undergoing hemodialysis, erythrocytosis occurs rarely. Erythrocytosis increases the risk of thrombosis, which is a common complication in hemodialysis patients. The risk of thrombosis may also be increased by hypotension. The purpose of our report is to examine the relationship between intradialytic hypotension and erythrocytosis. CASE PRESENTATION: We present a series of five patients with end stage renal disease and erythrocytosis (peak hemoglobin range 15.2-18.5 g/dL). All were erythropoiesis-stimulating agent naïve and non-smokers. Prior to developing erythrocytosis, each patient developed recurring episodes of intradialytic hypotension over several months. A statistically significant inverse correlation was observed between nadir intradialytic systolic blood pressure and hemoglobin concentration. In the index case, midodrine treatment resulted in resolution of the hypotension and erythrocytosis. Most of the patients had multiple acquired renal cysts, which is a potential source of erythropoietin. Four of the five cases developed arteriovenous dialysis access or deep venous thrombosis. CONCLUSIONS: An association between intradialytic hypotension and erythrocytosis was observed in five cases. We postulate that chronic intermittent hypotension and renal ischemia may lead to erythropoietin secretion, and this cascade could represent a newly recognized cause of secondary erythrocytosis.

Clinician dashboard views and improvement in preventative health outcome measures: a retrospective analysis.

BACKGROUND: Measuring and reporting outcome data is fundamental for health care systems to drive improvement. Our electronic health record built a dashboard that allows each primary care provider (PCP) to view real-time population health quality data of their patient panel and use that information to identify care gaps. We hypothesized that the number of dashboard views would be positively associated with clinical quality improvement. METHODS: We performed a retrospective analysis of change in quality scores compared to number of dashboard views for each PCP over a five-month period (2017-18). Using the manager dashboard, we recorded the number of views for each provider. The quality scores analyzed were: colorectal cancer (CRC) screening rates and diabetic patients with an A1c greater than 9% or no A1c in the past year. RESULTS: Data from 120 PCPs were included. The number of dashboard views by each PCP ranged from 0 to 222. Thirty-one PCPs (25.8%) did not view their dashboard. We found no significant correlation between views and change in quality scores (correlation coefficient = 0.06, 95% CI [- 0.13, 0.25] and - 0.05, 95% CI [- 0.25, 0.14] for CRC and diabetes, respectively). CONCLUSION: Clinical dashboards provide feedback to PCPs and are likely to become more available as healthcare systems continue to focus on improving population health. However, dashboards on their own may not be sufficient to impact clinical quality improvement. Dashboard viewership did not appear to impact clinician performance on quality metrics.

Functional health status of adults with serious mental illness and diabetes mellitus: A latent profile analysis.

OBJECTIVE: Adults with serious mental illness are at increased risk for diabetes mellitus and diabetes-related complications. This article classifies subgroups among people with serious mental illness and comorbid diabetes with respect to functional status and examines differences among those groups. METHODS: This analysis used a baseline sample of 157 adults with serious mental illness and diabetes mellitus enrolled in a National Institute of Health-funded research study. Latent profile analysis was used to distinguish health status profiles and investigate how these subgroups differed across assessment domains. RESULTS: Participants with depression, schizophrenia, and bipolar disorder (n = 157) were included in the study. Mean age was 52.9 years (standard deviation = 9.8), and 62 (40%) were African American. From the latent profile analysis, a three-class model appeared to provide the best fit. Class 1 (34.9%) had a very low functional health status approximately two standard deviations below the general population mean. Class 2 (43.7%) had a low functional status approximately one standard deviation below the general mean. Class 3 (21.4%) had moderate functional status with scores near population mean. Groups differed on measures of personal characteristics, clinical status and symptom severity, self-care behaviors, and environmental characteristics. CONCLUSIONS: Although individuals with schizophrenia generally have poor prognosis once they develop diabetes, latent profile analysis identified distinct health status subgroups. Although all three groups demonstrated illness burden, the pattern of differences between these groups across measures may suggest the need for different interventions for highly diverse adults who received care within safety-net primary care.

Panel Size, Clinician Time in Clinic, and Access to Appointments.

Large panel sizes are often held responsible for worse access to appointments in primary care. We evaluated the relationship between appointment backlog, panel size, and primary care clinician time in clinic, using Spearman correlation and multiple regression in a retrospective analysis. We found no independent association between panel size and days until third next available appointment, but larger panel size adjusted for clinician time in clinic was associated with worse access. Less clinician time in clinic was independently associated with longer backlogs for appointments. Our findings suggest that patients of part-time clinicians may be less likely to obtain timely appointments than patients of fulltime clinicians, regardless of panel size.

Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: Findings from an interventional randomized controlled trial.

Objective Serious mental illness and type II diabetes mellitus have a high comorbidity, and both have a higher prevalence of anxiety disorders compared to the general population. Targeted Training in Illness Management is a group-based self-management training approach which targets serious mental illness and type II diabetes mellitus concurrently. This analysis examines data from a randomized controlled trial of Targeted Training in Illness Management intervention to examine the impact of comorbid anxiety on baseline psychiatric symptomatology and diabetic control, and on longitudinal treatment outcomes. Methods We conducted secondary analyses on data from a prospective, 60-week, randomized controlled trial testing Targeted Training in Illness Management versus treatment as usual in 200 individuals with serious mental illness and diabetes. Primary outcomes included measures related to serious mental illness symptoms, functional status, general health status, and diabetes control. Measures were compared between those participants with anxiety disorders versus those without anxiety at baseline as well as over time using linear mixed effects analyses. Results Forty seven percent of the participants had one or more anxiety disorders. At baseline, those with an anxiety diagnosis had higher illness severity, depressive, and other psychiatric symptomatology and disability. Diabetic control (HbA1c) was not significantly different at baseline. In the longitudinal analyses, no significant mean slope differences over time (group-by-time interaction effect) between those with anxiety diagnoses and those without in treatment as usual group were found for primary outcomes. Within the Targeted Training in Illness Management arm, those with anxiety disorders had significantly greater improvement in mental health functioning. Those with anxiety comorbidity in the Targeted Training in Illness Management group demonstrated significantly lower HbA1c levels compared to no anxiety comorbidity and also demonstrated a greater improvement in HbA1c over the first 30 weeks compared to those without anxiety comorbidity. Conclusion Comorbid anxiety in serious mental illness and type II diabetes mellitus population is associated with increased psychiatric symptomatology and greater disability. Individuals from this population appear to experience greater improvement in functioning from baseline with the Targeted Training in Illness Management intervention. Anxiety comorbidity in the serious mental illness and type II diabetes mellitus population does not appear to have a negative impact on diabetic control. These complex relationships need further study. Clinical Trials Registration ClinicalTrials.gov: Improving outcomes for individuals with serious mental illness and diabetes (NCT01410357).

Smokers with MS have greater decrements in quality of life and disability than non-smokers.

BACKGROUND: Tobacco smoke plays a pathogenic role in multiple sclerosis (MS) and may accelerate disease progression, yet, some people with MS continue to smoke after disease onset. The average smoker reports diminished health-related quality of life (HRQOL) across many populations. OBJECTIVES: To describe the relationships between smoking status and HRQOL, disease activity, and global disability in a US population with MS. METHODS: We compared smokers to non-smokers in 950 responders to the Spring 2014 update survey completed by North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants. HRQOL was assessed using Short Form-12 version 2 (SF-12v2), disease activity was investigated using eight Performance Scales (PS) and three Functionality Scales (FS). Global disability was evaluated using Patient Determined Disease Steps (PDDS) and an item response theory (IRT) summed score based on the PS and FS. RESULTS: Smokers had lower HRQOL ( p < 0.0001), reported more disease activity ( p < 0.05) and greater deficits in all PS and FS ( p = 6 × 10-7 to 0.05), except mobility. Smokers and non-smokers did not differ by PDDS but had substantially greater IRT global disability ( p = 2 × 10-7). CONCLUSION: Active smoking is meaningfully associated with deficits across multiple domains in people with MS and adds to the growing literature of the need for MS-tailored smoking cessation programs.

Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis: A Randomized Trial.

BACKGROUND AND PURPOSE: It is unknown whether one method of neuromuscular electrical stimulation for poststroke upper limb rehabilitation is more effective than another. Our aim was to compare the effects of contralaterally controlled functional electrical stimulation (CCFES) with cyclic neuromuscular electrical stimulation (cNMES). METHODS: Stroke patients with chronic (>6 months) moderate to severe upper extremity hemiparesis (n=80) were randomized to receive 10 sessions/wk of CCFES- or cNMES-assisted hand opening exercise at home plus 20 sessions of functional task practice in the laboratory for 12 weeks. The task practice for the CCFES group was stimulation assisted. The primary outcome was change in Box and Block Test (BBT) score at 6 months post treatment. Upper extremity Fugl-Meyer and Arm Motor Abilities Test were also measured. RESULTS: At 6 months post treatment, the CCFES group had greater improvement on the BBT, 4.6 (95% confidence interval [CI], 2.2-7.0), than the cNMES group, 1.8 (95% CI, 0.6-3.0), between-group difference of 2.8 (95% CI, 0.1-5.5), P=0.045. No significant between-group difference was found for the upper extremity Fugl-Meyer (P=0.888) or Arm Motor Abilities Test (P=0.096). Participants who had the largest improvements on BBT were <2 years post stroke with moderate (ie, not severe) hand impairment at baseline. Among these, the 6-month post-treatment BBT gains of the CCFES group, 9.6 (95% CI, 5.6-13.6), were greater than those of the cNMES group, 4.1 (95% CI, 1.7-6.5), between-group difference of 5.5 (95% CI, 0.8-10.2), P=0.023. CONCLUSIONS: CCFES improved hand dexterity more than cNMES in chronic stroke survivors. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00891319.

Clinical Indicators of Late-Onset Sepsis Workup in Very Low-Birth-Weight Infants in the Neonatal Intensive Care Unit.

Background Late-onset sepsis (LOS) in very low-birth-weight (VLBW) infants is associated with significant morbidity and mortality. Objectives To determine the incidence of LOS workup, association, and predictive value of clinical indicators leading to culture-positive versus culture-negative sepsis workup. Methods All sepsis workups performed after 7 days of life, in neonates with birth weight of < 1,500 g were included. Each case (culture-positive workup) was matched with a control (culture-negative workup) for gestational age (GA), birth weight, corrected gestational age, and chronological age, at the time of workup. The clinical indicators leading to the performance of sepsis workup were compared between cases and controls. Results The incidence of culture-positive workup was 87/345 (25.2%) and that of LOS was 84/279 (30.1%). Among various clinical indicators, hypothermia and apnea were significantly associated with culture-positive sepsis workup (p = 0.015 and 0.004, respectively), with a positive predictive value of 81.2 and 71.4%, respectively. Conclusion In VLBW infants, one-fourth of sepsis workups resulted in a positive culture. Apnea and hypothermia were the most significant predictors of culture-positive workup after matching for GA, birth weight, chronological age, and corrected GA at the time of the workup.

A Preliminary Analysis of Individuals With Serious Mental Illness and Comorbid Diabetes.

OBJECTIVE: To understand factors related to managing illness in older individuals with serious mental illness (SMI). METHODS: Baseline data from 200 individuals with SMI and diabetes enrolled in a study were used to compare characteristics between older (age >55) vs. younger (age ≤55) individuals. RESULTS: Older individuals had better diabetes control compared to younger individuals, those with major depressive disorder had diabetes for a longer duration, worse diabetic control, and more emergency department encounters. CONCLUSIONS: Helping younger individuals with SMI learn to manage their mental and physical health early-on might minimize the negative and cumulative effect of diabetes.

Effects of Patient Centered Interventions on Persistent Urinary Incontinence after Prostate Cancer Treatment: A Randomized, Controlled Trial.

PURPOSE: We examined whether an intervention combining pelvic floor muscle exercise and symptom self-management would improve urinary continence and quality of life in patients with prostate cancer. MATERIALS AND METHODS: In a randomized, controlled, longitudinal clinical trial 279 patients with prostate cancer with persistent urinary incontinence were randomized to 1 of 3 groups, including biofeedback pelvic floor muscle exercise plus a support group, the biofeedback exercise plus telephone contact and usual care without intervention. The biofeedback plus support and plus telephone groups received 1 session of biofeedback assisted exercise and 6 biweekly sessions of problem solving therapy. This delivered symptom management skills through a peer support group or telephone contacts for 3 months. All subjects were assessed in blinded fashion at baseline, and 3 and 6 months for urinary leakage frequency, leakage amount and disease specific quality of life. RESULTS: A total of 244 subjects completed the study. The biofeedback plus support and biofeedback plus telephone groups had a lower frequency of daily urinary leakage than the group with usual care without intervention at 3 months (p=0.019 and p≤0.001, respectively) but not at 6 months. The biofeedback plus support group but not the biofeedback plus telephone group had 13.3 gm lower leakage at 6 months than the usual care group (p=0.003). Overall the biofeedback plus support and plus telephone groups reported less symptom severity (p≤0.001) and fewer incontinence problems (p≤0.01) than the usual care group at 6 months. CONCLUSIONS: Study findings show that pelvic floor muscle exercise practice plus symptom self-management in a peer support setting can significantly improve urinary continence and quality of life in patients with prostate cancer.

A tutorial on structural equation modeling for analysis of overlapping symptoms in co-occurring conditions using MPlus.

Structural equation modeling (SEM) is a very general approach to analyzing data in the presence of measurement error and complex causal relationships. In this tutorial, we describe SEM, with special attention to exploratory factor analysis, confirmatory factor analysis, and multiple indicator multiple cause modeling. The tutorial is motivated by a problem of symptom overlap routinely faced by clinicians and researchers, in which symptoms or test results are common to two or more co-occurring conditions. As a result of such overlap, diagnoses, treatment decisions, and inferences about the effectiveness of treatments for these conditions can be biased. This problem is further complicated by increasing reliance on patient-reported outcomes, which introduces systematic error based on an individual's interpretation of a test questionnaire. SEM provides flexibility in handling this type of differential item functioning and disentangling the overlap. Scales and scoring approaches can be revised to be free of this overlap, leading to better care. This tutorial uses an example of depression screening in multiple sclerosis patients in which depressive symptoms overlap with other symptoms, such as fatigue, cognitive impairment, and functional impairment. Details of how MPlus (Muthén & Muthén, Los Angeles, CA, USA) software can be used to address the symptom overlap problem, including data requirements, code and output are described in this tutorial.

On performance of parametric and distribution-free models for zero-inflated and over-dispersed count responses.

Zero-inflated Poisson (ZIP) and negative binomial (ZINB) models are widely used to model zero-inflated count responses. These models extend the Poisson and negative binomial (NB) to address excessive zeros in the count response. By adding a degenerate distribution centered at 0 and interpreting it as describing a non-risk group in the population, the ZIP (ZINB) models a two-component population mixture. As in applications of Poisson and NB, the key difference between ZIP and ZINB is the allowance for overdispersion by the ZINB in its NB component in modeling the count response for the at-risk group. Overdispersion arising in practice too often does not follow the NB, and applications of ZINB to such data yield invalid inference. If sources of overdispersion are known, other parametric models may be used to directly model the overdispersion. Such models too are subject to assumed distributions. Further, this approach may not be applicable if information about the sources of overdispersion is unavailable. In this paper, we propose a distribution-free alternative and compare its performance with these popular parametric models as well as a moment-based approach proposed by Yu et al. [Statistics in Medicine 2013; 32: 2390-2405]. Like the generalized estimating equations, the proposed approach requires no elaborate distribution assumptions. Compared with the approach of Yu et al., it is more robust to overdispersed zero-inflated responses. We illustrate our approach with both simulated and real study data.