J. Richard Landis

University of Pennsylvania | UP · Department of Biostatistics and Epidemiology

Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the lik...

Purpose In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only. Materials and Methods A 76‐site body map was administered four times, at weekly in...

Purpose This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM). Materials and Methods A previously valid...

We pay tribute to Marshall Joffe, PhD, and his substantial contributions to the field of causal inference with focus in biostatistics and epidemiology. By compiling narratives written by us, his colleagues, we not only present highlights of Marshall’s research and their significance for causal inference but also offer a portrayal of Marshall’s pers...

Objectives: Symptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urologic chronic pelvic pain syndrome (UCPPS), has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences (CIDs) for 2 primary sym...

Clinical trials of pain are notoriously difficult and inefficient in demonstrating efficacy even for known efficacious treatments. Determining the appropriate pain phenotype to study can be problematic. Recent work has identified the extend of widespread pain as an important factor in the likelihood of response to therapy, but has not been tested i...

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the Multidisciplinary Approach to the study of chronic Pelvic Pain (MAPP) research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more s...

By clustering patients with the urologic chronic pelvic pain syndromes (UCPPS) into homogeneous subgroups and associating these subgroups with baseline covariates and other clinical outcomes, we provide opportunities to investigate different potential elements of pathogenesis, which may also guide us in selection of appropriate therapeutic targets....

Purpose: We assessed the reliability and validity of an efficient severity assessment for pelvic pain and urinary symptoms in urological chronic pelvic pain syndrome, which consists of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. Materials and methods: A total of 578 patients were assessed usi...

Objective To examine how often urologic chronic pelvic pain syndrome (UCPPS) patients progressed from Pelvic Pain Only at baseline to Widespread Pain, or vice versa, during one-year longitudinal follow-up. Methods Men and women with UCPPS enrolled in the MAPP-I Epidemiology and Phenotyping Study completed a self-report body map to indicate their l...

Objective: To use the phenotyping data from the MAPP-II Symptom Patterns Study (SPS) to compare the systemic features between urologic chronic pelvic pain syndrome (UCPPS) with Hunner lesion (HL) versus those without HL. Methods: We performed chart review on 385 women and 193 men with UCPPS who enrolled in the MAPP-II SPS. 223 had cystoscopy and...

Background CKD is a heterogeneous condition with multiple underlying causes, risk factors, and outcomes. Subtyping CKD with multidimensional patient data holds the key to precision medicine. Consensus clustering may reveal CKD subgroups with different risk profiles of adverse outcomes. Methods We used unsupervised consensus clustering on 72 baseli...

Background The intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in pati...

Neural circuitry regulating urine storage in humans has been largely inferred from fMRI during urodynamic studies driven by catheter infusion of fluid into the bladder. However, urodynamic testing may be confounded by artificially filling the bladder repeatedly at a high rate and examining associated time-locked changes in fMRI signals. Here we des...

Background Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown. Methods Single-center, randomized, placebo-controlled, double-blind pilot trial to explore safety and tolerability of ISD/HY in maintenan...

Aims The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study—the Symptom Patterns Study (SPS)—to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and...

Purpose: To evaluate and identify baseline factors associated with change in health-related quality of life (HRQOL) among patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: A total of 191 men and 233 women with IC/BPS or CP/CPPS (collectively referred to as...

Purpose To correlate the presence of fungi with symptom flares, pain and urinary severity in a prospective, longitudinal study of women with IC/BPS enrolled in the MAPP Research Network. Methods Flare status, pelvic pain, urinary severity, and midstream urine were collected at baseline, 6 and 12 months from female IC/BPS participants with at least...

Abstract Experimental pain sensitivity was assessed in individuals with urologic chronic pelvic pain syndrome (UCPPS) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. A series of computer-controlled pressure stimuli were delivered to the thumbnail bed, an asymptomatic site distant from the area...

Objective To describe the frequency, intensity and duration of urological chronic pelvic pain syndrome symptom exacerbations (‘flares’), as well as risk factors for these features, in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Epidemiology and Phenotyping longitudinal study. Participants and Methods Current flare status (‘u...

Background: Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established. Methods: To develop approaches for embedding trials into routine deli...

Abstract: We surveyed urine microbiota of females diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) and matched control participants enrolled in the National Institutes of Health (NIH) Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network using the culture-independent methodology. Midstream urine s...

Background Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resi...

Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk...

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network has yielded neuroimaging and urinary biomarker findings that highlight unique alterations in brain structure and in urinary proteins related to tissue remodeling and vascular structure in patients with Urological Chronic Pelvic Pain Syndrome (UCPPS). We hypot...

The safety and efficacy of spironolactone is uncertain in end-stage renal disease. We randomized 129 maintenance hemodialysis patients to placebo (n=51) or spironolactone 12.5 mg (n=27), 25 mg (n=26), or 50 mg (n=25) daily for 36 weeks in a double-blind, placebo-controlled, multiple dosage trial to assess safety, tolerability and feasibility and to...

Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This 'centralized pain' phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensa...

Background Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and bereavement have been linked to number of chronic pain conditions in adulthood, and specifically to urologic chronic pelvic pain syndrome (UCPPS). Purpose We sought to characterize the prevalence of ACEs in UCPPS using a large well-characteri...

Purpose: We examined health-care seeking activities over a 12-month period in a cohort of men and women with urological chronic pelvic pain syndromes (UCPPS). Materials and methods: A total of 191 men and 233 women with UCPPS were followed with biweekly internet-based questionnaires about their symptoms and health-care seeking (HCS) activities,...

Purpose: Although many factors have been proposed to trigger symptom exacerbations ("flares") in patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, few studies have investigated these factors empirically. Therefore, we embedded a case-crossover study in the Multidisciplinary Approach to...

When estimating the effect of an exposure on a time-to-event type of outcome, one can focus on the baseline exposure or the time-updated exposures. Cox regression models can be used in both situations. When time-dependent confounding exists, the Cox model with time-updated covariates may produce biased effect estimates. Marginal structural models,...

Repeated measures of various biomarkers provide opportunities for us to enhance understanding of many important clinical aspects of CKD, including patterns of disease progression, rates of kidney function decline under different risk factors, and the degree of heterogeneity in disease manifestations across patients. However, because of unique featu...

Cardiovascular events, such as hospitalizations because of congestive heart failure, often occur repeatedly in patients with CKD. Many studies focus on analyses of the first occurrence of these events, and discard subsequent information. In this article, we review a number of statistical methods for analyzing ordered recurrent events of the same ty...

Chronic pain is often measured with a severity score that overlooks its spatial distribution across the body. This widespread pain is thought to be a marker of centralization, a central nervous system process that decouples pain perception from nociceptive input. Here, we investigated whether centralization is manifested at the level of the brain u...

Objective: To examine baseline clinical and psychosocial characteristics that predict 12- month symptom change in men and women with urologic chronic pelvic pain syndromes (UCPPS). Methods: 221 female and 176 male UCPPS patients were recruited from 6 academic medical centers in the United States and evaluated at baseline with a comprehensive bat...

Purpose: We characterized the location and spatial distribution of whole body pain among patients with urologic chronic pelvic pain syndrome (UCPPS) using a body map; and compared the severity of urinary symptoms, pelvic pain, non-pelvic pain, and psychosocial health among patients with different pain patterns. Methods: 233 women and 191 men wit...

Objective: To date, no definitive, broadly accepted biomarkers for UCPPS have been identified. The present study examines a series of candidate markers for UCPPS selected based on proposed involvement in underlying biological processes and is intended to provide new insights into pathophysiology and suggest targets for expanded clinical and mechan...

Chronic pain symptoms often change over time, even in individuals who have had symptoms for years. Studying biological factors that predict trends in symptom change in chronic pain may uncover novel pathophysiological mechanisms and potential therapeutic targets. In this study, we investigated whether brain functional connectivity measures obtained...

Survival analysis is commonly used to evaluate factors associated with time to an event of interest (e.g., ESRD, cardiovascular disease, and mortality) among CKD populations. Time to the event of interest is typically observed only for some participants. Other participants have their event time censored because of the end of the study, death, withd...

Prediction models are often developed in and applied to CKD populations. These models can be used to inform patients and clinicians about the potential risks of disease development or progression. With increasing availability of large datasets from CKD cohorts, there is opportunity to develop better prediction models that will lead to more informed...

Targeting couples is a promising behavioral HIV risk-reduction strategy, but the mechanisms underlying the effects of such interventions are unknown. We report secondary analyses testing whether Social-Cognitive-Theory variables mediated the Eban HIV-risk-reduction intervention's effects on condom-use outcomes. In a multisite randomized controlled...

Introduction: We examine symptom variability in men and women with urological chronic pelvic pain syndrome (UCPPS). We describe symptom fluctuations as related to early symptom regression and its effect on estimated one-year symptom change. We then describe a method to quantify patient-specific symptom variability. Methods: Symptoms were assesse...

Background Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. Methods We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone g...

Purpose: The purpose of this study was to create symptom indexes, that is scores derived from questionnaires to accurately and efficiently measure symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urological chronic pelvic pain syndromes. We created these index...

Studies have suggested chronic pain syndromes are associated with neural reorganization in specific regions associated with perception, processing, and integration of pain. Urological chronic pelvic pain syndrome (UCPPS) represents a collection of pain syndromes characterized by pelvic pain, namely Chronic Prostatitis/Chronic Pelvic Pain Syndrome (...

Purpose: We compared culture-independent assessment of microbiota of the lower urinary tract in standard culture negative female UCPPS patients who reported symptom flare to those who did not report a flare. Materials and methods: Initial stream (VB1) and midstream (VB2) urine specimens (n=233 UCPPS patients) were analyzed with Ibis T-5000 Unive...

To describe bladder-associated symptoms in patients with urologic chronic pelvic pain syndromes (UCPPS) and to correlate these symptoms with urologic, non-urologic, psychosocial, and quality of life measures. Participants were 233 women and 191 men with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome...

We used next-generation, state-of-the-art, culture-independent methodology to survey urine microbiota of UCPPS males and control participants enrolled in the MAPP Network to investigate a possible microbial etiology. Male UCPPS patients and matched controls were asked to provide VB1, VB2 and VB3 urine specimens. Specimens were analyzed with Ibis T-...

The clinical features of interstitial cystitis/ bladder pain syndrome (IC/BPS) are similar to those of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have directly compared the characteristics of these syndromes in men and women. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research netw...

We report data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) network to: (1) identify participants having either (a) urologic chronic pelvic pain syndromes (UCPPS) only or (b) chronic functional non-urological associated somatic syndromes (NUAS) in addition to UCPPS, (2) characterize these two subgroups, and (3) exp...

Purpose: To examine whether an Internet-based learning module and small-group debriefing can improve medical trainees' attitudes and communication skills toward patients with substance use disorders (SUDs). Method: In 2011-2012, 129 internal and family medicine residents and 370 medical students at two medical schools participated in a cluster r...

We are motivated by a randomized clinical trial evaluating the efficacy of amitriptyline for the treatment of interstitial cystitis and painful bladder syndrome in treatment-naïve patients. In the trial, both the non-adherence rate and the rate of loss to follow-up are fairly high. To estimate the effect of the treatment received on the outcome, we...

Urologic chronic pelvic pain syndrome (UCPPS) may be defined to include interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The hallmark symptom of UCPPS is chronic pain in the pelvis, urogenital floor, or external genitalia often accompanied by lower urinary tract symptoms. Despite n...

Background The “Multidisciplinary Approach to the Study of Chronic Pelvic Pain” (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Res...

High ambient temperatures are a risk factor for nephrolithiasis, but the precise relationship between temperature and kidney stone presentation is unknown. OBJECTIVES Our objective was to estimate associations between mean daily temperature and kidney stone presentation according to lag time and temperatures. METHODS Using a time series design...

METHODS: This study includes 12 questionnaires completed within one month prior to RC. Using the EORTC scores, a hierarchical cluster analysis was carried out to identify clusters. Stopping rules were explored based on the recommended number of clusters; after considerations we opted for a 3-cluster solution. Clusters were then compared for demogra...

Rationale: Twenty-eight percent of people with mild to moderate obstructive sleep apnea experience daytime sleepiness, which interferes with daily functioning. It remains unclear whether treatment with continuous positive airway pressure improves daytime function in these patients. Objectives: To evaluate the efficacy of continuous positive airw...

Glomerular filtration rate (GFR) is considered the best measure of kidney function, but repeated assessment is not feasible in most research studies. Cross-sectional study of 1,433 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (ie, the GFR subcohort) to derive an internal GFR estimating equation using a split-sample approach....

We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical ce...

Identification of the characteristics that put hospitalized children at high risk of deterioration may help to target patients whose physiologic status should be intensively monitored for signs of deterioration, and reduce unnecessary monitoring in patients at very low risk. Previous studies have evaluated vital sign-based early warning scores to d...

A new model for the conduct of clinical research was established at the University of Pennsylvania (Penn) School of Medicine, now the Perelman School of Medicine, through the development of the interdepartmental Center for Clinical Epidemiology and Biostatistics in 1993 and the basic science Department of Biostatistics and Epidemiology in 1994. The...

The prevalence of obesity and urolithiasis in children has increased with time. We evaluated the relationship between body mass and urolithiasis in children. We performed a matched case-control study in a network of 30 primary care pediatric practices. Cases included subjects with ICD-9 codes for urolithiasis and controls were matched on age, durat...

This article reviews measures of interrater agreement, including the complementary roles of tests for interrater bias and estimates of kappa statistics and intraclass correlation coefficients (ICCs), following the developments outlined by Landis and Koch (1977a; 1977b; 1977c). Category-specific measures of reliability, together with pairwise measur...

The high morbidity and mortality in African Americans associated with behavior-linked chronic diseases are well documented. We tested the efficacy of an intervention to increase multiple health-related behaviors in African Americans. In a multisite cluster-randomized controlled trial, groups of African American human immunodeficiency virus (HIV)-se...

We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome. A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at le...