Ponsegromab for the Treatment of Cancer Cachexia.

BACKGROUND: Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels. METHODS: In this phase 2, randomized, double-blind, 12-week trial, we assigned patients with cancer cachexia and an elevated serum GDF-15 level (≥1500 pg per milliliter) in a 1:1:1:1 ratio to receive ponsegromab at a dose of 100 mg, 200 mg, or 400 mg or to receive placebo, administered subcutaneously every 4 weeks for three doses. The primary end point was the change from baseline in body weight at 12 weeks. Key secondary end points were appetite and cachexia symptoms, digital measures of physical activity, and safety. RESULTS: A total of 187 patients underwent randomization. Of these patients, 40% had non-small-cell lung cancer, 32% had pancreatic cancer, and 29% had colorectal cancer. At 12 weeks, patients in the ponsegromab groups had significantly greater weight gain than those in the placebo group, with a median between-group difference of 1.22 kg (95% credible interval, 0.37 to 2.25) in the 100-mg group, 1.92 (95% credible interval, 0.92 to 2.97) in the 200-mg group, and 2.81 (95% credible interval, 1.55 to 4.08) in the 400-mg group. Improvements were observed across measures of appetite and cachexia symptoms, along with physical activity, in the 400-mg ponsegromab group relative to placebo. Adverse events of any cause were reported in 70% of the patients in the ponsegromab group and in 80% of those in the placebo group. CONCLUSIONS: Among patients with cancer cachexia and elevated GDF-15 levels, the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, findings that confirmed the role of GDF-15 as a driver of cachexia. (Funded by Pfizer; ClinicalTrials.gov number, NCT05546476.).

Adaptation and validation of the Treatment Burden Questionnaire (TBQ) in English using an internet platform.

BACKGROUND: Treatment burden refers to the workload imposed by healthcare on patients, and the effect this has on quality of life. The Treatment Burden Questionnaire (TBQ) aims to assess treatment burden in different condition and treatment contexts. Here, we aimed to evaluate the validity and reliability of an English version of the TBQ, a scale that was originally developed in French. METHODS: The TBQ was translated into English by a forward-backward translation method. Wording and possible missing items were assessed during a pretest involving 200 patients with chronic conditions. Measurement properties of the instrument were assessed online with a patient network, using the PatientsLikeMe website. Dimensional structure of the questionnaire was assessed by factor analysis. Construct validity was assessed by associating TBQ global score with clinical variables, adherence to medication assessed by Morisky's Medication Adherence Scale (MMAS-8), quality of life (QOL) assessed by the PatientsLikeMe Quality of Life Scale (PLMQOL), and patients' confidence in their knowledge of their conditions and treatments. Reliability was determined by a test-retest method. RESULTS: In total, 610 patients with chronic conditions, mainly from the USA, UK, Canada, Australia, or New Zealand, completed the TBQ between September and October 2013. The English TBQ showed a unidimensional structure with Cronbach α of 0.90. The TBQ global score was negatively correlated with the PLMQOL score (rs = -0.50; p < 0.0001). Low rather than moderate or high adherence to medication was associated with high TBQ score (mean [SD] TBQ score 61.8 [30.5] vs. 37.7 [27.5]; P < 0.0001). The treatment burden was higher for patients who had insufficient knowledge compared with those who had sufficient knowledge about their treatments (mean ± SD TBQ score 62.3 ± 31.3 vs. 47.8 ± 30.4; P < 0.0001) and conditions (63.0 ± 31.6 vs. 49.3 ± 30.7; P < 0.0001). The intraclass correlation coefficient for the retest (n = 282) was 0.77 (95% CI 0.70 to 0.82). CONCLUSIONS: We found that the English TBQ is a reliable instrument in this population, and provide evidence supporting the construct validity for its use to assess treatment burden for patients with one or more chronic conditions in English-speaking countries.

A Phase Ib First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia.

PURPOSE: Cachexia is common in patients with advanced cancer and is associated with elevated serum growth differentiation factor 15 (GDF-15) concentrations. This first-in-patient (phase Ib), 24-week study assessed use of ponsegromab, a mAb against GDF-15, in adults with advanced cancer, cachexia, and elevated GDF-15 serum concentration. PATIENTS AND METHODS: Participants (n = 10) received open-label ponsegromab subcutaneous 200 mg every 3 weeks for 12 weeks in addition to standard-of-care anticancer treatment. Ponsegromab safety, tolerability, and pharmacokinetics were assessed in addition to serum GDF-15 concentrations and exploratory measures of efficacy. RESULTS: No treatment-related treatment-emergent adverse events, injection site reactions, or adverse trends in clinical laboratory tests, vital signs, or electrocardiogram parameters attributable to ponsegromab were identified. Median serum unbound GDF-15 concentration at baseline was 2.269 ng/mL. Following initiation of study treatment, median unbound GDF-15 concentrations were below the lower limit of quantification (0.0424 ng/mL) from day 1 (3 hours postdose) through week 15. Increases in body weight were observed at all time points during the treatment and follow-up periods. A least-squares mean (SE) increase of 4.63 (1.98) kg was observed at week 12, an increase of approximately 6.6% relative to baseline. Ponsegromab-mediated improvements in actigraphy-based assessments of physical activity and in quality of life, including appetite as assessed by Functional Assessment of Anorexia-Cachexia Therapy total and subscale scores, were also observed. CONCLUSIONS: Ponsegromab was well tolerated, suppressed serum GDF-15 concentrations, and demonstrated preliminary evidence of efficacy. These findings support the continued development of ponsegromab for the treatment of cachexia.

Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.

BACKGROUND: Cancer cachexia is a multifactorial metabolic wasting syndrome characterized by anorexia, unintentional loss of weight involving both skeletal muscle and adipose tissues, progressive functional impairment and reduced survival. Therapeutic strategies for this serious condition are very limited. Growth differentiation factor 15 (GDF-15) is a cytokine that is implicated in cancer cachexia and may represent both a biomarker of cancer cachexia and a potential therapeutic target. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF-15-mediated signalling. Preclinical and preliminary phase 1 data suggest that ponsegromab-mediated inactivation of circulating GDF-15 may lead to improvement in key characteristics of cachexia. The primary objective of this phase 2 study is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia and elevated GDF-15 concentrations. Secondary objectives include assessing physical activity, physical function, actigraphy, appetite, nausea and vomiting, fatigue and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, immunogenicity, lumbar skeletal muscle index and Response Evaluation Criteria in Solid Tumors. METHODS: Approximately 168 adults with non-small-cell lung, pancreatic or colorectal cancers who have cachexia and elevated GDF-15 concentrations will be randomized in a double-blind, placebo-controlled study (NCT05546476). Participants meeting eligibility criteria will be randomized 1:1:1:1 to one of three dose groups of ponsegromab (100, 200 or 400 mg) or matching placebo administered subcutaneously every 4 weeks for an initial 12-week treatment period. This is followed by optional open-label treatment with ponsegromab of 400 mg administered every 4 weeks for up to 1 year. The primary endpoint is mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian Emax model will be used for the primary analysis. Secondary endpoints include physical activity, physical function and actigraphy measured by remote digital sensors; patient-reported appetite-related symptoms assessed by Functional Assessment of Anorexia-Cachexia Therapy subscale scores; anorexia/appetite, nausea and vomiting, and fatigue evaluated according to questions from the Cancer-Related Cachexia Symptom Diary; and incidence of adverse events, safety laboratory tests, vital signs and electrocardiogram abnormalities. PERSPECTIVE: Cancer-related cachexia is an area of significant unmet medical need. This study will support the clinical development of ponsegromab as a novel inhibitor of GDF-15, which may ameliorate key pathologies of cancer cachexia to improve patient symptoms, functionality and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05546476.

Parole officer-parolee relationships and HIV risk behaviors during community supervision.

We tested if good parole officer (PO)-parolee relationships reduce HIV risk behaviors during parole, as they do for risk of rearrest. Analyses used data from 374 parolees enrolled in a randomized clinical trial. Past month HIV risk behaviors were assessed by interview at baseline, 3- and 9-months after parole initiation. The Working Alliance Inventory and the Dual-Role Relationships Inventory measured PO relationship. Gender-stratified multivariate regressions tested associations of PO-parolee relationship with sex with multiple partners, unprotected sex with risky partner(s), and drug injection. Women parolees (n = 65) who reported better PO relationship characteristics were less likely to report having multiple sex partners [adjusted odds ratio: 0.82 (0.69, 0.98) at 3-months, 0.89 (0.80, 0.99) at 9-months], and, among those reporting multiple sex partners, had fewer partners on average [adjusted relative risk 0.98 (0.96, 0.99)]. These effects were not found among men. PO-parolee relationship quality can influence sexual risk behaviors among women parolees.

Limiting options: sex ratios, incarceration rates, and sexual risk behavior among people on probation and parole.

BACKGROUND: To investigate how incarceration may affect risk of acquiring HIV and other sexually transmitted infections, we tested associations of ex-offenders' sexual risk behavior with the male-female sex ratio and the male incarceration rate. METHODS: Longitudinal data from 1287 drug-involved persons on probation and parole as part of the Criminal Justice Drug Abuse Treatment Studies were matched by county of residence with population factors, and stratified by race/ethnicity and gender. Generalized estimating equations assessed associations of having unprotected sex with a partner who had HIV risk factors, and having >1 sex partner in the past month. RESULTS: Among non-Hispanic black men and women, low sex ratios were associated with greater risk of having unprotected sex with a risky partner (adjusted relative risk [ARR] = 1.76, 95% confidence interval [CI] = 1.29, 2.42; ARR = 2.48, 95% CI = 1.31, 4.73, respectively). Among non-Hispanic black and non-Hispanic white (NHW) women, low sex ratios were associated with having >1 sex partner (ARR = 2.00, 95% CI = 1.02, 3.94; ARR = 1.71, 95% CI = 1.06, 2.75, respectively). High incarceration rates were associated with greater risk of having a risky partner for all men (non-Hispanic black: ARR = 2.14, 95% CI = 1.39, 3.30; NHW: ARR = 1.39, 95% CI: 1.05, 1.85; Hispanic: ARR = 3.99, 95% CI = 1.55, 10.26) and having >1 partner among NHW men (ARR = 1.92, 95% CI = 1.40, 2.64). CONCLUSIONS: Low sex ratios and high incarceration rates may influence the number and risk characteristics of sex partners of ex-offenders. HIV-prevention policies and programs for ex-offenders could be improved by addressing structural barriers to safer sexual behavior.

SIBAT-A Computerized Assessment Tool for Suicide Ideation and Behavior: Development and Psychometric Properties.

Objective: Most assessments of suicidal ideation and behavior (SIB) are limited by reliance on a single assessor, typically a clinician or patient, with scant detail on patient-related drivers of SIB and inability to detect rapid change in SIB. Furthermore, many techniques do not include a semistructured interview, increasing rater variability. The Suicide Ideation and Behavior Assessment Tool (SIBAT) addresses these limitations. Design: More than 30 experts in scale development, statistics, and clinical management of suicidal patients collaborated over a greater than four-year period to develop the SIBAT. Input for content and validity was received from patients, clinicians, and regulatory authorities in the United States (US) and Europe. Psychometric properties of the SIBAT were evaluated in validation studies. Results: The SIBAT is organized into eight independent patient- or clinician-rated modules with branching logic and scoring algorithms, which necessitates computerization. Patient-reported information is first captured in Modules 1 to 5. Thereafter, an experienced clinician reviews the patient's report, conducts a semistructured interview (Module 6), and assesses the patient's suicide risk (Module 7) and optimal antisuicide management (Module 8). Input from cognitive interviews of diverse adult, adolescent, and clinician participants was incorporated into the final version of the SIBAT. Psychometric testing demonstrated good inter-rater reliability (intraclass coefficient range: 0.68-0.82), intra-rater reliability (weighted-kappa range: 0.64-0.76), and concurrent validity with other instruments for assessing SIB. Conclusion: Patient- and clinician-based assessments and the psychometric studies summarized in this report support the validity and reliability of the SIBAT for capturing critical information related to assessment of SIB in adolescents and adults at risk for suicide.

Projected Retained Ability Score (PRAS): A New Methodology for Quantifying Absolute Change in Norm-Based Psychological Test Scores Over Time.

A limitation of norm-based ability test scores is that they can only be used to evaluate relative change (compared with change in the norm sample), as opposed to absolute (raw) change in performance from Time 1 to Time 2. To address this limitation, a novel method (Projected Retained Ability Score [PRAS]) was developed to characterize absolute change in norm-based ability test scores. The PRAS method was applied to Differential Ability Scales®-Second Edition (DAS-II) General Conceptual Ability (GCA) scores in three cases of children with the neurodegenerative condition mucopolysaccharidosis type II (MPS II) who were assessed at two visits, 16 to 23 months apart. Although all three cases showed declines in norm-based GCA scores, the PRAS method revealed differences in absolute change in performance. The PRAS method allows for differentiation of slower-than-average improvement or stabilization versus deterioration of cognitive ability when norm-based scores decline from Time 1 to Time 2.

Analysis of cognitive ability and adaptive behavior assessment tools used in an observational study of patients with mucopolysaccharidosis II.

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by cognitive impairment in most patients. This post hoc analysis evaluated changes in cognitive function, adaptive behavior and functional outcomes in patients with neuronopathic MPS II over time. Fifty-five children with MPS II were enrolled in a 24-month observational study (NCT01822184). The Differential Ability Scales, second edition (DAS-II; early years battery for ages 2 years 6 months to 6 years 11 months, school age battery for ages 7 years to 17 years 11 months), Vineland Adaptive Behavior Scales, second edition (VABS-II) and the Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) were performed at baseline and 3-month intervals over 2 years. A subgroup of 38 children with a DAS-II General Conceptual Ability (GCA) score of 55-85 (below average-very low abilities) at any time during the study were included in this analysis. RESULTS: Mean (standard deviation [SD]) early years DAS-II GCA score decreased from 73.4 (15.7, n = 22) at baseline to 62.7 (34.9, n = 6) at month 24. For the six patients with early years GCA assessments at baseline and month 24, mean (SD) GCA scores decreased from 72.3 (21.3) at baseline to 62.7 (34.9) at month 24. School age GCA scores were stable over 2 years: mean (SD) 72.4 (11.8, n = 10) at baseline; 74.3 (12.3, n = 8) at month 24. Mean (SD) VABS-II Adaptive Behavior Composite (ABC) scores were stable throughout the study (baseline, 81.8 [11.8, n = 36]; month 24, 81.0 [10.2, n = 13]). Some associations between items and domains of HS-FOCUS (p < 0.05) and DAS-II GCA and VABS-II ABC scores were shown, but there was no clear pattern of changes in HS-FOCUS over 2 years. CONCLUSIONS: The DAS-II measured changes in cognitive function over 2 years in younger patients with MPS II, whereas cognitive function in older patients remained stable. Further research is required to confirm the content validity of the DAS-II in different patient populations with MPS II. The VABS-II and HS-FOCUS were not sensitive tools for measuring behavioral and functional changes over 2 years. These findings may inform selection of appropriate cognitive and behavioral assessment tools for future studies.

A 5-Year Retrospective Assessment of Clinical Presentation Associated With Sports Injury in Young People Presenting to a Tertiary Eye Center.

PURPOSE: To examine the incidence and initial presentation of sports-related ocular injury in youth. METHODS: This retrospective case series study was performed at Massachusetts Eye and Ear, Boston, Massachusetts. Inclusion criteria were visit dates between January 1, 2010 and December 31, 2015, age 5 to 25 years, an ocular injury International Classifcation of Disease code, and a sports-related mechanism of injury. RESULTS: The final sample was 223 patients, representing approximately 20% of all youth eye injuries (mean age: 16.2 years (range: 6 to 24 years); 78.9% boys, 21.2% girls). The most common diagnosis was hyphema (72.2%). Most injuries occurred with soccer (23.3%), baseball (17.0%), and basketball (11.7%), with a mean visual acuity of 20/40, 20/50, and 20/50, respectively. The injuries with the lowest mean visual acuity resulted from paintball (20/500) and airsoft gun shooting (20/200). Thirty-three patients (14.7%) required surgical intervention. The average number of follow-up visits within 1 year was five. CONCLUSIONS: Approximately 20% of youth ocular injury visits were sports related, with male teenagers affected most. Hyphema was the most common type of sports-related eye injury posing a lifelong risk of ocular complications. Popular youth sports such as soccer, baseball, and basketball caused the most eye injuries. Shooting sports with paintball and airsoft guns were associated with the greatest loss of vision. Patients infrequently reported the use of protective eyewear at the time of injury. Protective eye equipment should be worn by youth participating in sports to prevent ocular trauma and the potential for surgical intervention. [J Pediatr Ophthalmol Strabismus. 2021;58(6):377-384.].

Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers.

BACKGROUND AND METHODS: Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A. Neurological involvement results in severe disability and premature death, but understanding of the natural history of the disease remains limited. In this study, 32 caregivers of patients with MLD in the USA (16 with late-infantile MLD; 16 with juvenile MLD) were interviewed about their experiences of the disease. Qualitative analysis of the interview transcripts was performed to gain insights into symptom onset, the diagnostic process and disease progression, with a focus on the differences between late-infantile and juvenile MLD. RESULTS: The mean ages of patients at interview were 7.6 years and 20.7 years for individuals with late-infantile and juvenile MLD, respectively. Patients with late-infantile MLD had a mean age of 1.5 years at symptom onset and 2.6 years at diagnosis. The most common initial symptoms in this group related to problems with gross motor function (12/16 patients); 11 patients never learned to walk independently. For patients with juvenile MLD, the mean ages at symptom onset and diagnosis were 8.7 years and 11.6 years, respectively. Cognitive or social/behavioural problems were the most common first reported symptoms in this group (9/16 and 7/16 patients, respectively); these were generally followed by deterioration in motor function. The rate of functional decline was more rapid in patients with late-infantile MLD than those with juvenile MLD; the mean time from first symptom to first functional loss was 1 year versus 6.1 years, respectively. Nine patients with juvenile MLD and three with late-infantile MLD had undergone a haematopoietic stem cell transplant; outcomes following transplant were variable. CONCLUSIONS: Our data highlight clear overall differences in symptom profiles and disease progression between late-infantile and juvenile MLD, but also indicate some degree of interindividual variability within each subtype. These findings are broadly consistent with previously published descriptions of MLD and enhance our knowledge of the natural history of the disease, which ultimately should help to improve patient care and aid assessments of the effectiveness of disease-related interventions in the future.

Assessing the impact on caregivers caring for patients with rare pediatric lysosomal storage diseases: development of the Caregiver Impact Questionnaire.

BACKGROUND: Capturing the impact of caring for patients with debilitating rare disease is important for understanding disease burden. We aimed to develop and validate an instrument to measure the impact on caregivers of caring for children with three lysosomal storage diseases (LSDs): metachromatic leukodystrophy (MLD), neuronopathic mucopolysaccharidosis type II (MPS II) and mucopolysaccharidosis type IIIA (MPS IIIA). METHODS: A draft instrument was developed based on targeted literature searches and revised through sequential qualitative interviews with caregivers of patients first with MLD (n = 16), then with MPS II (n = 22), and finally with MPS IIIA (n = 8). The instrument, which covered domains of physical, emotional, social and economic burden, was refined at each stage of development based on caregiver feedback. Saturation of major concepts was reached during concept elicitation (MLD and MPS II). RESULTS: It was confirmed that caring for a patient with an LSD impacts social functioning, emotional/psychological functioning, physical functioning, daily activities, and finances/work productivity. Results from cognitive debriefing of the draft questionnaires were considered during each round of interviews, resulting in a final set of items that caregivers found clear and easy to understand. The Caregiver Impact Questionnaire (CIQ) has 30 items in five domains: (1) social functioning (7 items); (2) impact on daily activities (5 items); (3) emotional/psychological functioning (10 items); (4) physical functioning (6 items); and (5) financial impact (2 items). CONCLUSIONS: These findings demonstrate that the content of the CIQ is relevant for determining the impact of caring on caregivers of patients with MLD, MPS II and MPS IIIA.

Validation of the shortened Perceived Medical Condition Self-Management Scale in patients with chronic disease.

Self-efficacy, or perceived competence, has been identified as an important factor in self-management behaviors and health outcomes in patients with chronic disease. Measures of self-management self-efficacy are currently available for multiple forms of chronic disease. One established measure is the 8-item Perceived Medical Condition Self-Management Scale (PMCSMS). This study investigated the use of the PMCSMS in samples of patients with a chronic disease to develop an abbreviated version of the scale that could be more readily used in clinical contexts or in large population health cohort studies. The PMCSMS was administered as either a generic scale or as a disease-specific scale. The results of analyses using item response theory and classical test theory methods indicated that using 4 items of the scale resulted in similar internal consistency (α = .70-0.90) and temporal stability (test-retest r = .75 after 2 to 4 weeks) to the 8-item PMCSMS (r = .81 after 2 to 4 weeks). The 4 items selected had the greatest discriminability among participants (α parameters = 2.49-3.47). Scores from both versions also demonstrated similar correlations with related constructs such as health literacy (r = .13-0.29 vs. 0.14-0.27), self-rated health (r = .17-0.48 vs. 0.26-0.50), social support (r = .21-0.32 vs. 0.25-0.34), and medication adherence (r = .20-0.24 vs. 0.20-0.25). The results of this study indicate that 4-item PMCSMS scores are equally valid but more efficient, and have the potential to be beneficial for both research and clinical applications. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Literature review to assemble the evidence for response scales used in patient-reported outcome measures.

BACKGROUND: In the development of patient-reported outcome (PRO) instruments, little documentation is provided on the justification of response scale selection. The selection of response scales is often based on the developers' preferences or therapeutic area conventions. The purpose of this literature review was to assemble evidence on the selection of response scale types, in PRO instruments. The literature search was conducted in EMBASE, MEDLINE, and PsycINFO databases. Secondary search was conducted on supplementary sources including reference lists of key articles, websites for major PRO-related working groups and consortia, and conference abstracts. Evidence on the selection of verbal rating scale (VRS), numeric rating scale (NRS), and visual analogue scale (VAS) was collated based on pre-determined categories pertinent to the development of PRO instruments: reliability, validity, and responsiveness of PRO instruments, select therapeutic areas, and optimal number of response scale options. RESULTS: A total of 6713 abstracts were reviewed; 186 full-text references included. There was a lack of consensus in the literature on the justification for response scale type based on the reliability, validity, and responsiveness of a PRO instrument. The type of response scale varied within the following therapeutic areas: asthma, cognition, depression, fatigue in rheumatoid arthritis, and oncology. The optimal number of response options depends on the construct, but quantitative evidence suggests that a 5-point or 6-point VRS was more informative and discriminative than fewer response options. CONCLUSIONS: The VRS, NRS, and VAS are acceptable response scale types in the development of PRO instruments. The empirical evidence on selection of response scales was inconsistent and, therefore, more empirical evidence needs to be generated. In the development of PRO instruments, it is important to consider the measurement properties and therapeutic area and provide justification for the selection of response scale type.

Patients' motivations and interest in research: characteristics of volunteers for patient-led projects on PatientsLikeMe.

PLAIN ENGLISH SUMMARY: PLM is an online platform that provides tools for individuals to track their health and connect with other patients and while PLM has invited patients to participate in various research projects throughout the years, an examination into what motivates patients to want to get involved in clinical research has not been done. During our analysis of applications submitted by members of the PLM community, we looked for reasons patients want to participate in research and their overall beliefs about clinical research, in general. In addition, we analyzed obstacles and barriers toward patients' research participation. We observed the following:Patients are typically motivated by their individual needs and are most interested in research specific to their own condition.To get the most from patients' involvement and to enhance patients' contribution towards research goals, researchers should explain the research goal and requirements of each goal in clear and transparent terms, making it easy for patients to understand, thus avoiding any potential miscommunication.Future studies are needed to determine the best methods for involving patients in clinical research. BACKGROUND: Historically, throughout the clinical and medical research arenas, patients have been perceived as passive "subjects" rather than as individuals who may have thoughts regarding research development, research plans, implementation of research studies, and data analysis. However, it is becoming more clear that patients increasingly want to have a more active role in clinical research studies and in the management of their own medical conditions as evidenced by a "no decision about us without us" stance, meaning patients want to make informed decisions about their health while working alongside their healthcare professionals. The central aim of this research study was to determine patients' motivations for being involved in research design and understand their perceptions of current research practices. METHODS: Two independent qualitative studies were conducted. In Study 1, we analyzed applications submitted by self-identified patients from within the PatientsLikeMe (PLM) community, for acceptance onto our advisory panel. The advisory panel was tasked with developing a best practice guide for how to involve patients in research. During the qualitative analysis, we identified major reasons for and topics of interest associated with PLM members' motivation to apply to the advisory panel. In Study 2, we analyzed applications from PLM community members and from patients outside the PLM community for a patient-led patient-reported-outcome (PRO) development project. Similar to Study 1, we identified themes associated with patients' motivations to participate in developing a new PRO. RESULTS: PLM members are interested in being involved in medical research for various reasons, including facilitating provider-patient communication, improving comprehension of medical information, understanding their disease, and bringing a more individualized approach to health care in general. CONCLUSION: Challenges in the process of appropriate involvement of patients in research are discussed. In both studies, the applicants shared their interests in being involved in research. However, in Study 2, many of the patients shared ideas that were not appropriate for the development of a PRO, which indicated limitations in how the invitation and application explained the project to patients. Future studies should contribute to determining the most appropriate method for involving patients in various settings.

Partnering with patients using social media to develop a hypertension management instrument.

Hypertension is a lifelong condition; thus, long-term adherence to lifestyle modification, self-monitoring, and medication regimens remains a challenge for patients. The aim of this study was to develop a patient-reported hypertension instrument that measured attitudes, lifestyle behaviors, adherence, and barriers to hypertension management using patient-reported outcome data. The study was conducted using the Open Research Exchange software platform created by PatientsLikeMe. A total of 360 participants completed the psychometric phase of the study; incomplete responses were obtained from 147 patients, and 150 patients opted out. Principal component analysis with orthogonal (varimax) rotation was executed on a data set with all completed responses (N = 249) and applied to 43 items. Based on the review of the factor solution, eigenvalues, and item loadings, 16 items were eliminated and model with 29 items was tested. The process was repeated two more times until final model with 14 items was established. In interpreting the rotated factor pattern, an item was said to load on any given component if the factor loading was ≥0.40 for that component and was <0.40 for the other. In addition to the newly generated instrument, demographic and self-reported clinical characteristics of the study participants such as the type of prescribed hypertension medications, frequency of blood pressure monitoring, and comorbid conditions were examined. The Open Research Exchange platform allowed for ongoing input from patients through each stage of the 14-item instrument development.

Typology of alcohol users based on longitudinal patterns of drinking.

OBJECTIVE: Worldwide, alcohol is the most commonly used psychoactive substance. However, heterogeneity among alcohol users has been widely recognized. This paper presents a typology of alcohol users based on an implementation of idiographic methodology to examine longitudinal daily and cyclic (weekly) patterns of alcohol use at the individual level. METHOD: A secondary data analysis was performed on the pre-intervention data from a large randomized control trial. A time series analysis was performed at the individual level, and a dynamic cluster analysis was employed to identify homogenous longitudinal patterns of drinking behavior at the group level. The analysis employed 180 daily observations of alcohol use in a sample of 177 alcohol users. RESULTS: The first order autocorrelations ranged from -.76 to .72, and seventh order autocorrelations ranged from -.27 to .79. Eight distinct profiles of alcohol users were identified, each characterized by a unique configuration of first and seventh autoregressive terms and longitudinal trajectories of alcohol use. External validity of the profiles confirmed the theoretical relevance of different patterns of alcohol use. Significant differences among the eight subtypes were found on gender, marital status, frequency of drug use, lifetime alcohol dependence, family history of alcohol use and the Short Index of Problems. CONCLUSIONS: Our findings demonstrate that individuals can have very different temporal patterns of drinking behavior. The daily and cyclic patterns of alcohol use may be important for designing tailored interventions for problem drinkers.

Prevention of smoking in Middle School Students: psychometric assessment of the Temptations to Try Smoking Scale.

Establishment of psychometrically sound measures is critical to the development of effective interventions. The current study examined the psychometric properties, including factorial invariance, of a six item Temptations to Try Smoking Scale on a sample of middle school students. The sample of 6th grade students (N=3527) was from 20 Rhode Island middle schools and was 52% male and 84% white. The Temptations to Try Smoking Scale consisted of two correlated subscales: Positive Social and Curiosity/Stress. Structural equation modeling was implemented to evaluate the factorial invariance across four different subgroups defined by gender (male/female), race (white/black), ethnicity (Hispanic/Non-Hispanic), and school size (<200/ >200 6th graders). A model is factorially invariant when the measurement model is the same in each of the subgroups. Three levels of invariance were examined in sequential order: 1) Configural Invariance (unconstrained nonzero factor loadings); 2) Pattern Identity Invariance (equal factor loadings); and 3) Strong Factorial Invariance (equal factor loadings and measurement errors). Strong Factorial Invariance provided a good fit to the model across gender (CFI=.96), race (CFI=.96), ethnicity (CFI=.94), and school size (CFI=.97). Coefficient Alphas for the two subscales, Positive Social and Curiosity/Stress, were .87 and .86, respectively. These findings provide empirical support for the construct validity of the Temptations to Try Smoking Scale in middle school students.

Identifying subtypes of dual alcohol and marijuana users: a methodological approach using cluster analysis.

Alcohol is the most common psychoactive substance used with marijuana. However, little is known about the potential impact of different levels of use of both alcohol and marijuana and their influence on risky behaviors, injuries and psychosocial functioning. A systematic approach to identifying patterns of alcohol and marijuana use associated with increased risks has not yet been identified in the literature. We report on the secondary analysis of data collected from a RCT conducted in a busy urban emergency department. Cluster analysis was performed on the patterns of past 30-day alcohol and marijuana use in two random subsamples N1=210 and N2=217. Four distinct subtypes of those who use both alcohol and marijuana were identified: (1) Daily Marijuana and Weekly Alcohol users; (2) Weekly Alcohol and Weekly Marijuana users; (3) Daily Alcohol and Daily Marijuana users; and (4) Daily Alcohol, Weekly Marijuana users. The four subtypes were replicated in both subsamples and examination of the external validity using ANOVA to determine cluster differences on psychosocial and behavioral variables confirmed the theoretical relevance of different patterns of alcohol and marijuana use. There were significantly different psychosocial negative consequences and related risky behaviors among subtypes. We found that Daily Alcohol and Daily Marijuana users are at the highest risk to experience more negative consequences and engage in a broader spectrum of risky behaviors related to both substances, than the other three types of alcohol and marijuana users.

Collaborative behavioral management among parolees: drug use, crime and re-arrest in the Step'n Out randomized trial.

AIMS: To determine whether collaborative behavioral management (CBM) reduces substance use, crime and re-arrest among drug-involved parolees. DESIGN: Step'n Out was a randomized behavioral trial of CBM versus standard parole (SP) during 2004-08. CBM adapted evidence-based role induction, behavioral contracting and contingent reinforcement to provide parole officer/treatment counselor dyads with positive tools in addition to sanctions to manage parolees' behavior over 12 weeks. SETTING: Six parole offices in five states in the USA. PARTICIPANTS: Parolee volunteers with a mandate for addiction treatment and a minimum of 3 months of parole (n = 476). Follow-up was 94% at 3 months and 86% at 9 months. MEASUREMENTS: Drug use and crime in a given month from calendar interviews 3 and 9 months after parole initiation, and re-arrests from criminal justice administrative data. FINDINGS: The CBM group had fewer months in which they used their primary drug [adjusted risk ratio (ARR) 0.20, 95% confidence interval (CI): 0.05, 0.78, P = 0.02] and alcohol (ARR 0.38, 95% CI: 0.22, 0.66, P = 0.006) over follow-up. CBM had its greatest effects among parolees who reported marijuana or another 'non-hard' drug as their primary drug; parolees who preferred stimulants or opiates did not benefit. No differences were seen in total crime, re-arrests or parole revocations. CONCLUSIONS: Collaborative behavioral management may reduce substance use among primary marijuana or other 'non-hard' drug-using parolees without increasing revocations. Because the majority of drug violation arrests in the United States are for marijuana, these findings have important implications for the management of a substantial proportion of the US community correctional population.