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Introduction: The Alzheimer's Disease Composite Score (ADCOMS) is a tool developed to detect clinical progression and measure treatment effect in patients in early stages of Alzheimer's disease (AD). The psychometric properties of the ADCOMS have been established; however, the threshold for clinical meaningfulness has yet to be identified. Methods: Anchor-based, distribution-based, and ROC curve analyses were used to estimate clinically meaningful thresholds for change in ADCOMS for patients with mild cognitive impairment (MCI) and AD dementia. This study included data from three sources: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the National Alzheimer's Coordinating Center (NACC), and a legacy dataset that included data from four sources: the placebo group from three MCI trials and an earlier data cut from ADNI. Results were stratified by disease severity (MCI vs. dementia) and APOE ε4 carrier status. Results: A total of 5355 participants were included in the analysis. The ADCOMS was able to detect change for MCI and dementia patients who experienced a meaningful decline in cognition (as defined by the Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB]) between baseline and month 12. The following ADCOMS cut-offs were proposed: 0.05 for MCI and 0.10 for dementia. Conclusions: The ADCOMS was previously established as a valid and reliable tool for use in clinical trials for MCI due to AD and dementia populations. By defining thresholds for clinically meaningful change of ADCOMS, this work is an important step in interpreting clinical findings and estimates of treatment effects in early stage AD trials. [ABSTRACT FROM AUTHOR]

Background: It is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient's perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia. Methods: This is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating ("Shaky hands or arms," "Restlessness," and "Difficulty sleeping"), sedating ("Sleepy during the day", "Feeling drugged or like a zombie," and "Feeling dizzy/Fainted") or other side effects ("Problems enjoying sex" and "Gaining weight"), and additional questions related to impacts on function and quality of life were asked. Results: In total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14–70). The most prevalent side effects were "Sleepy during the day" (83.2%), "Difficulty sleeping" (74.7%), "Dry mouth" (63.9%), "Problems enjoying sex" (53.4%) and "Gaining weight" (52.4%). Women reported the side effects of "Sleepy during the day", "Problems enjoying sex" and "Gaining weight" more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients. Conclusion: Stable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Rapid onset of therapeutic action for antidepressant medication represents a major area of unmet medical need, and any such effects have been difficult to detect using standard study designs and measurement strategies. We conducted a randomized, open-label study with blinded raters using daily process assessment vs. standard weekly assessment to answer the following study questions: 1) is it possible to detect an antidepressant response more rapidly with daily assessment than with standard assessment approaches? 2) what is the burden of daily assessment on participants relative to standard clinical assessments? and 3) does the process of completing daily assessments have any effect on clinic-based assessments such as the Hamilton Depression Rating Scale (HAM-D)? Method: Seventy-eight outpatients with major depressive disorder who received open-label fluoxetine were randomized to standard weekly clinic assessment or standard weekly clinic assessment plus daily assessment, and were followed for 28 days. Data were collected between September, 2002 and August, 2003. Results: Daily assessment appeared to have no effect on 17-item HAM-D or MADRS scores obtained in the clinic. Survival analyses revealed that daily diaries detected therapeutic effects more quickly than did standard weekly clinic assessments, across most endpoints. Perceived burden of study participation was not significantly increased by daily diary completion, nor reflected in higher dropout rates. Conclusion: Daily process assessment improves the ability to detect an early antidepressant response. [Copyright &y& Elsevier]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

The Schwartz Outcomes Scale-10 (SOS-10) is a 10-item scale developed to measure the effectiveness of psychiatric treatments. Using standard methodology, we translated the scale into Czech and examined the psychometric properties of the Czech version. 207 in-patients admitted to Prague Psychiatric Center were included in the study. All patients completed the SOS at admission and discharge. The SOS-10 scale was also administered to 170 persons from the general population. Reliability, validity and sensitivity to treatment change of the Czech SOS-10 were analyzed. The Cronbach's alpha coefficient was 0.92. The item-total correlation coefficients varied from 0.56 to 0.82. The SOS-10 correlated well with condition-specific measures including depression (BDI) and anxiety (BAI) and a global self-rated symptom severity scale (CGI). The SOS-10 also had significant correlations with the Health, Basic needs, Relationship, and Leisure time domains of the Czech version of the Subjective Quality of Life Analysis (SQUALA-CZ). The scale discriminated well between patients and controls, with patients scoring significantly lower on all SOS items. The patient sample's admission and discharge scores were significantly different, indicating that the scale is sensitive to treatment changes. We concluded that the Czech SOS-10 is valid with reliability and factor structure similar to the American language version. [ABSTRACT FROM AUTHOR]

The article reflects on the measurement and satisfaction of treatment satisfaction. It suggests that a strong theoretical understanding of the construct of treatment satisfaction is important because it will help to generate new ideas for research, and help regulators and researchers to evaluate empirical results in the area.

ABSTRACT Background and objectives: Although it is accepted that reflux of stomach acid causes gastroesophageal reflux disease (GERD), it is less well understood that it also contributes to the clinical signs and symptoms of laryngitis in the form of laryngopharyngeal reflux (LPR). Study objectives were to identify what is known about the impact of LPR on health-related quality of life (HRQL) compared with the impact of GERD on HRQL and to assess whether currently available HRQL instruments adequately measure this impact or if a new disease-specific instrument should be recommended. Methods: The authors combined a systematic literature review with prospective patient evaluation via focus groups. The review, using MEDLINE, focused on clinical characteristics and HRQL measurement and impact. Focus groups involving a total of 30 patients with LPR provided input on clinical manifestations of the disease and its HRQL impact. Results: Information gleaned from the literature indicates that less than 40% of patients presenting with symptoms of laryngitis directly attributable to reflux also report experiencing the classic symptoms of heartburn and acid regurgitation associated with GERD. Reflux laryngitis is thus a distinct clinical entity from GERD and may have a unique impact on HRQL. Although multiple instruments are available to assess the impact of GERD on HRQL, no specific instruments are available for LPR. Focus group discussions identified voice problems, chronic cough, throat clearing, and swallowing difficulties to be key concerns of patients with LPR. These manifestations negatively impact HRQL as described by the focus group participants, notably in role functioning, physical well-being, and emotional well-being. Conclusions: A disease-specific instrument to assess the impact of LPR on HRQL would contribute to clinical care and the evaluation of new therapies. This instrument would ideally be sensitive to the variety of LPR's symptomatic presentations. [ABSTRACT FROM AUTHOR]

Objectives: Treatments for acromegaly, a growth hormone disorder, can be burdensome to patients, often requiring multiple self-administered injections daily. We developed the Impact on Lifestyle Questionnaire (ILQ) to measure the impact on patient's lifestyle imposed by the burden of injectable treatments for acromegaly. The primary objective of this study was to establish the reliability and validity of the ILQ. Methods: The ILQ consists of the SF-12 and 30 additional questions. Thirty-four patients, from two sites, completed the ILQ and scales measuring related concepts. Fourteen patients also completed a retest survey 4 weeks later. Survey sample data were combined with ILQ data from another 56 patients with acromegaly for a factor analysis. Reliability was assessed with Cronbach's α and test-retest. Zero-order correlations were examined between ILQ subscales and symptoms, depression, SF-12 mental and physical components, a measure of self-care burden, appraisal of illness, and single-item measures of quality of life and satisfaction. Results: The preconceived subscale structure was supported by factor analysis. These factors were internally consistent and stable over time. Good convergent validity was demonstrated between the Burden and Disruption scales with other measures of the burden of treatment. Patients indicated that they were generally compliant with therapy, and that treatment was not particularly burdensome or disruptive. Results based on the ILQ were consistent with other scales and qualitative responses. Conclusions: The ILQ has three subscales, Burden, Lifestyle Disruption, and Compliance, that are reliable and demonstrate preliminary evidence of construct validity. [ABSTRACT FROM AUTHOR]

Objective: Tolerability and safety of treatments are important in oncology trials and should be informed by patient assessments. We identified the most relevant patient‐reported symptomatic adverse events (AEs) to measure in patients with non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Methods: This study selected relevant symptomatic AEs from 78 AEs available in the Patient‐Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) measurement system. Initially, symptomatic AEs were selected based on literature and product labeling reviews, and then core sets of symptomatic AEs were identified by patient and clinician interviews. Qualitative and descriptive analyses were performed using the data collected from three iterative rounds of patient interviews. Results: During concept elicitation interviews involving 29 patients, 12 symptomatic AEs were identified and were then adapted into a 25‐item PRO‐CTCAE form for use in future clinical trials along with commonly used PRO measures. Cognitive interviews showed that the PRO‐CTCAE items were easy to answer and appropriate for assessing the patients' experience with symptomatic AEs. This study also assessed disease symptoms, impacts, and overall patient experience. Conclusions: The 25‐item PRO‐CTCAE form captures the most relevant symptomatic AEs in this patient population, and it is available for future studies. Baseline characterization of AEs associated with this distinct patient group contributes to our broader knowledge about NSCLC and through platforms like Project Patient Voice will expand our understanding of treatment tolerability and safety for NSCLC. Ultimately, this data collection will help inform decision‐making for patients, caregivers, healthcare providers, and regulators. [ABSTRACT FROM AUTHOR]

Background: The total burden of migraine includes not only the episodes with headache pain but extends throughout the interictal periods. Interictal symptoms and associated psychological responses may profoundly impact well-being and drive treatment-seeking behavior. Methods: A cross-sectional online survey was conducted with participants aged ≥ 18 years, 250 with episodic migraine (EM) and 250 with chronic migraine (CM), having ≥ 4 monthly migraine headache days. All were naïve to galcanezumab or began ≤ 6 months before survey completion. The study evaluated factors associated with the Migraine Interictal Burden Scale (MIBS-4), including social determinants of health and well-being. Multiple linear regression, logistic regression, and random forests (RF) were used to explore predictors of MIBS-4. Results: The majority of participants (90%) were female with a mean (standard deviation) age of 40.6 (± 12.0) years and 18.1 (± 12.7) years since the first migraine episode. Sociodemographically, the EM and CM groups were similar. Common comorbidities were anxiety disorder (45%) and depression (44%). Migraine family history was reported in 59% of participants. MIBS-4 was correlated with a number of diverse variables, including well-being, anxiety sensitivity, income, aura symptoms, and the worst migraine pain in the year before starting galcanezumab. Linear and logistic regression identified years since the first symptom, worst migraine attack pain, premonitory symptoms, and income as significant predictors. RF explained more of the variance than multiple linear regression and introduced additional concepts to the prediction of MIBS, identifying well-being (WHO-5 total score), the WHO-5 item "cheerful and in good spirits," worry about exercise, and fear of missing social obligations as significant predictors. Socioeconomic status and income were also critical explanatory variables for interictal burden (IIB) based on regression modeling and RF. Still, income was the only variable significantly associated with IIB across regression and RF methods. Conclusions: Interictal burden should be considered in the medical care of people with migraine. This additional burden is holistic, with psychosocial and socioeconomic elements in addition to residual symptoms. It is essential to consider this when assessing the impact of IIB. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody). Methods: This is a cross-sectional, self-reported, online survey of subjects in Lilly's Emgality® Patient Support Program in 2022. Questionnaires collected insights into subjects' prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs. Results: Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2 years (± 11.9) at diagnosis and 40.6 (± 12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (± 4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects. Conclusion: People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey. Graphical abstract available for this article. [ABSTRACT FROM AUTHOR]

Focuses on a short scale designed to measure the effectiveness of mental health treatment across a wide range of mental health services and populations. Measurement of a broad domain of psychological health; Potential to be broadly responsive to a variety of treatment effects; Applications across psychiatric and psychological treatments and populations.

Presents a study which evaluated the effects of zidovudine therapy in patients with mildly symptomatic HIV infection. Background on HIV infection; Clinical characteristics of the patients; Data and methods used; Results and conclusions.

Presents an obituary for research scientist Aaron Antonovsky who died on July 7, 1994.

Background: Health‐related quality of life (HRQL) is an important goal for patients with major depressive disorder (MDD), but whether antidepressants improve HRQL in these patients is unclear. Here, we describe the real‐world effects of trazodone once‐a‐day (TzOAD) and selective serotonin reuptake inhibitor (SSRI) treatments on HRQL and functioning in adults with MDD. Methods: This 8‐week prospective, observational, open‐label, multicenter study was conducted in adults with moderate or severe MDD for whom TzOAD or SSRI were prescribed as monotherapy. The primary outcome was life enjoyment and satisfaction assessed via the patient‐reported Quality‐of‐Life Enjoyment and Satisfaction Questionnaire Short Form (Q‐LES‐Q‐SF) from baseline to week 8. Secondary outcomes included change in Q‐LES‐Q‐SF from baseline to weeks 1 and 2; severity of depressive symptoms using the Montgomery Åsberg Depression Rating Scale (MADRS) and sleep disturbance via the PROMIS SF‐SD 8b questionnaire at weeks 1, 2, and 8; and overall functioning via the Sheehan Disability Scale (SDS), hedonic capacity using the Snaith–Hamilton Pleasure Scale (SHAPS), and cognitive dysfunction using the Perceived Deficits Questionnaire (PDQ‐5) at baseline and week 8. Results: The study included 208 adults with MDD (mean [SD] age = 50.2 [14.3] years; 68.6% female; 98.4% White). Life enjoyment and satisfaction improved from baseline to week 8 for both treatment groups: Q‐LES‐Q‐SF mean (SD) scores were 27.5 (20.4) for the SSRI group and 39.0 (22.1) for the TzOAD group. Depressive symptoms and sleep disturbances also reduced from baseline to week 8: MADRS (SSRI, −15.7 [8.3]; TzOAD, −21.0 [9.8]); PROMIS SF‐SD 8b (SSRI, −9.9 [12.6]; TzOAD, −22.0 [12.6]). Mean change scores in Q‐LES‐Q‐SF, MADRS, and PROMIS SF‐SD 8b improved as early as week 1 in both groups. Mean scores also improved from baseline to week 8 on SDS (SSRI, −9.2 [7.4]; TzOAD, −14.3 [7.5]), SHAPS (SSRI, −6.6 [4.3]; TzOAD, −8.3 [4.4]), and PDQ‐5 (SSRI, −5.8 [4.5]; TzOAD, −7.7 [5.0]). Conclusions: In adults with MDD who received TzOAD or SSRIs, overall and individual HQRL domains improved rapidly and in parallel with improvements in depressive symptoms, with a slightly greater improvement observed in the TzOAD group. [ABSTRACT FROM AUTHOR]

Spasticity is common in multiple sclerosis (MS), often leading to functional limitations and disability. We developed a conceptual model of spasticity in MS integrating expert opinion, recent literature, and experiences of clinicians and people with MS spasticity. A conceptual model was developed based on a targeted literature review of articles published between 2014 and 2019, followed by input from clinicians, then input from participants with MS spasticity. Multidisciplinary experts on spasticity provided guidance at each step. Key concepts of the integrated spasticity conceptual model included: moderators; triggers; modifiers; treatment; objective manifestations; subjective experience; physical, functional, social, and emotional/psychological impacts; and long-term consequences. Participants with MS spasticity most frequently endorsed spasms, tightness, and pain as descriptors of spasticity. Some participants with MS spasticity had difficulty distinguishing spasticity from other MS symptoms (e.g. muscle weakness). Some triggers, emotional/psychological impacts, and long-term consequences of spasticity reported by participants with MS spasticity were not previously identified in the published literature. This conceptual model of spasticity, integrating published literature with the experience of clinicians, people with MS spasticity, and experts, demonstrates the complex, multidimensional nature of MS spasticity. This model may be used to improve clinician–patient dialogue, research, and patient care. Many people with multiple sclerosis (MS) have spasticity, generally in the lower limbs, but this symptom is complex and multidimensional and therefore difficult to characterize. MS spasticity may be influenced by moderators, triggers, modifiers, and treatment, all of which can affect objective measures and the subjective experience of spasticity. MS spasticity can have physical, functional, social, and emotional/psychological impacts as well as long-term consequences that can affect rehabilitation and ultimately reduce health-related quality of life for people with MS. Given that people with MS may view spasticity differently than their rehabilitation providers, providers should ask patients about their spasticity, including their moderators, triggers, modifiers, experience, impacts, long-term consequences, and effects on quality of life. This conceptual model provides a framework to improve clinician-patient dialogue, research, and rehabilitation for MS spasticity. [ABSTRACT FROM AUTHOR]

Comments on the ISPOR Task Force's report on translation and adaptation of patient outcomes measures by Wild et al. Consequences of relying on backward translation; Need for more empirical research on appropriate translation methodologies.

• Infertility diagnoses negatively affect patients and partners, men and women. • Emotional reactions point to significant cognitive threat appraisals • Diagnoses can trigger recollection of prior reproductive events or concerns • Natural language processing is an efficient text analysis tool in fertility care What are the emotional effects of infertility on patients, partners, or both, and how can qualitative thematic analyses and natural language processing (NLP) help evaluate textual data? A cross-sectional, multi-country survey conducted between March 2019 and May 2019. A total of 1944 patients, partners, or both, from nine countries responded to the open-ended question asking about their initial feelings related to an infertility diagnosis. A mixed-method approach that integrated NLP topic modelling and thematic analyses was used to analyse responses. Sentiment polarity was quantified for each response. Linear regression evaluated the association between patient characteristics and sentiment negativity. Common emotional reactions to infertility diagnoses were sadness, depression, stress, disappointment, anxiety, frustration, confusion and loss of self-confidence. NLP topic modelling found additional reactions, i.e. shared feelings with partners, recollections about causes of infertility and treatment experience. Responses to the open-ended question were brief (median: three words) with 71.8% conveying negative sentiments. Some respondent characteristics showed small but significant associations with sentiment negativity, i.e. country (Spain, China and France were more negative than the USA, P < 0.001, P < 0.003 and P < 0.009 respectively), treatment engagement (no treatment was more negative than one or more treatment, P = 0.027) and marital status (missing/other was more negative than divorced, P = 0.003). Infertility diagnoses create an emotional burden for patients and partners. The mixed-method approach provides a compelling synergy in support of the validity of these findings and shows potential for these techniques in future research. [ABSTRACT FROM AUTHOR]

Background: Zidovudine therapy is recommended for asymptomatic patients infected with the human immunodeficiency virus (HIV) who have fewer than 500 CD4+ cells per cubic millimeter. An analysis of the quality of life associated with therapy that integrated both the effects of adverse events and the benefits of delayed disease progression might influence this recommendation. Methods: We applied a survival analysis adjusted for the quality of life to data from a randomized trial conducted by the AIDS Clinical Trials Group. The trial compared treatment with 500 mg of zidovudine per day, 1500 mg of zidovudine per day, and placebo (Protocol 019) in 1338 asymptomatic HIV-infected patients. Results: The average time with neither a progression of disease nor an adverse event (symptom or laboratory finding) was 15.7, 15.6, and 14.8 months for patients receiving placebo, 500 mg of zidovudine, and 1500 mg of zidovudine, respectively. The incidence of severe symptoms was 13.8 percent in the placebo group, 15.2 percent in the 500-mg group, and 19.9 percent in the 1500-mg group (P = 0.038). After 18 months, the 500-mg group gained an average of 0.5 month without disease progression, as compared with the placebo group, but had severe adverse events an average of 0.6 month sooner. The 500-mg group had more quality-of-life-adjusted time than the placebo group only if the time lived after the progression of disease was considered by a patient to have less value than the time after the occurrence of a severe symptom. Conclusions: For asymptomatic patients treated with 500 mg of zidovudine, a reduction in the quality of life due to severe side effects of therapy approximately equals the increase in the quality of life associated with a delay in the progression of HIV disease. (N Engl J Med 1994;330:738-43.) [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic, life-threatening disease characterized by thrombosis, impaired bone marrow function, and complement-mediated hemolysis. The PEGASUS phase III clinical trial demonstrated superiority of pegcetacoplan over eculizumab regarding improvements in hemoglobin levels in patients with suboptimal response to prior eculizumab treatment. The objective of this post hoc analysis was to compare the patient-reported outcome (PRO) response rates observed among PEGASUS participants and the relationships between their PRO scores with clinical and hematological parameters. Data from the 16-week randomized, controlled (1:1 to pegcetacoplan or eculizumab) period of the PEGASUS trial included comparisons of weekly PRO measurements taken using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) scales. A clinically meaningful FACIT-F response was defined as an increase from baseline of ≥5 points. Convergent validity was assessed using conventional threshold correlations between FACIT-F, EORTC QLQ-C30, and laboratory parameters. A clinically meaningful improvement in FACIT-F score was seen in 72.2% of pegcetacoplan-treated patients compared to 22.9% of eculizumab-treated patients. At week 16, the FACIT-F total score correlated with hemoglobin levels (r=0.47, p< 0.0001), absolute reticulocyte count (r=-0.37, p<0.01), and indirect bilirubin levels (r=-0.25, p<0.05). Clinically meaningful improvements in pegcetacoplan-treated patients were also observed for multiple EORTC scales. Fatigue and other self-reported outcomes were correlated with clinically meaningful improvements in clinical and hematological parameters. Clinical trial registration: NCT03500549. [ABSTRACT FROM AUTHOR]

Presents a study on the behaviors of bisexually active men, who are defined as men having sex with a man and a woman, who were compared with men who had sex with men only. Reference to bisexual behaviors in men not being well understood; Methods used in the study; Details on bisexual men being identified as problem drinkers; Results of the study; Discussion on the study.

Purpose: The Autism Behavior Inventory (ABI) is an observer-reported outcome scale measuring core and associated features of autism spectrum disorder (ASD). Extensive scale development (reported elsewhere) took place, in alignment with the Food and Drug Administration's patient-reported outcome guidance, to address the need for instruments to measure change and severity of ASD symptoms.Methods: Cognitive interviewing was used to confirm understanding and content validity of the scale prior to its use in clinical trials. Respondents were caregivers of individuals with ASD (N = 50). Interviews used a hybrid of the "think-aloud" and verbal probing approach to assess ABI's content validity and participant understanding of the instrument, including: item clarity and relevance; item interpretation; appropriateness of response scales; and clarity of instructions. Audio-recordings of the interviews were transcribed for qualitative data analysis. The scale was revised based on participant feedback and tested in a second round of interviews (round 1 N = 38, round 2 N = 12).Results: In total, 67/70 items reached ≥ 90% understandability across participants. Caregivers were able to select an appropriate response from the options available and reported finding the examples helpful. Based on participant feedback, instructions were simplified, 8 items were removed, and 10 items were reworded. The final revised 62-item scale was presented in round 2, where caregivers reported readily understanding the instructions, response options, and 61/62 items reached ≥ 90% understandability.Conclusions: Cognitive interviews with caregivers of a diverse sample of individuals with ASD confirm the content validity and relevance of the ABI to assess core and associated symptoms of ASD. [ABSTRACT FROM AUTHOR]

BACKGROUND The Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported PCSS (PR-PCSS) are newly developed tools for assessing cellulite severity. OBJECTIVE To report on the reliability, validity, and ability to detect a change in cellulite severity on the buttocks of adult women with the CR-PCSS and PR-PCSS. MATERIALS AND METHODS Content validity of both scales was established through concept elicitation and cognitive interviews. Test-retest reliability was evaluated, and intra-rater (both scales) and inter-rater (CR-PCSS only) reliability were estimated using intraclass correlation coefficients (ICCs) for agreement and consistency. Ability to detect a change was determined using the Subject-Global Aesthetic Improvement Scale (GAIS) or Investigator-GAIS as anchors. RESULTS For the CR-PCSS (n = 6) at baseline and Day 2, the mean interrater ICCs were $0.70 and mean intrarater ICCs (95% confidence interval [CI]) were $0.81 (0.72-0.90) for both buttocks. For the PR-PCSS (n = 99) at baseline and Day 14, the mean test-retest reliability ICCs (95% CI) were $0.86 (0.79-0.91) for both buttocks. A clinically meaningful change was 1.0 point on the PR-PCSS and 1.0 on the CR-PCSS. CONCLUSION The CR-PCSS and PR-PCSS reliably assess cellulite severity of the buttocks and can detect a clinically meaningful change after treatment for cellulite. [ABSTRACT FROM AUTHOR]

Objective: Pantothenate kinase‐associated neurodegeneration (PKAN) is an autosomal‐recessive, neurodegenerative disorder with a mixed‐motor phenotype caused by a defective PanK2 enzyme, for which there are few adequate treatment options. Clinimetrically sound measures of patient‐reported outcomes are necessary to facilitate therapeutic development for this debilitating disease. This study's objective was to develop such a scale and assess its clinimetric properties. Methods: A conceptually driven, iterative, content development process incorporating input from experts, caregivers, and patients was used. Scale items were initially adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) Part II resulting in the 12‐item Pantothenate Kinase‐Associated Neurodegeneration Activities of Daily Living (PKAN‐ADL). The PKAN‐ADL scale was administered to caregivers (n = 37) and patients (n = 2) twice over 2 weeks, along with selected Quality of Life in Neurological Disorders (Neuro‐QoL) measures, selected attributes of the Health Utilities Index (HUI)‐2/3, and the Stroke Aphasia Depression Questionnaire (SADQ‐10) to assess construct validity. Results: Internal consistency was 0.93, with excellent test‐retest reliability (intraclass correlation coefficient = 0.99). Of the 12 items, 25% (n = 3) showed a ceiling effect >30% (range, 31–54) and 42% (n = 5) showed a floor effect >30% (range, 31–46), reflecting disease heterogeneity. Convergent validity was shown with Neuro‐QoL measures (rs > 0.90) and HUI‐2/3 attributes (rs ≥ 0.48); divergent validity was demonstrated with the SADQ‐10 (r = 0.11). Participants reported a high level of comprehension (98%), and average item relevance ratings (0–10 scale) ranged from 7.0 to 9.9. Conclusion: The PKAN‐ADL scale demonstrated acceptable content validity, with evidence of construct validity and excellent reliability. Overall results support the use of the PKAN‐ADL scale in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Transthyretin amyloidosis (ATTR amyloidosis), whether manifesting as familial amyloid polyneuropathy (ATTR-PN) or cardiomyopathy (ATTR-CM), is a progressive, debilitating, and often fatal, rare disease requiring significant caregiver support. This study aims to better characterize the burden of disease for ATTR amyloidosis patients and caregivers.Methods: Patients and caregivers in the USA and Spain were recruited through patient advocacy groups to complete a cross-sectional survey. Assessments included the 12-Item Short Form Health Survey, the Work Productivity and Activity Impairment Questionnaire, the Zarit Burden Interview, pain and symptom measures, health care resource use measures, and caregiving burden measures.Results: Respondents included 60 ATTR amyloidosis patients and 32 caregivers. Patients registered scores up to two standard deviations below normal for physical health, impairment in quality of life, and reduced work productivity. Patients with liver transplant versus without liver transplant reported better overall outcomes, and those without liver transplant reported a greater impact on physical versus mental health. A high rate of health care utilization in the 3 months prior to the survey was reported by patients. Caregivers reported substantial burden, including poor mental health, work impairment, and much time spent providing care (mean 45.9 h/week). Work productivity was impacted for employed patients and caregivers.Conclusion: ATTR amyloidosis was associated with high levels of impairment in many domains, including physical health, quality of life, and reduced productivity. Providing care for ATTR amyloidosis patients is associated with a negative impact on the mental health of caregivers. These results highlight the substantial burden of ATTR amyloidosis for patients and caregivers.Trial Registration: ClinicalTrials.gov: NCT01604122.Funding: Pfizer. [ABSTRACT FROM AUTHOR]

Objective:The objective of this study was to evaluate the validity of the Heartburn Reflux Dyspepsia Questionnaire (HRDQ), a newly developed measure of gastro-oesophageal reflux disease (GORD) symptoms. Specifically, the HRDQ was developed for patients, who still experience symptoms with proton pump inhibitor (PPI) treatment. Material and methods:The psychometric properties of HRDQ were evaluated based on data from two clinical trials of patients with GORD with a partial response to PPIs, one from the UK and one from Denmark and Germany. Results:The HRDQ had good internal consistency (Cronbach’s alpha range .83–.88) and test–retest reliability (intraclass correlation coefficient range .71–.90). Convergent and discriminant validity were supported by high correlations with ReQuest™ and ability to differentiate between groups based on ReQuest™ cut-off values. Responsiveness of HRDQ was demonstrated by moderate to high correlations with ReQuest™ change scores and time with symptoms. An HRDQ cut-off value of 0.70 for definition of ‘bad day’ was also evaluated. Conclusions:Based on existing evidence, the HRDQ is a valid and reliable measure of GORD symptoms that can be used as a study outcome in clinical trials. [ABSTRACT FROM PUBLISHER]

In 2014, the European Medicines Agency (EMA) released for comment a draft reflection paper on the use of patient-reported outcome (PRO) measures in oncology studies. A twelve-member International Society for Quality of Life Research (ISOQOL) taskforce was convened to coordinate the ISOQOL response. Twenty-one ISOQOL members provided detailed comments and suggestions on the paper: 81 % from academia and 19 % from industry. Taskforce members consolidated and further refined these comments and shared the recommendations with the wider ISOQOL membership. A final response was submitted to the EMA in November 2014. The impending publication of the EMA reflection paper presents a valuable opportunity for ISOQOL to comment on the current direction of EMA PRO guidance and strategy. The EMA paper, although focused on cancer, could serve as a model for using PROs in other conditions, as it provides a useful update surrounding some of the design issues common to all trial research including PRO endpoints. However, we believe there are a number of additional areas in need of greater consideration. The purpose of this commentary is therefore to highlight the strengths of this timely and potentially useful document, but also to outline areas that may warrant further discussion. [ABSTRACT FROM AUTHOR]

Purpose: An essential aspect of patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) is the integration of patient perspectives and experiences with clinical data to evaluate interventions. Thus, PCOR and CER require capturing patient-reported outcome (PRO) data appropriately to inform research, healthcare delivery, and policy. This initiative’s goal was to identify minimum standards for the design and selection of a PRO measure for use in PCOR and CER. Methods: We performed a literature review to find existing guidelines for the selection of PRO measures. We also conducted an online survey of the International Society for Quality of Life Research (ISOQOL) membership to solicit input on PRO standards. A standard was designated as “recommended” when >50 % respondents endorsed it as “required as a minimum standard.” Results: The literature review identified 387 articles. Survey response rate was 120 of 506 ISOQOL members. The respondents had an average of 15 years experience in PRO research, and 89 % felt competent or very competent providing feedback. Final recommendations for PRO measure standards included: documentation of the conceptual and measurement model; evidence for reliability, validity (content validity, construct validity, responsiveness); interpretability of scores; quality translation, and acceptable patient and investigator burden. Conclusion: The development of these minimum measurement standards is intended to promote the appropriate use of PRO measures to inform PCOR and CER, which in turn can improve the effectiveness and efficiency of healthcare delivery. A next step is to expand these minimum standards to identify best practices for selecting decision-relevant PRO measures. [ABSTRACT FROM AUTHOR]

Background: Valid, reliable biomarkers of depression severity and treatment response would provide new targets for clinical research. Noticeable differences in speech production between depressed and nondepressed patients have been suggested as a potential biomarker. Methods: One hundred five adults with major depression were recruited into a 4-week, randomized, double-blind, placebo-controlled research methodology study. An exploratory objective of the study was to evaluate the generalizability and repeatability of prior study results indicating vocal acoustic properties in speech may serve as biomarkers for depression severity and response to treatment. Speech samples, collected at baseline and study end point using an automated telephone system, were analyzed as a function of clinician-rated and patient-reported measures of depression severity and treatment response. Results: Regression models of speech pattern changes associated with clinical outcomes in a prior study were found to be reliable and significant predictors of outcome in the current study, despite differences in the methodological design and implementation of the two studies. Results of the current study replicate and support findings from the prior study. Clinical changes in depressive symptoms among patients responding to the treatments provided also reflected significant differences in speech production patterns. Depressed patients who did not improve clinically showed smaller vocal acoustic changes and/or changes that were directionally opposite to treatment responders. Conclusions: This study supports the feasibility and validity of obtaining clinically important, biologically based vocal acoustic measures of depression severity and treatment response using an automated telephone system. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcomes (PROs) are the consequences of disease and/or its treatment as reported by the patient. The importance of PRO measures in clinical trials for new drugs, biological agents, and devices was underscored by the release of the US Food and Drug Administration's draft guidance for industry titled “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims.” The intent of the guidance was to describe how the FDA will evaluate the appropriateness and adequacy of PRO measures used as effectiveness end points in clinical trials... [ABSTRACT FROM AUTHOR]

Background Most US studies that estimate EQ-5D index score generally apply the UK preference weights. We compared the validity of a newly-developed US weights to the UK weights for use of EQ-5D as a measure of health-related quality of life. Methods Data were collected from a randomized clinical trial for patients with HIV ( n = 1,126) in the US. Convergent validity was examined by comparing Pearson correlations of EQ-5D index scores with the MOS-HIV Health Survey scale scores and Physical and Mental Health Summary (PHS, MHS) scores using the US and UK weights. Known-groups validity of EQ-5D US versus UK index scores was compared using clinical variables (CD4+ cell count and HIV viral load), and the MOS-HIV PHS and MHS. Score changes in the EQ-5D index from baseline to week 50 were examined using effect size (ES) estimates. Results The mean EQ-5D index scores was slightly higher using US weights than UK weights (0.87 vs. 0.84, respectively). The correlation coefficient for EQ-5D utilities using the US and UK weights was 0.98. The correlations of EQ-5D index scores with the MOS-HIV scores were moderate and similar using the US and UK weights. The EQ-5D index scores discriminated equally well for both versions between levels of CD4+ count, HIV viral load, and PHS and MHS scores ( P < 0.05), suggesting equivalent known-groups validity. The changes in EQ-5D index scores from baseline to week 50 were similar for both versions (ES: 0.21 vs. 0.22 for US and UK, respectively), suggesting equivalent responsiveness to score changes. Conclusions EQ-5D index scores generated using UK and US preference weights showed equivalent psychometric properties. For assessing treatment benefit in a single population, the use of either the UK or US weights as a measure of HRQOL will not change inferences. However, for comparisons across US and UK populations, the choice between these two weights should be based on their relevance to the study population. [ABSTRACT FROM AUTHOR]

Patient reported outcomes provide the patient's perspective on the effectiveness of treatment. The draft Food and Drug Administration guidance on patient reported outcomes for labeling and promotional claims raises a number of method and measurement issues that require further clarification, including methods of determining responsiveness and minimal important differences. For clinical trials, instruments need to be based on a clear conceptual framework, have evidence supporting content validity and acceptable psychometric qualities. The measures must also have evidence documenting responsiveness and interpretation guidelines (i.e., minimal important difference) to be most useful as effectiveness endpoints in clinical trials. The recommended approach is to estimate the minimal important difference based on several anchor-based methods, with relevant clinical or patient-based indicators, and to examine various distribution-based estimates (i.e., effect size, standardized response mean, standard error of measurement) as supportive information, and then to triangulate on a single value or small range of values for the MID. Confidence in a specific MID value evolves over time and is confirmed by additional research evidence, including clinical trial experience. The MID may vary by population and context, and no one MID will be valid for all study applications involving a PRO instrument. Responsiveness and MID must be demonstrated and documented for the particular study population, and these measurement characteristics are needed for PRO labeling and promotional claims. [ABSTRACT FROM AUTHOR]

Identifies situational and partner characteristics associated with unprotected sex among women at risk for HIV infection in the U.S. Analysis of paired odds ratios and confidence intervals; Difference between unprotected and protected sexual encounters; Use of conditional logistic regression.

Presents a study which evaluated the relation between drinking, drug use and unprotected anal intercourse in young men who have sex with men only. Details on efforts to promote behavioral change to reduce human immunodeficiency syndrome (HIV) transmission; Methods used in the study; Information on the characteristics of men whose unsafe behavior increases after drinking; Results of the study; Discussion on the study.

Background: Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegenerative disorder with brain iron accumulation (NBIA).Objectives: To assess PKAN diagnostic pathway, history, and burden across the spectrum of PKAN severity from patient and/or caregiver perspectives.Methods: Caregivers of patients (n = 37) and patients themselves (n = 2) were interviewed in a validation study of the PKAN-Activities of Daily Living (ADL) scale. The current study used quartiles of the PKAN-ADL total score to divide patients by severity of impairment (Lowest, Second Lowest, Third Lowest, Highest). Diagnostic and treatment history, healthcare utilization, disease burden, and caregiver experience were compared between groups.Results: The analyses included data from 39 patients. Mean age at PKAN symptom onset (P = 0.0007), initial MRI (P = 0.0150), and genetic testing (P = 0.0016) generally decreased across the PKAN severity spectrum. The mean duration of illness did not differ among PKAN severity groups (range, 9.7-15.2 years; P = 0.3029). First MRI led to diagnosis in 56.4% of patients (range, 30.0-90.0%). A mean (SD) of 13.0 (13.1) medical and 55.2 (78.5) therapy visits (eg, physical, speech) occurred in the past year. More patients in the higher PKAN severity groups experienced multiple current functional losses and/or earlier onset of problems (P-values < 0.0500). Over half (56.8%) of caregivers experienced a change in employment because of caregiving. The percentage of patients requiring full-time caregiving increased across the PKAN severity spectrum (range, 11.1-100%; P = 0.0021).Conclusions: PKAN diagnosis was often delayed, most probably due to low awareness. Considerable burden of functional impairment and high healthcare utilization were found across the PKAN severity spectrum. [ABSTRACT FROM AUTHOR]