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We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92–0.94) and the Lung Cancer Symptom Scale-Mesothelioma (0.79–0.87) at each co-administration of the scales. The CSS also had good sensitivity to worsening disease and global quality-of-life ratings. The MDASI-MPM CSS can be used as an outcome in MPM clinical trials, including in responder analyses and at the individual patient level. It is brief enough to administer frequently, including electronically, to better capture symptom trajectories during and after a trial and in clinical practice. As a single score, the CSS addresses multiplicity issues that can arise when several symptoms increase due to worsening disease. Our process can be adapted to produce a CSS for other advanced-cancer trials.

Background Symptom assessment requires psychometrically validated questionnaires that are easy to use, relevant to the disease, and quick to administer. The MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM) was adapted from the general (core) MDASI to assess the severity of cancer-related and treatment-related symptoms specific to patients with this condition. The MDASI-MPM includes the 13 core MDASI symptoms, which are experienced by most cancer patients, and 6 MPM-specific items developed via qualitative interviewing, a method favored by the US Food and Drug Administration for instrument item generation and development. Qualitative interviewing that summarizes the item generation and development for the MDASI-MPM is detailed in a separate report. The psychometric study reported here was the next step in developing the validation dossier for the MDASI-MPM. Results In this secondary analysis of data from a Phase II trial, 248 patients provided MDASI-MPM data at multiple timepoints during therapy. Over time, fatigue, pain, shortness of breath, feeling of malaise, and muscle weakness were consistently the worst symptoms reported; symptoms interfered most with work and general activity and least with relations with others. Cronbach coefficient alpha values for all MDASI-MPM subscales were at least 0.88 at baseline and 0.91 during treatment, indicating good internal consistency reliability. Intraclass correlations of at least 0.86 for all MDASI-MPM subscales administered a cycle apart ( n  = 82) were indicative of good test-retest reliability. Correlations between MDASI-MPM subscales and LCSS-Meso scores were at least 0.70 ( P  < 0.001 for all comparisons). Patients with good performance status had significantly lower scores than did patients with poor performance status (all P  < 0.05), supporting evidence for known-group validity and sensitivity. Effect-size differences were 0.69 and higher, indicating medium-to-large effects. The minimally important difference in the MDASI-MPM subscales ranged from 1.0 to 1.5 points on a 0–10 scale. Conclusions Symptoms specific to a particular cancer, treatment method, or treatment site can be added to the core MDASI to create a tailored, “fit for purpose” instrument. We found the MDASI-MPM to be a valid, reliable, and responsive (sensitive) instrument for assessing the severity of symptoms of patients with MPM and their interference in patients’ daily functioning.

Characterize follicular lymphoma (FL) treatment patterns among elderly patients using a dataset with longer follow-up time. Using the linked Surveillance, Epidemiology and End Results-Medicare data, we identified patients diagnosed with FL between 2000 and 2013 with claims data until 2014. We investigated the treatments received and assigned them to lines of treatment. We identified 10,238 elderly patients. Over a 4.7-year median follow-up, 78% of the patients received at least first-line treatment. Fewer individuals received second-line (47%) and third-line (30%) treatments. RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), RCVP (rituximab, cyclophosphamide, vincristine and prednisolone) and rituximab monotherapy were the most common treatment regimens. One in five elderly patients did not receive FL-directed therapy. The most common treatment regimens were limited to RCHOP, RCVP and rituximab monotherapy.

Purpose Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung pleura. The MD Anderson Symptom Inventory (MDASI) is a patient-reported outcome (PRO) measure of symptom burden, the combined impact of disease-related and treatment-related symptoms on functioning. Validated PRO measures may require modification for use in specific study populations. We sought to modify the MDASI for patients with MPM and create a fit-for-purpose symptom-burden measure for use in a clinical trial, according to US Food and Drug Administration guidance on PRO utilization to support labeling claims. Methods A literature review for MPM symptoms was conducted. Patients with MPM were qualitatively interviewed about experiences of disease and treatment. Descriptive analysis identified symptoms and interference with functioning to define MPM-related symptom burden. An expert panel rated the relevance of identified symptoms to patients with MPM. Patients who received the investigational drug in a previous Phase I study were interviewed for drug-specific symptoms. Results Literature review and interviews of 20 patients identified 31 MPM-related symptoms. A conceptual model of MPM-related symptom burden was developed. After expert-panel relevance review, five MPM-specific items and the 13 core MDASI symptoms met criteria for inclusion in a provisional MDASI-MPM for psychometric testing. Interviews with six patients identified six drug-specific symptoms; three were mentioned by multiple patients. Of these three, one was not in the core MDASI. Conclusions The MDASI-MPM has established content validity and, with the addition of one symptom item, is ready for psychometric testing as fit-for-purpose for a clinical trial of an investigational agent.

ABSTRACT Objective: Antibiotics are clinically indicated for acute bacterial rhinosinusitis, but they may be prescribed inappropriately. This retrospective study examined how labeled recommendations for duration of moxifloxacin and levofloxacin treatment of acute bacterial rhinosinusitis compare with real-world practice, and compared the failure and recurrence rates, and associated charges. Methods and main outcome measures: The PharMetrics Patient-Centric claims database was searched over a 3‐year period for episodes of acute rhinosinusitis treated within 5 days with moxifloxacin or levofloxacin. The duration of antibiotic treatment prescribed was compared with the labeled recommendation. Failure rates (a second antibiotic claim to treat acute rhinosinusitis within 30 days of the first claim), recurrence rates (subsequent antibiotic claims to treat any rhinosinusitis more than 30 days after the original or second [in the case of failure] claim), and treatment charges from the perspective of the payer (health insurer) were also compared using multivariate analysis. Results: The initial duration prescribed of moxifloxacin was shorter than for levofloxacin (–1.65 days, p < 0.0001), reflecting the shorter labeled recommendation (10 days versus 10–14 days). The durations of monotherapy (–2.06 days, p < 0.0001) and of all antibiotic treatment (–1.97 days, p < 0.0001) were also significantly shorter for episodes treated initially with moxifloxacin. The odds ratio for treatment failure (0.718; 95% confidence interval = 0.598–0.863; p = 0.0004) and the hazard ratio for recurrence (0.652; p = 0.0005) were both significantly lower for moxifloxacin than for levofloxacin, and resulted in lower total treatment charges (–$37.94 ± 13.65; p = 0.0055). Conclusion: The shorter treatment durations seen for moxifloxacin in this database of real-world care reflect the label-recommended duration for acute rhinosinusitis. Despite this shorter duration of therapy, moxifloxacin resulted in better outcomes than levofloxacin in terms of the risk of treatment failure and recurrence. In addition, the total charges were lower for patients treated with moxifloxacin.

A better understanding of how antimicrobial therapies affect the total cost of lower uncomplicated urinary tract infection, including direct (e.g., doctor visits), indirect (e.g., productivity) and intangible (e.g., pain) costs would facilitate selection of an optimal therapeutic approach. The results of this literature review indicate that the there is a considerable societal burden from uncomplicated urinary tract infection, with approximately US$1 billion in indirect and over $600 million in direct costs in 1995. However, no single identified study incorporated all three cost components, there are gaps in the knowledge concerning the current extent of these costs, and there are no comparative assessments based on total cost. Research is needed to provide current insights on the burden of uncomplicated urinary tract infection in terms of direct, indirect and intangible costs.

We evaluated the effectiveness of an educational brochure designed to increase patient knowledge about uncomplicated urinary tract infections (uUTIs). Participants were adult female outpatients (average age, 45 years) with a clinical diagnosis of uUTI. The 1,972 study sites (primary care physicians' offices and urology clinics) were randomized to receive patient enrollment kits with or without educational brochures. Pre- and post-treatment uUTI knowledge was assessed by questionnaire in 6,922 women who either received an educational brochure (n=3,431) or did not (n=3,491). Among those who received a brochure, the mean uUTI knowledge score increased by 0.59 from pre- to post-test. In contrast, the mean score of those who did not receive a brochure increased by only 0.23. The brochure group had a 0.37 improvement in mean scores compared with the non-brochure group, a statistically significant difference (P less than 0.0001). Affected patients who received the brochure showed greater improvement in a test on UTI-related knowledge compared with patients who did not.

The current trial assessed differences in physician and patient symptom-severity perceptions in ambulatory outpatient females with uncomplicated urinary tract infections (uUTIs). We also investigated the efficacy and safety profile of once-daily ciprofloxacin in a 500-mg PO extended-release formulation for 3 days to treat acute cystitis. This prospective, open-label, multicenter (1,972 sites), phase 4 clinical trial enrolled 7,614 adult women with a clinical diagnosis of an acute uUTI. After assessing the patient's cystitis symptoms, physicians rated each cystitis-related symptom on a 4-point severity scale. Patients independently completed a pretreatment survey including a self-assessment of these same symptoms. Clinical outcomes were assessed at the end-of-study visit (2 to 7 days post-therapy). Exact agreement on symptom severity between physician and patient was between 54% and 57% for symptoms. The discrepancies between assessments were significant in the marginal homogeneity tests (P less than 0.00001). Clinical cure following this regimen was 91.3% of efficacy-valid women. Women who had 2 or more UTI episodes in the previous 12 months tended to have lower rates of clinical cure than those who had 1 or no episodes in that time.

Significance Here, we examine the activity profile of the haloalkanoic acid dehalogenase (HAD) superfamily by screening a customized library against >200 enzymes from a broad sampling of the superfamily. From this dataset, we can infer the function of nearly 35% of the superfamily. Overall, the superfamily was found to show high substrate ambiguity, with 75% of the superfamily utilizing greater than five substrates. In addition, the HAD members with the least amount of structural accessorization of the Rossmann fold were found to be the most specific, suggesting that elaboration of the core domain may have led to increased substrate range of the superfamily. Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process.

Background The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin’s lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. Methods Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. Results Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling ( n  = 14), fatigue ( n  = 11), and pain ( n  = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. Conclusions This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL.