Deep vein thrombosis: validation of a patient-reported leg symptom index

<p>Abstract</p> <p>Introduction</p> <p>Deep vein thrombosis (DVT) is a serious health problem that affects more than 2 million people annually in the United States. Many of these patients develop asymptomatic DVT, but months to years later may experience symptomatic post-thrombotic syndrome (PTS). It is not known how many cases of PTS can be traced to "asymptomatic" DVT because venography is no longer routinely done and ultrasonography (US) may miss some asymptomatic clots. As a result, a clinical tool in addition to US to detect symptom emergence or exacerbation in patients after DVT would be of value.</p> <p>Methods</p> <p>Seventy-seven patients hospitalized with an acute DVT interviewed by telephone at 3–7 days, 30–40 days, and 12-months following discharge were included in this report. All were treated with a standard anticoagulation "Clinical Pathway Protocol" between April 1999 and January 2000. Using a 14-item Deep Vein Thrombosis Leg Symptom Index (DVT-LSI), patients were queried regarding leg pain, swelling, skin discoloration, cosmetic appearance, activity tolerance, emotional distress, and leg-related sleep problems.</p> <p>Results</p> <p>The DVT-LSI for each leg was reliable at all assessments, with instrument reliability (alpha coefficients) greater than 0.70 at all time points (range 0.71–0.87). DVT-LSI scores, and the percentage of patients exhibiting symptoms, were higher in the DVT-affected leg at all time points. Among patients with unilateral disease, symptom severity ratings were significantly worse for patients in the affected leg compared to the normal leg at all time points, with the exception of those with a right-leg DVT at 12 months. Patients with bilateral thrombi did not have different scores on one leg compared to the other.</p> <p>Conclusion</p> <p>The DVT-LSI is useful in assessing symptomatic clinical outcomes in patients after diagnosis of DVT, and may represent a surrogate marker for DVT otherwise presumed to be asymptomatic.</p

Atherosclerotic risk factor reduction in peripheral arterial diseasea: results of a national physician survey

OBJECTIVE: Individuals with peripheral arterial disease (PAD) have a 3- to 6-fold increased risk of coronary heart disease and stroke compared to those without PAD. We documented physician-reported practice behavior, knowledge, and attitudes regarding atherosclerotic risk factor reduction in patients with PAD. DESIGN: National physician survey. PATIENTS/PARTICIPANTS: General internists (N = 406), family practitioners (N = 435), cardiologists (N = 473), and vascular surgeons (N = 264) randomly identified using the American Medical Association\u27s physician database. MEASUREMENTS AND MAIN RESULTS: Physicians were randomized to 1 of 3 questionnaires describing a) a 55- to 65-year-old patient with PAD; b) a 55- to 65-year-old patient with coronary artery disease (CAD), or c) a 55- to 65-year-old patient without clinically evident atherosclerosis (no disease). A mailed questionnaire was used to compare physician behavior, knowledge, and attitude regarding risk factor reduction for each patient. Rates of prescribed antiplatelet therapy were significantly lower for the patient with PAD than for the patient with CAD. Average low-density lipoprotein levels at which physicians almost always initiated lipid-lowering drugs were 121.6 +/- 23.5 mg/dL, 136.3 +/- 28.9 mg/dL, and 149.7 +/- 24.4 mg/dL for the CAD, PAD, and no-disease patients, respectively (PCONCLUSIONS: Deficiencies in physician knowledge and attitudes contribute to lower rates of atherosclerotic risk factor reduction for patients with PAD. Reversing these deficiencies may reduce the high rates of cardiovascular morbidity and mortality associated with PAD

Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial

Background In the SPARTAN trial, addition of apalutamide to androgen deprivation therapy, as compared with placebo plus androgen deprivation therapy, significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer who were at high risk for development of metastases. We aimed to investigate the effects of apalutamide versus placebo added to androgen deprivation therapy on health-related quality of life (HRQOL).Methods SPARTAN is a multicentre, international, randomised, phase 3 trial. Participants were aged 18 years or older, with non-metastatic castration-resistant prostate cancer, a prostate-specific antigen doubling time of 10 months or less, and a prostate-specific antigen concentration of 2 ng/mL or more in serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day plus androgen deprivation therapy, or matched oral placebo plus androgen deprivation therapy, using an interactive voice randomisation system. Permuted block randomisation was used according to the three baseline stratification factors: prostate-specific antigen doubling time (>6 months vs s6 months), use of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease (NO vs Ni). Each treatment cycle was 28 days. The primary endpoint was metastasis-free survival. The trial was unblinded in July, 2017. In this prespecified exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-SD-3L questionnaires, which we collected at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1-6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter. This study is registered with ClinicalTrials.gov, number NCT01946204.Findings Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for the primary analysis, was May 19, 2017. Median follow-up for overall survival was 20.3 months (IQR 14 - 8-26. 6). FACT-P total and subscale scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group; there were similar results for EQ-5 D-3L At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for US adult men. Group mean patient-reported outcome scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group.Interpretation In asymptomatic men with high-risk non-metastatic castration-resistant prostate cancer, HRQOL was maintained after initiation of apalutamide treatment. Considered with findings from SPARTAN, patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL. Copyright (C) 2018 Elsevier Ltd. All rights reserved

Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA) : results from a double-blind, phase 3, randomised controlled trial

Background: Quality of life (QOL) has become an important complementary endpoint in cancer clinical studies alongside more traditional assessments (eg, tumour response, progression-free survival, overall survival). Niraparib maintenance treatment has been shown to significantly improve progression-free survival in patients with recurrent ovarian cancer. We aimed to assess whether the benefits of extending progression-free survival are offset by treatment-associated toxic effects that affect QOL. Methods: The ENGOT-OV16/NOVA trial was a multicentre, double-blind, phase 3, randomised controlled trial done in 107 study sites in the USA, Canada, Europe, and Israel. Patients with recurrent ovarian cancer who were in response to their last platinum-based chemotherapy were randomly assigned (2:1) to receive either niraparib (300 mg once daily) as a maintenance treatment or placebo. Randomisation was stratified based on time to progression after the penultimate platinum-based regimen, previous use of bevacizumab, and best response (complete or partial) to the last platinum-based regimen with permuted-block randomisation (six in each block) using an interactive web response system. The trial enrolled two independent cohorts on the basis of germline BRCA (gBRCA) mutation status (determined by BRACAnalysis Testing, Myriad Genetics, Salt Lake City, UT, USA). The primary endpoint of the trial was progression-free survival, and has already been reported. In this study, we assessed patient-reported outcomes (PROs) in the intention-to-treat population using the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L). We collected PROs from trial entry every 8 weeks for the first 14 cycles and every 12 weeks thereafter. If a patient discontinued, we collected PROs at discontinuation and during a postprogression visit 8 weeks (plus or minus 2 weeks) later. We assessed the effect of haematological toxic effects on QOL with disutility analyses of the most common grade 3–4 adverse events (thrombocytopenia, anaemia, and neutropenia) using a mixed model with histology, region, previous treatment, age, planned treatment, and baseline score as covariates. This study is registered with ClinicalTrials.gov, number NCT01847274. Findings: Between Aug 28, 2013, and June 1, 2015, 553 patients were enrolled and randomly assigned to receive niraparib (n=138 in the gBRCAmut cohort, n=234 in the non-gBRCAmut cohort) or placebo (n=65 in the gBRCAmut cohort, n=116 in the non-gBRCAmut cohort). The mean FOSI score at baseline was similar between the two groups (range between 25·0–25·6 in the two groups). Overall QOL scores remained stable during the treatment and preprogression period in the niraparib group; no significant differences were observed between the niraparib and placebo group, and preprogression EQ-5D-5L scores were similar between the two groups in both cohorts (0·838 [0·0097] in the niraparib group vs 0·834 [0·0173] in the placebo group in the gBRCAmut cohort; and 0·833 [0·0077] in the niraparib group vs 0·815 [0·0122] in the placebo group in the non-gBRCAmut cohort). The most common adverse events reported at screening (baseline) were lack of energy (425 [79%]; 97 [18%] reporting severe lack of energy), pain (236 [44%]), and nausea (118 [22%]). All symptoms, except nausea, either remained stable or improved over time in the niraparib group. The most common grade 3 or 4 toxicities observed in the niraparib group were haematological in nature: thrombocytopenia (124 [34%] of 367 patients), anaemia (93 [25%]), and neutropenia (72 [20%]); disutility analyses showed no significant QOL impairment associated with these toxic effects. Interpretation: These PRO data suggest that women who receive niraparib as maintenance treatment for recurrent ovarian cancer after responding to platinum treatment are able to maintain QOL during their treatment when compared with placebo. Funding: TESARO