Idiopathic thrombocytopenic purpura treated with steroid therapy does not prevent acute myocardial infarction: a case report.

We report the case of a 65-year-old man affected by idiopathic thrombocytopenic purpura, who developed an acute myocardial infarction after 2 years of steroid therapy. Thrombocytopenia was initially recognized 11 years earlier, and became severe during the past 2 years [platelets (PLTS) 10000-30000/microl]. He was treated with steroids, initially to perform a surgical procedure (prednisone 75 mg/day), subsequently to maintain a platelet count of about 50000/microl (prednisone 12.5 mg/day). After 1 year of treatment, he began to complain about exertional angina and dyspnea. His blood pressure became elevated and cholesterol level raised. The exercise electrocardiogram, previously manifesting ischaemic changes, normalized after 1 month of steroid wash-out; however, steroid therapy was reinstituted (prednisone 5 mg per day). One year later, he suffered an infero-lateral non-Q-wave myocardial infarction. It seems likely that the severe coronary atherosclerosis present in our patient developed despite a low platelet count, under the spur of a heavier risk factor profile. Steroid therapy could have had a role as a precipitating agent of the acute event, and the opportunity of alternative treatments is considered.     

Lapatinib plus capecitabine versus capecitabine alone for HER2+ (ErbB2+) metastatic breast cancer: quality-of-life assessment

The randomized phase III trial EGF100151 demonstrated that the combination of lapatinib plus capecitabine (L + C) significantly improved time to progression (TTP) compared with capecitabine alone (C) in heavily pretreated patients with HER2+ (ErbB2+) advanced or metastatic breast cancer. This analysis assessed the effects of study treatments on quality of life (QOL) among patients in EGF100151. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and EuroQoL (EQ-5D) questionnaires. Patients completed questionnaires during efficacy and safety assessment visits (i.e., at screening visit, every 6 weeks for the first 24 weeks, every 12 weeks thereafter, and at discontinuation of study treatment). Primary analyses compared the treatment groups based on change from baseline QOL. Exploratory analyses compared proportion of patients achieving minimum important differences (MID) in QOL scores and the relationship between QOL and tumor status. Quality of life for patients in both treatment groups was maintained during 24 weeks of follow-up. Adjusted mean changes from baseline in all QOL scores for the L + C arm were comparable to those for the C arm. The between-group differences ranged from 0.7 to 2.2 (FACT-B total) and 0.3 to 1.8 (EQ-5D visual analog scale) and were consistently in favor of the L + C arm, although not statistically significant. Patients with an objective tumor response or stable disease showed clinically meaningful differences in QOL scores compared to patients with progressive disease. A greater proportion of patients receiving L + C versus C achieved the MID for all five QOL scores, although differences were not statistically significant. The addition of lapatinib to capecitabine significantly increases TTP without any evidence of a deleterious effect on patients’ QOL, confirming its clinical benefit in this heavily pretreated patient population with advanced HER2+ breast cancer that has progressed on trastuzumab therapy.     

Health-related quality of life in patients with neuroendocrine tumors: an investigation of treatment type,disease status,and symptom burden

Introduction

Neuroendocrine tumors (NETs) are malignant solid tumors arising in hormone-secreting tissue. They have historically been very difficult to treat, and advanced NETs are considered incurable. Surgery is the only potentially curative treatment option, though research is ongoing, investigating the efficacy of targeted therapies combined with more traditional chemotherapies. Frequent bowel movements and episodes of flushing are the most common symptoms.

Methods

The present study reports data from an anonymous patient survey of 663 eligible NET patients, identified with the assistance of patient advocacy groups. This study investigated the impact of treatment (surgery alone; surgery plus somatostatin analogue; other treatments) on quality of life (QOL). Finally, we investigate whether recurrent disease results in poorer QOL compared to disease treated curatively with surgery and remaining in remission.

Results and discussion

Results suggest that increased frequency of bowel movements and presence of any flushing symptoms are correlated with decreased quality of life. Treatment groups differed on most Patient Reported Outcomes Measurement Information System (PROMIS) global health and PROMIS-29 scores, including physical function, fatigue, pain, social function, and general physical and mental health, with the surgery group reporting significantly better scores than the other groups (effect size of differences ranged from 0.28 to 0.54). This may be possibly due to effective symptom control reached for these patients through surgery alone. After adjustment for carcinoid syndrome, the association with the treatment group disappeared for all domains except physical functioning. In terms of disease status, patients with recurrent disease reported poorer physical, social, and mental functions. Depression scores were similar between groups; however, patients with recurrent disease reported significantly higher anxiety compared to those with no current NET. Physical functioning was even more markedly different between groups, with recurrent NET patients reporting significantly impaired overall physical function, impaired sleep, and significant fatigue compared to those with no current NET. To our knowledge, this is the first study to comprehensively examine the effect of treatment group, disease status, and symptom burden on the quality of life in NET patients in a large sample. Limitations and future research directions are discussed.

     

Effects of low-molecular-weight heparin on platelets as compared with commercial heparin

Five subjects were injected with 5,000 IU of commercial heparin and low-molecular-weight heparin at an interval of 20 days after each injection. Both heparins produced the same platelet factor 4 release immediately after administration (commercial heparin 114.6 +/- 21.6 ng/ml, low-molecular-weight heparin 113.1 +/- 22.1 ng/ml). However, commercial heparin induced a more evident potentiating effect on ADP-induced platelet aggregation and was still present 60 min after injection. Low-molecular-weight heparin had a higher anti-Xa-specific activity than that determined by activated partial thromboplastin time. The opposite was true for the commercial preparation.     

U.K. utility weights for the EORTC QLU‐C10D

The EORTC QLU‐C10D is a new multi‐attribute utility instrument derived from the widely used cancer‐specific quality of life questionnaire, EORTC QLQ‐C30. It contains 10 dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems), each with four levels. The aim of this study was to provide U.K. general population utility weights for the QLU‐C10D. A U.K. online panel was quota‐sampled to align the sample to the general population proportions of sex and age (≥18 years). The online valuation survey included a discrete choice experiment (DCE). Each participant was asked to complete 16 choice‐pairs, each comprising two QLU‐C10D health states plus duration. DCE data were analysed using conditional logistic regression to generate utility weights. Data from 2,187 respondents who completed at least one choice set were included in the DCE analysis. The final U.K. QLU‐C10D utility weights comprised decrements for each level of each health dimension. For nine of the 10 dimensions (all except appetite), the expected monotonic pattern was observed across levels: Utility decreased as severity increased. For the final model, consistent monotonicity was achieved by merging inconsistent adjacent levels for appetite. The largest utility decrements were associated with physical functioning and pain. The worst possible health state (the worst level of each dimension) is ?0.083, which is considered slightly worse than being dead. The U.K.‐specific utility weights will enable cost–utility analysis (CUA) for the economic evaluation of new oncology therapies and technologies in the United Kingdom, where CUA is commonly used to inform resource allocation.     

Establishing clinically-relevant terms and severity thresholds for Patient-Reported Outcomes Measurement Information System® (PROMIS®) measures of physical function,cognitive function,and sleep disturbance in people with cancer using standard setting

Quality of Life Research - Patient-Reported Outcomes Measurement Information System® (PROMIS®) physical function, cognitive function, and sleep disturbance measures are increasingly used...     

Modeling strategies to improve parameter estimates in prognostic factors analyses with patient-reported outcomes in oncology

Purpose

The inclusion of patient-reported outcome (PRO) questionnaires in prognostic factor analyses in oncology has substantially increased in recent years. We performed a simulation study to compare the performances of four different modeling strategies in estimating the prognostic impact of multiple collinear scales from PRO questionnaires.

Methods

We generated multiple scenarios describing survival data with different sample sizes, event rates and degrees of multicollinearity among five PRO scales. We used the Cox proportional hazards (PH) model to estimate the hazard ratios (HR) using automatic selection procedures, which were based on either the likelihood ratio-test (Cox-PV) or the Akaike Information Criterion (Cox-AIC). We also used Cox PH models which included all variables and were either penalized using the Ridge regression (Cox-R) or were estimated as usual (Cox-Full). For each scenario, we simulated 1000 independent datasets and compared the average outcomes of all methods.

Results

The Cox-R showed similar or better performances with respect to the other methods, particularly in scenarios with medium–high multicollinearity (ρ?=?0.4 to ρ?=?0.8) and small sample sizes (n?=?100). Overall, the Cox-PV and Cox-AIC performed worse, for example they did not select one or more prognostic collinear PRO scales in some scenarios. Compared with the Cox-Full, the Cox-R provided HR estimates with similar bias patterns but smaller root-mean-squared errors, particularly in higher multicollinearity scenarios.

Conclusions

Our findings suggest that the Cox-R is the best approach when performing prognostic factor analyses with multiple and collinear PRO scales, particularly in situations of high multicollinearity, small sample sizes and low event rates.