Publications

PURPOSE

Approximately 20 % of patients develop lymphedema (LE) following breast cancer (BC) surgery. An evaluation of distinct trajectories of volume change may improve our ability to diagnose LE sooner. The purposes of this study were to identify subgroups of women with distinct trajectories of limb volume changes following BC surgery and to evaluate for phenotypic differences among these classes.

METHODS

In this prospective longitudinal study, 380 women were enrolled prior to unilateral BC surgery. Upper limb bioimpedance was measured preoperatively and serially for 1 year postoperatively. Resistance ratios (RRs) were calculated. A RR of >1 indicates affected limb volume > unaffected limb volume. Latent class growth analysis (LCGA) was used to identify classes of women with distinct postoperative RR trajectories. Differences among classes were evaluated using analyses of variance and chi-square analyses.

RESULTS

Three distinct classes were identified as follows: RR <0.95 (37.9 %), RR ~1.00 (46.8 %), and RR >1.05 (15.3 %). Patients in the RR >1.05 class were more likely to have diabetes (p = 0.036), were more likely to have BC on their dominant side (p < 0.001), had higher RR ratios at the preoperative and 1-month assessments (p < 0.001), and were more likely to be diagnosed with LE (p < 0.001).

CONCLUSIONS

LCGA is a useful analytic technique to identify subgroups of women who may be at higher risk for the development of LE, based on trajectories of limb volume change after BC surgery.

IMPLICATIONS FOR CANCER SURVIVORS

Assessment of preoperative and 1-month bioimpedance RRs may allow for the earlier identification of patients who are at higher risk for the development of LE.

INTRODUCTION

Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC).

MATERIAL AND METHODS

Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) every 21days as IC. Afatinib was started at a dose of 20mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40mg/m(2) weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0.

RESULTS

Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities.

CONCLUSIONS

The MTD of afatinib given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) is 20mg daily. Combination of afatinib at doses higher than 20mg with carboplatin and paclitaxel should be administered with caution due to the toxicities.

Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring.

BACKGROUND

Medication decision-making poses a challenge for a significant proportion of patients. This is an even more challenging for patients who have complex, rare, immune conditions that affect them at a young age and are associated with the use of life-long treatment, perceived by some as having significant risk of side effects and toxicity.

INTRODUCTION

The aim of our study was to examine the perspectives of women with lupus nephritis on facilitators to medication decision-making.

METHODS

We used the nominal group technique (NGT), a structured formative process to elicit patient perspectives. An NGT expert moderated eight patient group meetings. Participants (n = 52) responded to the question "What sorts of things make it easier for people to decide to take the medicines that doctors prescribe for treating their lupus kidney disease?" Patients nominated, discussed, and prioritized facilitators to medication decisional processes.

RESULTS

Fifty-two women with lupus nephritis participated in eight NGT meetings (27 African-American, 13 Hispanic, and 12 Caucasian). Average age was 40.6 years (standard deviation (SD) = 13.3), and disease duration was 11.8 years (SD = 8.3); 36.5 % obtained at least a college education, and 55.8 % had difficulty in reading health materials. Patients generated 280 decision-making facilitators (range of 26 to 42 per panel). Of these, 102 (36 %) facilitators were perceived by patients as having relatively more influence in decision-making processes than others. Prioritized facilitators included effective patient-physician communication regarding benefits/harms, patient desire to live a normal life and improve quality of life, concern for their dependents, experiencing benefits and few/infrequent/no harms with lupus medications, and their affordability. Relative to African-Americans, Caucasian and Hispanic patients endorsed a smaller percentage of facilitators as influential. Level of agreement with which patients within panels independently agreed in their selections of the three most influential facilitators ranged from 33 % to 60 %.

CONCLUSIONS

We identified facilitators to lupus medication decision-making. This information will be used to populate a decision aid for lupus nephritis.

Primary and primordial prevention of cardiovascular disease (CVD) requires not only identification of risk factors, but also appropriate and timely therapy. In order to prevent the expected increase in prevalence of CVD, it is essential that clinicians are aware of behavioral cardiovascular risk factors. A basic review is critical to clarify the difference between physical activity and fitness, as well as to discuss the role each plays in cardiovascular outcomes. We discuss observational epidemiological studies and randomized control trials that have examined the effect of physical activity and cardiorespiratory fitness on CVD.