Lidia Schapira

The Influence of the Patient-Clinician Relationship on Healthcare Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes. Design Systematic review and meta-analysis. Data Sources Electronic databases EMBASE and MEDLINE and the reference sections of previous reviews. Eligibility Criteria for Selecting Studies Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions. Results Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = −.23 to .66. Using a random-effects model, the estimate of the overall effect size was small (d = .11), but statistically significant (p = .02). Conclusions This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.

Treatment of Sickle Cell Anemia with Hydroxyurea and Erythropoietin

BACKGROUND Hydroxyurea increases the production of fetal hemoglobin (hemoglobin F) in patients with sickle cell anemia and therefore has the potential for alleviating both the hemolytic and vaso-occlusive manifestations of the disease. There is preliminary evidence that recombinant human erythropoietin may also increase hemoglobin F production. METHODS AND RESULTS We treated five patients with sickle cell disease with escalating doses of intravenous erythropoietin for eight weeks. Three of these patients were subsequently treated with daily doses of oral hydroxyurea. After the optimal dose was determined, erythropoietin was then given along with hydroxyurea for four weeks. Treatment with erythropoietin, either alone or in combination with hydroxyurea, had no significant effect on the percentage of hemoglobin F-containing reticulocytes (F reticulocytes) or red cells (F cells). In contrast, hydroxyurea treatment was associated with a 3-to-25-fold increase in F reticulocytes, a 1.6-to-7-fold increase in F cells, and a 2.3-to-16-fold increase in the percentage of hemoglobin F. In all three patients given hydroxyurea, treatment with this drug was associated with reduced hemolysis, shown by decreases in serum bilirubin and lactic dehydrogenase and prolongation of red-cell survival. Hydroxyurea treatment also resulted in a decrease in the percentage of irreversibly sickled cells and sickling at partial oxygen saturation, an increase in oxygen affinity and total red-cell cation content, and a reduction in potassium-chloride cotransport. All three patients had a decrease in the number of pain crises. CONCLUSIONS This study confirms that hydroxyurea therapy increases hemoglobin F production and provides objective evidence that hydroxyurea reduces the rate of hemolysis and intracellular polymerization of hemoglobin S. In contrast, recombinant human erythropoietin, whether alone or in combination with hydroxyurea, offers no measurable benefit.

Perceptions, Knowledge, and Satisfaction With Contralateral Prophylactic Mastectomy Among Young Women With Breast Cancer: A Cross-sectional Survey

UNLABELLED Chinese translation BACKGROUND Rates of contralateral prophylactic mastectomy (CPM) have increased dramatically, particularly among younger women with breast cancer, but little is known about how women approach the decision to have CPM. OBJECTIVE To examine preferences, knowledge, decision making, and experiences of young women with breast cancer who choose CPM. DESIGN Cross-sectional survey. SETTING 8 academic and community medical centers that enrolled 550 women diagnosed with breast cancer at age 40 years or younger between November 2006 and November 2010. PATIENTS 123 women without known bilateral breast cancer who reported having bilateral mastectomy. MEASUREMENTS A 1-time, 23-item survey that included items related to decision making, knowledge, risk perception, and breast cancer worry. RESULTS Most women indicated that desires to decrease their risk for contralateral breast cancer (98%) and improve survival (94%) were extremely or very important factors in their decision to have CPM. However, only 18% indicated that women with breast cancer who undergo CPM live longer than those who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk for contralateral breast cancer, whereas women without a known mutation substantially overestimated this risk. LIMITATIONS The survey, which was administered a median of 2 years after surgery, was not validated, and some questions might have been misinterpreted by respondents or subject to recall bias. Generalizability of the findings might be limited. CONCLUSION Despite knowing that CPM does not clearly improve survival, women who have the procedure do so, in part, to extend their lives. Many women overestimate their actual risk for cancer in the unaffected breast. Interventions aimed at improving risk communication in an effort to promote evidence-based decision making are warranted. PRIMARY FUNDING SOURCE Susan G. Komen for the Cure.

Prospective Study of Fertility Concerns and Preservation Strategies in Young Women With Breast Cancer

PURPOSE Most research regarding fertility in young women with breast cancer has focused on long-term survivors. Little is known about how fertility concerns affect treatment decisions or fertility preservation strategies at the time of initial cancer diagnosis. PATIENTS AND METHODS As part of an ongoing prospective multicenter cohort study, we surveyed women with newly diagnosed early-stage breast cancer at age ≤ 40 years. The baseline survey included sociodemographic, medical, and treatment data as well as a modified Fertility Issues Survey, including fertility concern and preservation items. Univariable and multivariable modeling were used to investigate predictors of greater fertility concern. RESULTS Among the first 620 eligible respondents included in this analysis, median age was 37 years (range, 17 to 40 years); 425 women (68%) discussed fertility issues with their physicians before starting therapy, and 319 (51%) were concerned about becoming infertile after treatment. Because of concerns about fertility, four women (1%) chose not to receive chemotherapy, 12 (2%) chose one chemotherapy regimen over another, six (1%) considered not receiving endocrine therapy, 19 (3%) decided not to receive endocrine therapy, and 71 (11%) considered receiving endocrine therapy for < 5 years; 65 (10%) used fertility preservation strategies. Greater concern about fertility was associated with younger age, nonwhite race, not having children, and receipt of chemotherapy. CONCLUSION Many young women with newly diagnosed breast cancer have concerns about fertility, and for some, these substantially affect their treatment decisions. Only a minority of women currently pursue available fertility preservation strategies in this setting.

Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer

OBJECTIVE To compare markers of ovarian reserve between women exposed to cytotoxic chemotherapy for early stage breast cancer and matched controls. DESIGN Cross-sectional evaluation of markers of ovarian reserve. SETTING Dana-Farber/Brigham and Womens Cancer Center, Massachusetts General Hospital, and Faulkner Hospital in Boston, MA. PATIENT(S) Breast cancer survivors with continued menses after chemotherapy were compared with age-matched, gravidity-matched controls. MAIN OUTCOME MEASURE(S) Antral follicle count (AFC), anti-Müllerian hormone (AMH), FSH, inhibin B (InB), and E(2) on day 2, 3, or 4 of the menstrual cycle. A Bonferroni correction was performed to correct for multiple comparisons. RESULT(S) Twenty survivors and 20 controls were evaluated; 50% of survivors were currently on tamoxifen. Median AFC was 6 for survivors and 9.5 for controls. There were significant differences between the two groups in AFC, AMH, and nonsignificant differences in FSH and InB, all indicating better ovarian reserve in controls. The AFC and AMH levels were highly correlated (r = 0.72). Survivors on tamoxifen had lower AFC, AMH, InB, and higher E(2) than nontamoxifen-treated survivors. CONCLUSION(S) Premenopausal breast cancer survivors have diminished ovarian reserve compared with controls.

Body image in recently diagnosed young women with early breast cancer

To assess body image concerns among young women following a breast cancer diagnosis.

The National Cancer Institute–American Society of Clinical Oncology Cancer Trial Accrual Symposium: Summary and Recommendations

INTRODUCTION Many challenges to clinical trial accrual exist, resulting in studies with inadequate enrollment and potentially delaying answers to important scientific and clinical questions. METHODS The National Cancer Institute (NCI) and the American Society of Clinical Oncology (ASCO) cosponsored the Cancer Trial Accrual Symposium: Science and Solutions on April 29-30, 2010 to examine the state of accrual science related to patient/community, physician/provider, and site/organizational influences, and identify new interventions to facilitate clinical trial enrollment. The symposium featured breakout sessions, plenary sessions, and a poster session including 100 abstracts. Among the 358 attendees were clinical investigators, researchers of accrual strategies, research administrators, nurses, research coordinators, patient advocates, and educators. A bibliography of the accrual literature in these three major areas was provided to participants in advance of the meeting. After the symposium, the literature in these areas was revisited to determine if the symposium recommendations remained relevant within the context of the current literature. RESULTS Few rigorously conducted studies have tested interventions to address challenges to clinical trials accrual. Attendees developed recommendations for improving accrual and identified priority areas for future accrual research at the patient/community, physician/provider, and site/organizational levels. Current literature continues to support the symposium recommendations. CONCLUSIONS A combination of approaches addressing both the multifactorial nature of accrual challenges and the characteristics of the target population may be needed to improve accrual to cancer clinical trials. Recommendations for best practices and for future research developed from the symposium are provided.

Efficacy of Pegfilgrastim and Darbepoetin Alfa As Hematopoietic Support for Dose-Dense Every-2-Week Adjuvant Breast Cancer Chemotherapy

PURPOSE Dose-dense, every-2-week adjuvant chemotherapy using doxorubicin/cyclophosphamide (AC; 60/600 mg/m2 every 2 weeks x four cycles) followed by paclitaxel (175 mg/m2 every 2 weeks x four cycles), requiring filgrastim on days 3 through 10 of each cycle has been shown to improve survival compared with every-3-week treatment schedules but is associated with greater risk of RBC transfusion (13%). The role of long-acting hematopoietic growth factors in facilitating every-2-week chemotherapy and minimizing hematologic toxicity has not been established. PATIENTS AND METHODS Women with stage I to III breast cancer received dose-dense AC --> paclitaxel as neoadjuvant or adjuvant chemotherapy. Patients received pegfilgrastim 6 mg subcutaneous (SQ) on day 2 of each cycle. Darbepoetin alfa was initiated at 200 microg SQ every 2 weeks for hemoglobin < or = 12 g/dL, and administered thereafter, according to a preplanned algorithm. The primary end points were to evaluate the percentage of patients with febrile neutropenia and the percentage of patients requiring RBC transfusion. RESULTS Among 135 women treated on this single arm study, there were two cases of febrile neutropenia (incidence 1.5%). No patients received RBC transfusion. Darbepoetin alfa therapy was initiated in 92% of patients. The modest leukocytosis seen during paclitaxel cycles was attributable, in part, to corticosteroid premedication. Other toxicity and dose-delivery were similar to dose-dense AC --> paclitaxel in Cancer and Leukemia Group B 9741. CONCLUSION Pegfilgrastim and darbepoetin alfa are effective and safe in facilitating every-2-week AC --> paclitaxel, minimizing rates of febrile neutropenia and RBC transfusion.

Treatment-related amenorrhea and sexual functioning in young breast cancer survivors

Sexual dysfunction is a known complication of adjuvant therapy for breast cancer and an important determinant of quality of life. However, few studies have explored how treatment and other factors affect sexual functioning in young breast cancer survivors.

Breast cancer presentation and diagnostic delays in young women

Young women may experience delays in diagnosis of breast cancer, and these delays may contribute to poorer outcomes.