Symptoms 6 months following SARS-CoV-2 infection in Nepali women.

In Nepal, over 1 million individuals have tested positive for SARS-CoV-2. We sought to describe the frequency of nonrecovery from this infection at 6 months and associated symptoms. We conducted a retrospective cohort study of 6142 women who had positive and negative PCR tests for this infection 6 months previously at 3 institutions in Kathmandu. In telephone interviews women provided information on 22 symptoms and their intensities, health status and history, and functional status. Of 3732 women who had tested PCR positive, 630 (16.9%) reported that they were unrecovered. These 630 unrecovered women were distinguished statistically from the 3102 recovered women by more frequent histories of allergies, rheumatoid disease, BCG immunization, Covid vaccination, strep throat and recent URIs, and both weight gain and weight losses of more than 5 kg in the 6 months following testing, and stressful events in the preceding year. Fatigue, pain, difficulty remembering, shortness of breath, heat and cold intolerance and unrefreshing sleep were reported in 41.9% to 10.5% of these 630 unrecovered women. Six months after confirmed SARS-CoV-2 infection 16.9% of Nepali women have long-COVID manifested as an immune, metabolic, and hormonal systems disruptive and dysfunction syndrome.

A Consecutive Series Study of the Frequencies, Intensities, and Natural History of Symptoms Following COVID-19 Infection in Nepali Men.

BACKGROUND: In Nepal, approximately one million individuals, two-thirds men, have tested positive for COVID-19. The recovery picture from this infection is undescribed. METHODS: At one major testing institution in Kathmandu, we attempted to contact men three-four months following documentation of a positive PCR Covid test. If the men contacted consented and reported that they had not completely recovered from their Covid infection, we then sought their answers about the presence and intensities of 23 symptoms. RESULTS: Of 2043 consecutive test-positive men, we successfully contacted 1254 men/or family members. 14 men had died before our calls, and two reported having cancer or tuberculosis, providing 1238 individuals. 318 (25.7%) reported that they were unrecovered and 311 of these men were successfully interviewed. At a median of 3.5 months from diagnosis, 216 (17.4%) men reported fatigue, 153 (12.4%) pain, 134 (10.8%) difficulty remembering, 133 (10.7%) reduced physical activity, 114 (9.2%) shortness of breath, and 114 (9.2%) poor sleep. By 6 and 9 months, 108 (8.7%) and 55 (4.4%) of men respectively were still unrecovered. CONCLUSIONS: In this PCR Covid test-positive series of symptomatic men, recovery was significantly prolonged compared with other viral illnesses.

Pot Song as a Novel Cancer Communication Intervention: Lessons Learned from Developing, Implementing, and Evaluating a Culturally Grounded Intervention for Breast Cancer Education in Rural Bangladesh.

Targeted public education may offer an approach to achieving more effective treatment in countries like Bangladesh, where breast cancer is a leading cause of cancer death in women. Effective cancer education interventions address the target population's cultural and contextual needs. However, there is little published literature to guide the development of educational cancer interventions in a region where lack of resources combined with cultural stigma about cancer contribute to poor breast health outcomes for women. The goal of the current study was to design, test, and evaluate a culturally grounded intervention to promote breast problem care among women in rural Bangladesh. The current manuscript first describes the process of formative evaluation that led to the development of the intervention, including decisions about the audience, message construction, and mode of intervention delivery. Second, we describe the testing process, including process and outcome evaluation. Finally, we describe the lessons learned from the process. We conclude with recommendations related to cultural grounding for message development, questionnaire design, data collection procedures, and analysis.

Cancer Prevention Strategies for Nepal.

In Nepal, the commonest major malignancies and causes of cancer death are lung, cervix, stomach, breast, head and neck (lip, mouth, pharynx, larynx), gallbladder, ovary and liver. There are seven cancer-causative exposures which should be the focus of attention such as; tobacco smoking in 29% of men, and 6% of women, solid fuel burning in 69% of homes (multiple cancers), betel-nut chewing in 40 % of men and 3% of women (head and neck cancers), alcohol abuse (liver and other cancers), Human Papilloma Virus (cervical cancer), Helicobacter pylori (stomach cancer) and Hepatitis B virus (liver cancer). To better address these reducible exposures, we suggest greater targeted strategies in three areas: Public health messaging for tobacco, solid-fuel burning, betel-nut, and alcohol; national policies for Hepatitis B virus vaccination; and analytic epidemiological and interventional research for Human Papilloma Virus and helicobacter.

Noninvasive Hemoglobin Level Prediction in a Mobile Phone Environment: State of the Art Review and Recommendations.

BACKGROUND: There is worldwide demand for an affordable hemoglobin measurement solution, which is a particularly urgent need in developing countries. The smartphone, which is the most penetrated device in both rich and resource-constrained areas, would be a suitable choice to build this solution. Consideration of a smartphone-based hemoglobin measurement tool is compelling because of the possibilities for an affordable, portable, and reliable point-of-care tool by leveraging the camera capacity, computing power, and lighting sources of the smartphone. However, several smartphone-based hemoglobin measurement techniques have encountered significant challenges with respect to data collection methods, sensor selection, signal analysis processes, and machine-learning algorithms. Therefore, a comprehensive analysis of invasive, minimally invasive, and noninvasive methods is required to recommend a hemoglobin measurement process using a smartphone device. OBJECTIVE: In this study, we analyzed existing invasive, minimally invasive, and noninvasive approaches for blood hemoglobin level measurement with the goal of recommending data collection techniques, signal extraction processes, feature calculation strategies, theoretical foundation, and machine-learning algorithms for developing a noninvasive hemoglobin level estimation point-of-care tool using a smartphone. METHODS: We explored research papers related to invasive, minimally invasive, and noninvasive hemoglobin level measurement processes. We investigated the challenges and opportunities of each technique. We compared the variation in data collection sites, biosignal processing techniques, theoretical foundations, photoplethysmogram (PPG) signal and features extraction process, machine-learning algorithms, and prediction models to calculate hemoglobin levels. This analysis was then used to recommend realistic approaches to build a smartphone-based point-of-care tool for hemoglobin measurement in a noninvasive manner. RESULTS: The fingertip area is one of the best data collection sites from the body, followed by the lower eye conjunctival area. Near-infrared (NIR) light-emitting diode (LED) light with wavelengths of 850 nm, 940 nm, and 1070 nm were identified as potential light sources to receive a hemoglobin response from living tissue. PPG signals from fingertip videos, captured under various light sources, can provide critical physiological clues. The features of PPG signals captured under 1070 nm and 850 nm NIR LED are considered to be the best signal combinations following a dual-wavelength theoretical foundation. For error metrics presentation, we recommend the mean absolute percentage error, mean squared error, correlation coefficient, and Bland-Altman plot. CONCLUSIONS: We addressed the challenges of developing an affordable, portable, and reliable point-of-care tool for hemoglobin measurement using a smartphone. Leveraging the smartphone's camera capacity, computing power, and lighting sources, we define specific recommendations for practical point-of-care solution development. We further provide recommendations to resolve several long-standing research questions, including how to capture a signal using a smartphone camera, select the best body site for signal collection, and overcome noise issues in the smartphone-captured signal. We also describe the process of extracting a signal's features after capturing the signal based on fundamental theory. The list of machine-learning algorithms provided will be useful for processing PPG features. These recommendations should be valuable for future investigators seeking to build a reliable and affordable hemoglobin prediction model using a smartphone.

Automated Cardiac Pulse Cycle Analysis From Photoplethysmogram (PPG) Signals Generated From Fingertip Videos Captured Using a Smartphone to Measure Blood Hemoglobin Levels.

Two billion people are affected by hemoglobin (Hgb) related diseases. Usual clinical assessments of Hgb are conducted by analyzing venipuncture-obtained blood samples in laboratories. A non-invasive, cheap, point-of-care and accurate Hgb test is needed everywhere. Our group has developed a non-invasive Hgb measurement system using 10-second Smartphone videos of the index fingertips. Custom hardware sets were used to illuminate the fingers. We tested four lighting conditions with wavelengths in the near-infrared spectrum suggested by the absorption properties of two primary components of blood-oxygenated Hgb and plasma. We found a strong linear correlation between our measured and laboratory-measured Hgb levels in 167 patients with a mean absolute percentage error (MAPE) of 5%. In our initial analysis, critical tasks were performed manually. Now, using the same data, we have automated or modified all the steps. For all, male, and female subjects we found a MAPE of 6.43%, 5.34%, and 4.85 and mean squared error (MSE) of 0.84, 0.5, and 0.49 respectively. The new analyses however, have suggested inexplicable inconsistencies in our results, which we attribute to laboratory measurement errors reflected in a non-normative distribution of Hgb levels in our studied patients, as well as excess noise in the specific signals we measured in the videos. Based on these encouraging results, and the promise of greater accuracy with our revised hardware and software tools, we now propose a rigorous validation study to demonstrate that this approach to hemoglobin measurement is appropriate for general clinical application.

Illness Representations of Hypertension among Nepali Patients at a Tertiary Care Hospital Clinic: An exploratory survey.

BACKGROUND: The prevalence of stage 2 hypertension approaches one-third in adult Nepalis and despite inexpensive effective treatment, long-term compliance is poor. World-wide, a major impediment is the incongruity between hypertension and patients' symptom-based illness representations. The Common-Sense Model of Self-regulation was used to investigate Nepali illness representations through open-ended interviews of patients with hypertension. METHODS: In a tertiary hospital setting, 50 self-identified hypertensive patients were interviewed about their representations of health, hypertension, and hypertensive treatment. Responses were analyzed with a modified Interpretative Phenomenological Analysis. RESULTS: An Ayurvedic-influenced health model appeared in illness identity and coping responses. Hypertension was identified as a serious disease having observable, wide-ranging symptoms with chronic and intermittent timelines. Concerns included side-effects and barriers to treatment. CONCLUSIONS: Further confirmation and investigation of Nepali common-sense hypertension models in a sample size sufficient for factor analysis is warranted for effective adherence interventions.

Clinical practice to address tamoxifen nonadherence.

The primary and secondary benefits of tamoxifen as adjuvant therapy in women with hormone-receptor-positive breast cancer are substantial: a 1% decrease in the risk of death each year for 10 years with each additional year of treatment during the first 5 years. Considerable data, however, indicate that these benefits are lost to many patients because of treatment nonadherence. Nonadherence is examined within the framework of the Common-Sense Model of Self-Regulation to describe patients' models of disease and treatment that organize their thinking and behavior, and the crucial role of the practitioner in addressing and altering these models. Common patient education and social communications about patients' hormone-receptor-positive breast cancer and tamoxifen treatment promote an acute disease paradigm in which cancer occurs within specific locations and is either present or absent. We recommend that clinicians communicate the concepts of hormone-receptor-positive breast cancer as follows: i. a non-dichotomous systemic disorder entailing a treatment goal of homeostasis and disease quiescence and ii. a disorder undetectable by currently available tests in subclinical states. Equally important, the clinician can provide a comprehensive picture of the well-documented secondary effects of tamoxifen, noting in particular the beneficial effects. Specific action plans, grounded in individual patient understanding, can be developed and reinforced, in an ongoing process that validates and integrates patient values and goals as they change over time.

Symptoms in Nepali Patients with Incurable Cancers: Implications for Interventions.

AIM: The poor quality and limited extent of palliative care services are of concern across the globe. To identify and measure patients' symptoms in Nepal, using a cell phone questionnaire platform, the investigators conducted and previously reported a cross-sectional study of Nepali adults. The unreported details of pain and other symptoms in these study data are here considered together with possible explanations and implications for interventions to lessen these symptoms. METHODS: In a "snapshot" cross-sectional study of patients under regular care in three tertiary care Nepalese centers, we questioned 383 patients with incurable cancers using a 15-item cell phone-validated instrument to describe their major current symptoms and their intensities. The distributions of 11 symptom-level scores and the correlations between pain and different symptom scores were determined. RESULTS: Thirty-eight percent of the population (142/383) had maximal pain scores which were in the severe range, and 25% (97/383) had such scores where they were evaluated. Patients reported moderate-to-severe tiredness 48% (183/383), depression 45% (172/383), anxiety 56% (217/383), poor appetite 64% (246/383), sleep quantity 64% (246/383), and sleep quality 64% (247/383). CONCLUSIONS: The significant fractions of patients with severe maximal and at-evaluation pain scores suggest that inadequate recognition and treatment of such symptoms characterized care of these regularly seen patients. The high fractions of patients with mood and sleep disturbances support this reading, suggesting helplessness and hopelessness, all addressable with psychosocial, environmental, and nontoxic, inexpensive pharmacological interventions.

Follow up after sample size re-estimation in a breast cancer randomized trial for disease-free survival.

BACKGROUND: While the clinical trials and statistical methodology literature on sample size re-estimation (SSRE) is robust, evaluation of SSRE procedures following the completion of a clinical trial has been sparsely reported. In blinded sample size re-estimation, only nuisance parameters are re-estimated, and the blinding of the current trial treatment effect is preserved. Blinded re-estimation procedures are well-accepted by regulatory agencies and funders. We review our experience of sample size re-estimation in a large international, National Institutes of Health funded clinical trial for adjuvant breast cancer treatment, and evaluate our blinded sample size re-estimation procedure for this time-to-event trial. We evaluated the SSRE procedure by examining assumptions made during the re-estimation process, estimates resulting from re-estimation, and the impact on final trial results with and without the addition of participants, following sample size re-estimation. METHODS: We compared the control group failure probabilities estimated at the time of SSRE to estimates used in the original planning, to the final un-blinded control group failure probability estimates for those included in the SSRE procedure (SSRE cohort), and to the final total control group failure probability estimates. The impact of re-estimation on the final comparison between randomized treatment groups is evaluated for those in the originally planned cohort (n = 340) and for the combination of those recruited in the originally planned cohort and those added after re-estimation (n = 509). RESULTS: Very little difference is observed between the originally planned cohort and all randomized patients in the control group failure probabilities over time or in the overall hazard ratio estimating treatment effect (originally planned cohort HR 1.25 (0.86, 1.79); all randomized cohort HR 1.24 95% CI (0.91, 1.68)). At the time of blinded SSRE, the estimated control group failure probabilities at 3 years (0.24) and 5 years (0.40) were similar to those for the SSRE cohort once un-blinded (3 years, 0.22 (0.16, 0.30); 5 years, 0.33 (0.26, 0.41)). CONCLUSIONS: We found that our re-estimation procedure performed reasonably well in estimating the control group failure probabilities at the time of re-estimation. Particularly for time-to-event outcomes, pre-planned blinded SSRE procedures may be the best option to aid in maintaining power. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00201851 . Registered on 9 September 2005. Retrospectively registered.

Symptoms In Bangladeshi Patients with Incurable Cancers: Implications for Interventions.

AIMS: The poor state of palliative care in low- and middle-income countries has been termed a global crisis by the Lancet Commission on Palliative Care. The investigators previously reported on a cross-sectional study of symptoms in 640 Bangladeshi adults with incurable cancers. Usual levels of pain were high. The not-reported details of pain and other symptoms offered an opportunity to consider explanations and implications for interventions to lessen these symptoms. METHODS: At one visit, 640 Bangladeshi patients completed a symptom questionnaire. The distributions of 12 symptom level scores and the correlations between pain and different symptom scores were determined. RESULTS: The population had significantly high and functionally compromising average usual pain scores, but low percentages of patients with very high and low pain scores. The distributions of scores for multiple symptoms were all skewed to higher mid-scale levels and modestly high (≥0.6) correlations of pain with nausea, anxiety, lack of appetite, constipation, and sleep quality were seen. CONCLUSIONS: While the types and direct effects of the cancers, the young age distribution, and the true symptomatic status of this Bangladeshi population studied may explain the described characteristics, the observations deserve exploration of other causes with specific therapeutic implications. These patients appear to have been partially treated for pain, and in particular, environmental factors such as extreme heat and its consequences appear more likely causes of moderate levels of multiple symptoms, which collectively magnified patients' suffering. Greater attention to gastrointestinal symptoms and sleep disturbance, in particular, seems indicated.

SmartHeLP: Smartphone-based Hemoglobin Level Prediction Using an Artificial Neural Network.

Blood hemoglobin level (Hgb) measurement has a vital role in the diagnosis, evaluation, and management of numerous diseases. We describe the use of smartphone video imaging and an artificial neural network (ANN) system to estimate Hgb levels non-invasively. We recorded 10 second-300 frame fingertip videos using a smartphone in 75 adults. Red, green, and blue pixel intensities were estimated for each of 100 area blocks in each frame and the patterns across the 300 frames were described. ANN was then used to develop a model using the extracted video features to predict hemoglobin levels. In our study sample, with patients 20-56 years of age, and gold standard hemoglobin levels of 7.6 to 13.5 g/dL., we observed a 0.93 rank order of correlation between model and gold standard hemoglobin levels. Moreover, we identified specific regions of interest in the video images which reduced the required feature space.

Serum Metabolomic Profiles Identify ER-Positive Early Breast Cancer Patients at Increased Risk of Disease Recurrence in a Multicenter Population.

Purpose: Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)-negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, premenopausal women with EBC who were enrolled in an international phase III trial.Experimental Design: Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic.Results: In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score.Conclusions: In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors. Clin Cancer Res; 23(6); 1422-31. ©2017 AACR.

On the road to precision, there is more practical medicine to be implemented.

Estimates are that of the annual global burden of 1.5 million new cases of breast cancer, two-thirds have hormone receptor positive tumors; a majority of these women come from low- and middle-income countries. For adjuvant patients with hormone receptor positive tumors, a major goal is identification of a "precision medicine", implying a genomic, test whose application will allow identification of those whose systemic treatment can be hormonal therapy alone. Such tests in current use are very expensive and thus in the foreseeable future are out of reach of most women who pay out of pocket. For some time it has been evident that quantitative scoring of tumors for intensity and prevalence of tumor-cell staining for estrogen or progesterone receptor (ER or PR) expression (the commonest system was first described by Allred and thus provides "Allred" scores) gives an inexpensive measure of likelihood of response to hormonal therapies - a different predictive, precision medicine tool. Majorities of hormone receptor positive tumors (one third of all patients) have "Allred" scores of 6-8 (versus scores of 3-5) for both ER and PR and these tumor-bearing patients benefit significantly more from hormonal treatments than their lowering scoring-afflicted women. When ER and PR quantitative intensity and prevalence scoring is combined with Her-2/neu testing and careful tumor histologic grading, luminal A and B type tumors can be well-defined and gene-expression testing adds little practical predictive information. For women with hormone receptor positive tumors, high quality, cost-effective "precision medicine" is available without tumor gene-expression testing.

Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer.

PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes. METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase. RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%. CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

Adjuvant Surgical Oophorectomy Plus Tamoxifen in Premenopausal Women With Operable Hormone Receptor-Positive Breast Cancer: A Global Treatment Option.

One third of annual new cases of breast cancer globally are now hormone receptor-positive tumors in premenopausal women from low- and middle-income countries. For this subgroup of women with breast cancer, high-income country guidelines suggest impractical and unaffordable adjuvant treatments. The balance of clinical trial evidence now suggests that surgical oophorectomy plus tamoxifen is a safe and practical treatment for these women in low- and middle-income countries. Additionally, new randomized trial data suggest that women in the second half of an anovulatory cycle benefit minimally from surgical oophorectomy done at this time, which implies that regularly cycling women will benefit more than has been shown from this procedure. Allred scoring of levels of hormone receptors is a practical and inexpensive approach to the assessment of magnitudes of response to oophorectomy plus tamoxifen. These circumstances suggest that more detailed consideration of this option should characterize clinical practice guidelines in high-income countries because of their global impact.

Peri-operative biology in primary breast cancer: a credible therapeutic target.

Over the last 25 years, there has been a growing body of basic science, modeling, and clinical data suggesting that the peri-operative period in the treatment of primary breast cancer is dynamic and can be manipulated to improve long-term outcomes. Clinical data have demonstrated early peaks of hazards for recurrence and emphasized the relationship of these to peri-operative events. More recently, clinical trial data with surgical oophorectomy at different times in the menstrual cycle, peri-operative progesterone, and anti-inflammatory drugs suggest that interventional studies are particularly well justified, given the increasing recognition of the costs both financially and clinically of current systemic regimens.

Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

BACKGROUND: For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. METHODS: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. RESULTS: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. CONCLUSIONS: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.