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.

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.

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.

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.

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.

Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer.

BACKGROUND: In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described. METHODS: In 270 Filipino and Vietnamese premenopausal patients participating in a clinical trial assessing the impact of the timing in the menstrual cycle of adjuvant surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar spine and femoral neck before this treatment, and at 6, 12, and 24 months after surgical and tamoxifen therapies. RESULTS: In women with a pretreatment BMD assessment and at least 1 other subsequent BMD assessment, no significant change in femoral neck BMD was observed over the 2-year period (-0.006 g/cm2 , -0.8%, P = .19), whereas in the lumbar spine, BMD fell by 0.045 g/cm2 (4.7%) in the first 12 months (P < .0001) and then began to stabilize. CONCLUSIONS: Surgically induced menopause with tamoxifen treatment is associated with loss of BMD at a rate that lessens over 2 years in the lumbar spine and no significant change of BMD in the femoral neck.

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.

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.

Effects on survival of menstrual cycle phase of adjuvant surgical oophorectomy in premenopausal women with breast cancer.

Adjuvant surgical oophorectomy is an effective and remarkably cost effective treatment for premenopausal women with hormone receptor positive operable breast cancer. Previously published secondary analyses indicated a survival benefit for patients whose surgery was performed in the luteal phase of the menstrual cycle as opposed to the follicular. This study utilizes additional follow-up and more fully examines this hypothesis and the general implications of long-term follow-up on trial design. Beginning in 1993 we recruited women to a multicenter randomized clinical trial of adjuvant surgical oophorectomy and tamoxifen for 5 years. We recorded the reported day 1 of the patients' last menstrual cycle on the day of their adjuvant surgery. We conducted secondary analyses of the association of history-estimated luteal or follicular phase oophorectomy surgery with disease-free and overall survival. In multivariable Cox analyses, disease-free survival (DFS) exhibited a positive trend and overall survival (OS) showed a significant improvement in patients whose surgery was estimated to have occurred in the luteal phase of the menstrual cycle compared to the follicular (HR for DFS: 0.66, 95% CI: 0.37-1.16; HR for OS: 0.49, 95% CI: 0.27-0.88). From the hazard function plots, it appears that the luteal phase surgery effect on DFS diminishes after 6 years of follow-up. In conclusion, adjuvant surgical oophorectomy during the luteal phase of the menstrual cycle resulted in a reduced hazard of recurrence as compared to oophorectomy in the follicular phase during the first 5.5 years of follow-up. The practical and biological implications of these findings deserve rigorous evaluation in clinical trials.

Breast cancer: a neglected disease for the majority of affected women worldwide.

Recent progress with declines in mortality in some high-income countries has obscured the fact that for the majority of women worldwide who are newly diagnosed, breast cancer is a neglected disease in the context of other numerically more frequent health problems. For this growing majority, it is also an orphan disease, in that detailed knowledge about tumor characteristics and relevant host biology necessary to provide even basic care is absent. With the possible exception of nutritional recommendations, current international cancer policy and planning initiatives are irrelevant to breast cancer. The progress that has occurred in high-income countries has come at extraordinary fiscal expense and patient toxicity, which of themselves suggest nonrelevance to women and healthcare practitioners in middle- and low-income countries. The implications of these circumstances appear clear: if the promise of the now 60-year-old Declaration of Human Rights that the fruits of medical science accrue to all mankind is to be realized with respect to breast cancer, a basic and translational global research initiative should be launched.

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.

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.

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.

Adjuvant hormonal therapy in premenopausal women with operable breast cancer: not-so-peripheral perspectives.

Reviews of issues around adjuvant hormonal therapies for breast cancer in premenopausal women often focus on recent and current large clinical trials, and fail to address other subjects that are very germane to evidence-based and investigatory clinical practice. These topics include: (1) the descriptive epidemiology of breast cancer globally, (2) critical issues in tumor hormone receptor testing, (3) compelling data demonstrating that hormone receptor-positive breast cancer is a chronic disease, (4) data supportive of combined hormonal therapy with tamoxifen as the standard of care, and the limited justifications for awaiting the SOFT and TEXT trial results, (5) pharmacogenetic hypotheses with tamoxifen, (6) ethical issues in ovarian suppression vs ablative treatment, and (7) emerging data about the importance of primary tumor removal surgery itself and "surgical stress" in solid tumor management.

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.

Defining a global research agenda for breast cancer.

In contrast to western high-income nations, the incidence and mortality from breast cancer are increasing in most low and middle-income countries worldwide. Current approaches to breast cancer control developed for populations of high-income societies should not be directly transferred without evaluation. A relevant research agenda includes population differences in tumor biology and metabolization of systemic therapies, cultural and psychosocial issues, and operations in healthcare systems. Highest priority should be given to assessments of clinical downstaging and basic systemic treatment effectiveness in low and middle-income populations. Partnerships of existing organizations in high-income nations with those in low and middle-income countries are currently the most feasible sources of research support.

Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer.

PURPOSE: Perillyl alcohol (POH) is a naturally occurring lipid with preclinical activity against mammary carcinomas. We conducted a phase II multi-institutional study of oral POH administered four times daily in women with advanced treatment-refractory breast cancer. METHODS: Eligible women were treated with POH four times daily at 1,200-1,500 mg m(-2) dose(-1) on a 28-day cycle. Patients tolerating 1,200 mg m(-2) day(-1) four times daily after one cycle were dose-escalated to 1,500 mg/m(2). The primary endpoint was 1-year freedom-from-progression (FFP) rate. Secondary endpoints were response rate, tolerability and correlative evaluations. RESULTS: Twenty-nine cycles of POH were administered to 14 women. Three patients were dose-escalated to 1,500 mg/m(2). Grade 1 and grade 2 gastrointestinal effects and fatigue were predominant toxicities. Of seven patients receiving up to one cycle, three stopped therapy due to intolerance. Only two patients received more than two cycles, with disease stabilization of 3 and 8 months. Thirteen patients were evaluable for response. One-year FFP rate was zero. No objective responses were seen. The median time to progression was 35 days (95% CI, 29-123 days). Median overall survival was 389 days (95% CI, 202-776 days). Pharmacokinetic parameters were similar to previous investigations. The ability to correlate plasma TGF-beta1 levels with outcome was limited by lack of clinical benefit and inter- and intra-patient variability. CONCLUSIONS: Enrollment was suspended short of planned accrual because of lack of response and poor tolerance to POH. This regimen does not appear to provide benefit in advanced treatment-refractory breast carcinoma.

Surgical oophorectomy for breast cancer: back to the future.

While the preponderance of current scientific presentations on breast cancer therapies has focused on chemotherapeutic strategies, targeted therapy with tyrosine kinase inhibitors and hormonal therapies for postmenopausal women, the majority of worldwide cases of breast cancer occur in premenopausal women, for whom practical inexpensive hormonal therapy, surgical oophorectomy, is the most common attainable treatment. In hormone-receptor-positive breast cancer, meta-analysis data from older trials, and more specific recent trial data have made clearer the chronic natural history of this broad subtype of disease and the central role of hormonal therapy in its control. Greater understanding of the critical variables in pathology procedures for breast tumor tissue hormonal receptor testing is leading to better definitions of the specific patients for whom hormonal therapies are indicated. Closer examination of outcomes following surgical oophorectomy has suggested that more than just downregulation of estrogen stimulated breast cancer growth; the reduction of systemic estrogen levels also occurs with this procedure. When combined with antiestrogen treatment using tamoxifen in patients who are active metabolizers of this drug, surgical oophorectomy is a remarkably effective and cost-effective treatment. This combination of circumstances suggests that this first hormonal therapy for breast cancer may once again, have a much greater role globally.