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.

From Macro- to Microscale: A combined modelling approach for near-surface wind flow on Mars at sub-dune length-scales.

The processes that initiate and sustain sediment transport which contribute to the modification of aeolian deposits in Mars' low-density atmosphere are still not fully understood despite recent atmospheric modelling. However, detailed microscale wind flow modelling, using Computational Fluid Dynamics at a resolution of <2 m, provides insights into the near-surface processes that cannot be modeled using larger-scale atmospheric modeling. Such Computational Fluid Dynamics simulations cannot by themselves account for regional-scale atmospheric circulations or flow modifications induced by regional km-scale topography, although realistic fine-scale mesoscale atmospheric modeling can. Using the output parameters from mesoscale simulations to inform the input conditions for the Computational Fluid Dynamics microscale simulations provides a practical approach to simulate near-surface wind flow and its relationship to very small-scale topographic features on Mars, particularly in areas which lack in situ rover data. This paper sets out a series of integrated techniques to enable a multi-scale modelling approach for surface airflow to derive surface airflow dynamics at a (dune) landform scale using High Resolution Imaging Science Experiment derived topographic data. The work therefore provides a more informed and realistic Computational Fluid Dynamics microscale modelling method, which will provide more detailed insight into the surface wind forcing of aeolian transport patterns on martian surfaces such as dunes.

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.

Long COVID Patient Symptoms and its Evaluation and Management.

While the acute case burdens and deaths from the COVID-19 pandemic (in Nepal approaching 700,000 and 10,000 respectively) have been costly, the characteristics and potentially huge dimensions of the chronic disease sequelae of this infectious disease are only slowly becoming apparent. We reviewed Pub Med, major medical meeting and medical journal, and investigative journalist materials seeking to frame and describe COVID-19 chronic disease. The consequences of COVID-19 infections follow major organ damage, and induction of immunological and hormonal systems dysfunction. The first injuries are consequent to direct viral effects on tissues, and vasculitis, endothelialitis, thrombosis and inflammatory events. Pulmonary, cardiac, brain, and kidney tissues incur function-limiting damage, with dyspnea, arrythmias, decreased exercise capacity, cognitive dysfunction, and decreased glomerular filtration rates. The second process is characterized by immune dysregulation and autoimmunity, and dysfunction of hormonal regulation systems, with high, fluctuating levels of physical and mental fatigue, multiple-site pain and ache, and non-restorative sleep, in 10-30% of cases. This communication proposes evaluation and management of chronic COVID-19 patients with efficient assessment of commonest symptoms, targeted physical examination and organ function testing, and interventions based on specific organ functional status, and experience with similar chronic immune syndromes, such as myalgic encephalomyelitis.

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.

Reorganizing Hospital Cancer Care In Nepal.

While mortality rates for major common cancers- of the lung, breast, stomach, ovary, and lymphomas-- have declined significantly in high-income countries over the last decade, comparable rates for these malignancies have not fallen in Nepal. The explanations for the high-income country mortality trends are multiple and certainly include incidence reductions, but better treatments are also contributory. How to bring to Nepal the global lessons in achieving better cancer care is uncertain. We need to create an environment of ideas and a powerful vision to meet the needs for better major cancer management for Nepalis. Broadly, the Nepalese challenges are in creating more accessible and affordable care of sufficiently high-quality to make a difference. Hospitals are the major places where these issues have to be considered. To address these challenges, we offer a vision and suggest here strategies of major organizational changes in: Innovative staffing models, emphasizing teamwork, with increases in responsibilities, activities and work force percentages of non-physician health professionals; Increased outpatient care and tele-health; 3.Creating and following evidence-based diagnostic pathway and treatment clinical practice guidelines and checklists; 4. Increased application of information technology tools, particularly electronic medical records; and 5. Service implementation research evaluating quality based on structure, process and outcomes of care. Developing such effective changes requires strong community linkages, local institutional-specific coalition initiatives and experimentation, and national and international collaborations and financial support to effect practical and data-based plans and budgets. Keywords: Guidelines; improving treatment; information technology tools; outpatient services; staffing models; tele-health.

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.

Metabolomics in breast cancer: A decade in review.

Breast cancer (BC) is a heterogeneous disease which has been characterised and stratified by many platforms such as clinicopathological risk factors, genomic assays, computer generated models, and various "-omic" technologies. Genomic, proteomic and transcriptomic analysis in breast cancer research is well established, and metabolomics, which can be considered a downstream manifestation of the former disciplines, is of growing interest. The past decade has seen significant progress made within the field of clinical metabolomic BC research, with several groups demonstrating results with significant promise in the setting of BC screening and biological characterisation, as well as future potential for prognostic metabolomic biomarkers.

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.

Analysis of culturable and non-culturable bacteria and their potential to form biofilms in a primary treated dairy wastewater system.

Biofilm formation in a dairy waste irrigation system can reduce treatment capacity and increase maintenance and cleaning. An extreme biofilm observed in a primary treated dairy wastewater system blocked the irrigation line requiring manual cleaning. Both next-generation genomic sequencing and the culturable fraction showed the presence of predominantly Gram-negative bacteria. Isolates identified from current samples and stored samples from the extreme biofilm included Pseudomonas, Citrobacter, Klebsiella and Enterobacter, one Gram-positive spore former (Bacillus cereus) and one unique isolate from the biofilm, a member of the Raoultella genus. Raoultella spp was only cultured from the extreme biofilm; however, next-generation sequencing analysis of a wastewater sample showed this bacterium to be present in the wastewater system. The dominance of Gram negative may be due to the wastewater from the washing equipment used to handle raw milk. Six bacteria from the fresh samples were found to be strong biofilm formers along with the Raoultella spp from the extreme biofilm. Tests using multiple isolates showed Raoultella spp to be important in biofilm formation. This is the first report of the microbial composition of a dairy wastewater biofilm giving insight into the population and growth of microorganisms in the sections of a dairy wastewater irrigation system.

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.