Strengths and opportunities for improvement in surgical education in Ukraine: A qualitative study.

BACKGROUND: The full-scale invasion of Ukraine by Russia in 2022 has significantly impacted the country's healthcare system including surgical education. To assess the current state and identify the strengths and opportunities for the improvement of Ukraine's surgical education system during the peri-war period, this study is one of the first to explore the state of surgical education across Ukraine in peri-war, providing essential insights for current and postwar healthcare reconstruction. METHODS: This qualitative study involved semi-structured interviews with 24 Ukrainian surgical residents, surgeons, and program leadership from various regions. The study focused on clinical training, didactics, mentorship, autonomy, resident evaluation, the impact of war, and gender disparities in surgical education. Data analysis was conducted using a rapid qualitative analysis technique. RESULTS: Interviews revealed strengths in surgical education such as adaptability to war conditions and international collaborations. However, opportunities for improvement were identified including a lack of structured clinical and didactic experiences, limited autonomy and access to simulators, gender discrimination, and war-time challenges. These issues highlight a need for more comprehensive training and support systems for surgical trainees in Ukraine. CONCLUSIONS: The study underscores the resilience and adaptability of Ukrainian surgical education in the face of war while also emphasizing the need for significant improvements. It calls for implementing structured training programs, enhanced mentorship, and attention to gender equality. These findings are crucial for improving surgical education in Ukraine and can be used as an example for other lower-middle-income countries, especially in conflict settings.

Enhancing the utilization of healthy living interventions among cancer survivors in historically underserved populations and communities.

PURPOSE: This study aimed to describe the clinical characteristics and wellness programming preferences of cancer survivors from Acres Homes, a historically Black neighborhood in Houston, Texas, with areas of persistent poverty. The goal of this study was to identify opportunities to increase cancer survivor utilization of healthy eating and active living interventions aligned to cancer center community outreach and engagement efforts. METHODS: This multiple methods study included a retrospective review of electronic health record data (n = 413) and qualitative interviews with cancer survivors (n = 31) immediately preceding initiation of healthy eating, active living programming in Acres Homes. RESULTS: This study found Acres Homes survivors have high rates of co-occurrent cardiometabolic disease including obesity (45.0%), diabetes (30.8%), and other related risk factors as well as treatment-related symptoms. Four major concepts emerged from interviews: (1) Factors that influence survivors' ability to eat well and exercise, (2) Current usage of community resources, (3) Interest in relevant programming, and (4) Specific programming preferences. Opportunities for current and future health promotion programming for cancer survivors were explored. CONCLUSION: Strategically tailoring community resources for cancer survivors can provide a more robust network of support to promote healthy eating and active living in this population. This work informed community implementation of evidence-based health interventions in Acres Homes and may support future projects aiming to enhance community-led cancer prevention efforts in historically underserved communities.

Access to and Affordability of World Health Organization Essential Medicines for Cancer in Sub-Saharan Africa: Examples from Kenya, Rwanda, and Uganda.

BACKGROUND: Cancer mortality is high in sub-Saharan Africa (SSA), partly due to inadequate treatment access. We explored access to and affordability of cancer treatment regimens for the top 10 cancers utilizing examples from Kenya, Uganda, and Rwanda. MATERIALS AND METHODS: Population, healthcare financing, minimum wage, and cancer incidence and mortality data were obtained from the WHO, World Bank, public sources, and GLOBOCAN. National Essential Medicines List (NEML) alignment with 2019 WHO EML was assessed as a proportion. Cancer regimen pricing was calculated using public and proprietary sources and methods from prior studies. Affordability through universal healthcare coverage (UHC) was assessed as 1-year cost <3× gross national income per capita; and to patients out-of-pocket (OOP), as 30-day treatment course cost <1 day of minimum wage work. RESULTS: A total of 93.4% of the WHO EML cancer medicines were listed on the 2019 Kenya NEML, and 70.5% and 41.1% on Uganda (2016) and Rwanda (2015) NEMLs, respectively. Generic chemotherapies were available and affordable to governments through UHC to treat non-Hodgkin's lymphoma, cervical, breast, prostate, colorectal, ovarian cancers, and select leukemias. Newer targeted agents were not affordable through government UHC purchasing, while some capecitabine-based regimens were not affordable in Uganda and Rwanda. All therapies were not affordable OOP. CONCLUSION: All cancer treatment regimens were not affordable OOP and some were not covered by governments. Newer targeted drugs were not affordable to all 3 governments. UHC of cancer drugs and improving targeted therapy affordability to LMIC governments in SSA are key to improving treatment access and health outcomes.

Perspectives of Zambian Clinical Oncology Trainees in the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART).

BACKGROUND: African countries are underrepresented in cancer research, partly because of a lack of structured curricula on clinical research during medical education. To address this need, the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART) was developed jointly by MD Anderson Cancer Center (MDA) and the Cancer Diseases Hospital in Zambia (CDH) for Zambian clinical oncology trainees. We explored participant perspectives to provide insight for implementation of similar efforts. MATERIALS AND METHODS: The MD Anderson and Zambia Virtual Clinical Research Training Program consisted of weekly virtual lectures and support of Zambian-led research protocols through longitudinal mentorship groups that included CDH faculty and MDA peer and faculty mentors. Participants were contacted via email to take part in semi-structured interviews, which were conducted via teleconference and audio-recorded, transcribed, and coded. Emergent themes were extracted and are presented with representative verbatim quotations. RESULTS: Thirteen of the 14 (93%) trainees were interviewed. Emergent themes included (1) participants having diverse educational backgrounds but limited exposure to clinical research, (2) importance of cancer research specific to a resource-constrained setting, (3) complementary roles of peer mentors and local and international faculty mentors, (4) positive impact on clinical research skills but importance of a longitudinal program and early exposure to clinical research, and (5) challenges with executing research protocols. CONCLUSION: To our knowledge, this is the first qualitative study of African clinical oncology trainees participating in a virtual clinical research training program. The lessons learned from semi-structured interviews with participants in MOZART provided valuable insights that can inform the development of similar clinical research training efforts and scale-up.

The effect of non-AIDS-defining cancers on people living with HIV.

Non-AIDS-defining cancers are a growing source of morbidity for people with HIV globally. Although people living with HIV have a disproportionately increased risk of developing virally mediated cancers, cancer burden for common non-AIDS-defining cancers that are not virally associated and are linked to ageing, such as prostate cancer, is becoming higher than for virally mediated cancers. Ageing, behavioural, and HIV-specific factors drive the incidence and affect the outcomes of non-AIDS-defining cancers, presenting different challenges for addressing global morbidity and mortality from non-AIDS-defining cancer. Although large population-based studies have shown that people living with HIV with non-AIDS-defining cancers have poorer cancer outcomes than do people without HIV, current guidelines emphasise that people living with HIV with non-AIDS-defining cancers should receive standard, guideline-based treatment, and infectious disease and oncology providers should work closely to address potential drug interactions between antiretroviral therapy and antineoplastic treatment. Most trials target preventive measures focusing on non-AIDS-defining cancers. However, treatment trials for the optimal management of people living with HIV and non-AIDS-defining cancer, including interventions such as immunotherapies, are needed to improve non-AIDS-defining cancer outcomes.

Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307).

PURPOSE: Bisphosphonates reduce bone metastases in postmenopausal women with early-stage breast cancer but carry the risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We describe risk factors for BRONJ and compare BRONJ provoked by infection or trauma with spontaneous lesions, which carry a better prognosis. METHODS: SWOG 0307 randomized women with stage I-III breast cancer to receive zoledronic acid (ZA), clodronate (CL), or ibandronate (IB) for 3 years, implemented BRONJ prevention guidelines, and collected information about dental health and development of BRONJ. All statistical tests were two-sided. RESULTS: Of 6018 women, 48 developed BRONJ. Infection was present in 21 (43.8%). Median time to BRONJ was 2.1 years for ZA, 2.0 years for IB, and 3.4 years for clodronate (p = 0.04). BRONJ was associated with bisphosphonate type (28/2231 (1.26%) for ZA, 8/2235 (0.36%) for CL, 12/1552 (0.77%) for IB), dental calculus (OR 2.03), gingivitis (OR 2.11), moderate/severe periodontal disease (OR 2.87), and periodontitis > 4 mm (OR 2.20) (p < 0.05). Of 57 lesions, BRONJ occurred spontaneously in 20 (35.1%) and was provoked by dental extraction in 20 (35.1%), periodontal disease in 14 (24.6%), denture trauma in 6 (10.5%), and dental surgery in 2 (3.5%). Spontaneous BRONJ occurred more frequently at the mylohyoid ridge. There were no differences in dental disease, infection, or bisphosphonate type between spontaneous and provoked BRONJ. CONCLUSION: ZA and worse dental health were associated with increased incidence of BRONJ, with a trend toward additive risk when combined. BRONJ incidence was lower than in similar studies, with prevention strategies likely linked to this. CLINICAL TRIAL NUMBER: NCT00127205 REGISTRATION DATE: July 2005.

Breast cancer patient advocacy: A qualitative study of the challenges and opportunities for civil society organizations in low-income and middle-income countries.

BACKGROUND: Breast cancer advocacy movements, driven by advocate-led civil society organizations (CSOs), have proven to be a powerful force for the advancement of cancer control in high-income countries (HICs). However, although patient advocacy movements are growing in low-income and middle-income countries (LMICs) in response to an increasing cancer burden, the experiences and needs of advocate-led breast cancer CSOs in LMICs is understudied. METHODS: The authors conducted a qualitative study using in-depth interviews and focus group discussions with 98 participants representing 23 LMICs in Eastern Europe, Central Asia, East and Southern Africa, and Latin America. RESULTS: Despite geographic, cultural, and socioeconomic differences, the common themes that emerged from the data across the 3 regions are strikingly similar: trust, knowledge gaps, stigma, sharing experiences, and sustainability. The authors identified common facilitators (training/education, relationship building/networking, third-party facilitators, and communication) and barriers (mistrust, stigma, organizational fragility, difficulty translating HIC strategies) to establishing trust, collaboration, and advancing cancer advocacy efforts. To the authors' knowledge, the current study is the first to describe the role that coalitions and regional networks play in advancing breast cancer advocacy in LMICs across multiple regions. CONCLUSIONS: The findings of the current study corroborate the importance of investing in 3-way partnerships between CSOs, political leaders, and health experts. When provided with information that is evidence-based and resource appropriate, as well as opportunities to network, advocates are better equipped to achieve their goals. The authors propose that support for CSOs focuses on building trust through increasing opportunities for engagement, disseminating best practices and evidence-based information, and fostering the creation of platforms for partnerships and networks.

Building an Effective International Medical Evacuation Program for Ukrainian Patients With Cancer Amid Prolonged Military Conflict.

PURPOSE: During military conflicts, the immediate response to a severely disrupted health care system often overlooks the needs of patients with cancer who require continuous specialized care. The full-scale Russian invasion of Ukraine in February 2022 was no exception, leaving many Ukrainian patients without access to essential care. MATERIALS AND METHODS: We conducted a retrospective cohort study to assess the impact of the MedEvac program, facilitating the transfer of Ukrainian patients with cancer to European Union (EU) institutions for treatment, and to describe its components. Patient data from the Ministry of Health of Ukraine (MOH) database (April 2022-April 2023) were analyzed. RESULTS: Of 639 applications in the MOH database, 339 (53.1%) had sufficient data for analysis and, of those, 281 (82.9%) were evacuated to EU hospitals. Median age of evacuated patients was 47 (IQR, 38-58) years and most were newly diagnosed (94.0%, n = 264). Predominantly, patients were evacuated for systemic cancer therapy (81.9%, n = 230). Multivariate logistic regression analysis revealed that a good performance status (Eastern Cooperative Oncology Group 0-2) was the most significant factor associated with evacuation (odds ratio [OR], 9.64 [95% CI, 3.08 to 30.23]). Patients with melanoma were more likely to be evacuated, even after adjustment for performance status (OR, 2.56 [95% CI, 1.14 to 5.72]), while patients with head and neck cancer were significantly less so (OR, 0.20 [95% CI, 0.06 to 0.72]). CONCLUSION: MedEvac program provides a viable model for medical evacuation and management of patients with cancer amid prolonged military conflict, highlighting the importance of international cooperation and setting a precedent for other crisis responses. Continuous evaluation and adaptation are essential to ensure the program's effectiveness and sustainability.

Factors Affecting Colorectal Cancer Screening in Primary Care Physician Practices in Ukraine.

PURPOSE: This study aims to identify the factors influencing colorectal cancer (CRC) screening practices, along with the barriers and facilitators from the perspective of primary care physicians (PCPs) in Ukraine. Considering health care system challenges, including those posed by the ongoing war, this research seeks to inform improvements in CRC screening and outcomes in Ukraine and other low- and middle-income countries (LMICs). METHODS: A survey was designed and distributed electronically to Ukrainian PCPs, focusing on CRC screening practices, beliefs, and barriers. The survey incorporated questions adapted from established cancer screening surveys and frameworks. Complete responses were collected from 740 PCPs. Sample statistics were computed, and population-level perceptions and associations with CRC screening practices were estimated by standardizing responses to national PCP demographics. RESULTS: The majority of respondents were women (91%) and specialized in family medicine (84%). Respondents believed in the effectiveness of colonoscopy for reducing CRC mortality (80%), with 75% of PCPs referring patients for this screening modality. Major barriers identified include inadequate training of PCPs in screening and lack of resources. Respondents reported high utilization of fecal occult blood test and colonoscopy for screening when these tests were said to be available in their practices. Self-reported familiarity with CRC screening guidelines and participation in educational workshops were positively associated with screening referrals. CONCLUSION: The study highlights the role of access to CRC screening tests and awareness of screening guidelines in enhancing CRC screening practices among Ukrainian PCPs. Addressing training and resource barriers, alongside public health interventions targeting patient-related barriers, is essential. These findings offer valuable insights for LMICs facing similar challenges, emphasizing the need for tailored strategies to improve cancer screening in these health care settings.

Circulating natural killer cells and their association with breast cancer and its clinico-pathological characteristics.

Purpose: Natural killer (NK) cells play a critical role in cancer immunosurveillance and hold promise as both therapies and prognostic markers in advanced disease. We explore factors that may influence NK cell concentration in the peripheral blood of women with breast cancer in Côte d'Ivoire compared to healthy controls and implications for future research in our context. Methods: In this cross-sectional case-control study, blood samples were taken from 30 women diagnosed with breast cancer within 6 months of diagnosis and fifteen healthy women at University Teaching Hospital [Centre Hospitalier Universitaire (CHU)] Treichville in Abidjan, Côte d'Ivoire, from March to September 2018. The blood draw could take place at any time following diagnosis and through treatment. Demographic and clinical data were collected. NK cells were isolated, stained, analysed and counted using the flow cytometer at the Department of Immunology at CHU of Cocody. All p-values were two-sided. Results: Mean age among 30 women with breast cancer was 49 years old compared to 45 years old for 15 controls (p = 0.41). Among 30 women with breast cancer, 4 (13.3%) had Stage 2 disease, 14 (46.7 %) at Stage 3, and 12 (40%) at Stage 4. Fourteen (46.7%) had breast cancer that was hormone receptor-positive (HR+) HER2-negative, 10 (33.3%) had triple-negative cancer, three (10.0%) had HR+HER2+ disease, and three (10.0%) HR-HER2+ cancer. NK cell concentration was not associated with cancer diagnosis, age, cancer stage, subtype, or type of treatment patients received (p > 0.05). Conclusion: Although we did not find an association between NK cell concentration, cancer characteristics or treatment, our results be limited by the small sample size and timing of blood draw. Our next steps include a larger study to explore circulating NK cells prior to any treatment and NK cell infiltration within breast cancer tumour and correlating this with response to treatment and prognosis.

Building Capacity for Cancer Research in the Era of COVID-19: Implementation and Results From an International Virtual Clinical Research Training Program in Zambia.

PURPOSE: The incidence of cancer in sub-Saharan Africa is increasing rapidly, yet cancer research in the region continues to lag. One contributing factor is limited exposure to clinical research among trainees. We describe implementation and results of a virtual clinical research training program for Zambian clinical oncology fellows developed jointly by the Cancer Diseases Hospital in Zambia and the MD Anderson Cancer Center to address this need. METHODS: The clinical research training program consisted of 14 weekly virtual lectures, development of research questions by Zambian clinical oncology fellows, assignment of faculty and peer mentors, longitudinal mentorship of research protocols, and anonymous precourse and postcourse surveys. The paired t-test was used to analyze the change in academic self-efficacy scores. RESULTS: Fourteen Zambian clinical oncology fellows participated. Senior fellows were paired with research mentors, leading to the development of eight research protocols. A total of 70 meetings and 126 hours of mentorship occurred with a median of seven meetings and 15 hours per pairing. The precourse and postcourse survey response rates were 86% and 79%, respectively. There were statistically significant increases in nine of 12 academic self-efficacy domains. The largest gains were in ability to independently perform research (P < .001) and research mentorship (P = .02) with an average increase of 1.5 points on a five-point scale in both domains. CONCLUSION: The Cancer Diseases Hospital MD Anderson Cancer Center clinical research training program for Zambian clinical oncology fellows led to increases in multiple academic self-efficacy domains among participants, formation of longitudinal mentorship groups with both faculty and peer mentors, and development of Zambian-led research protocols, demonstrating the feasibility of implementing a virtual model. This may be especially relevant because of shifting international collaboration paradigms after the COVID-19 pandemic.

Action for Increasing Diversity, Market Access, and Capacity in Oncology Registration Trials-Is Africa the Answer? Report From a Satellite Session of the Accelerating Anti-Cancer Agent Development and Validation Workshop.

Patients of African ancestry are not well-represented in cancer clinical trials despite bearing a disproportionate share of mortality both in United States and Africa. We describe key stakeholder perspectives and priorities related to bringing early-stage cancer clinical trials to Africa and outline essential action steps. Increasing Diversity, Market Access, and Capacity in Oncology Registration Trials-Is Africa the Answer? satellite session was organized at 2021 Accelerating Anti-Cancer Agent Development and Validation Workshop. Panelists included representatives of African Organization for Research and Training in Cancer, Uganda Cancer Institute, Uganda Women's Cancer Support Organization, BIO Ventures for Global Health, Bill & Melinda Gates Foundation, the US Food and Drug Administration, Nigeria's National Agency for Food and Drug Administration and Control, Bayer, and Genentech, with moderators from ASCO and American Cancer Society. Key discussion themes and resulting action steps were agreed upon by all participants. Panelists agreed that increasing diversity in cancer clinical trials by including African patients is key to ensuring novel drugs are safe and effective across populations. They underscored the importance of equity in clinical trial access for patients in Africa. Panelists discussed their values related to access and barriers to opening clinical trials in Africa and described innovative solutions from their work aimed at overcoming these obstacles. Multisectoral collaboration efforts that allow leveraging of limited resources and result in sustainable capacity building and mutually beneficial long-term partnerships were discussed as key to outlined action steps. The panel discussion resulted in valuable insights about key stakeholder values and priorities related to bringing early-stage clinical trials to Africa, as well as specific actions for each stakeholder group.

Advancing Breast Cancer Advocacy in Eastern Europe and Central Asia: Findings From Women's Empowerment Cancer Advocacy Network (WE CAN) Summits.

PURPOSE: Breast cancer civil society organizations have emerged in Eastern Europe and Central Asia to raise awareness about cancer as a survivable disease and provide patient support. We explored the experiences and priorities of these organizations with the goal of making recommendations to advance cancer advocacy and improve cancer care. METHODS: We conducted in-depth interviews and focus group discussions with representatives of civil society organizations attending the 7th Women's Empowerment Cancer Advocacy Network Summit in Romania in 2015. Interviews were audiorecorded, transcribed, coded, and analyzed for key themes. Findings were discussed at the 8th Women's Empowerment Cancer Advocacy Network Summit in Ukraine in 2017 to ensure accuracy. RESULTS: We conducted nine in-depth interviews and three focus group discussions with a total of 36 participants. Survivor- and oncologist-led organizations played an important role in filling existing gaps in public health care systems through awareness raising, patient support, and advocacy to improve early detection and access to treatment. Barriers to these efforts included persistent stigma, mistrust of patients toward the public health care system, limited access to evidence-based guidelines, difficulty adapting existing best practices to their setting, and insufficient involvement of policymakers. Key facilitators of advocacy efforts included effective local and international partnerships with physicians, like-minded organizations, and policymakers to facilitate access to educational resources, improve breast cancer early detection and care, and catalyze meaningful policy change. CONCLUSION: Our findings highlight the value of providing opportunities for advocates to connect and share experiences. To advance cancer advocacy and improve cancer care, the following needs were identified: dissemination of resource-adapted information for improving outcomes; needs assessments; improved program-monitoring practices; and fostering and promotion of collaboration between advocates, medical professionals, and local governments.

Male sex workers in Moscow, Russia: a pilot study of demographics, substance use patterns, and prevalence of HIV-1 and sexually transmitted infections.

The Russian federation has been undergoing a concentrated epidemic of HIV-1 with high rates of infection among injecting drug users. Less is known about the relative risk and contribution to the country's HIV epidemic by other at-risk populations including sex workers and men who have sex with men. The goals of this project were to explore demographic characteristics, substance use patterns, and estimate the prevalence of sexually transmitted infections (STIs) and high-risk behaviors among male sex workers (MSW) in Moscow and to assess the feasibility of prospective cohort recruitment and retention among this population. Research design was a longitudinal study of 50 men with a six-month follow-up period. Participants were recruited through venue-based and snowball sampling methods. Results revealed an HIV prevalence at baseline of 16%; one MSW seroconverted during the follow-up period, yielding an incidence estimate of 4.8/100PY (95%CI 0.0-11.2). Twenty-four percentage were diagnosed with at least one STI: 12% had syphilis; 8% had Human Papilloma Virus (HPV); and 4% had Herpes Simplex Virus (HSV)-2. Three (6%) of the study participants had evidence of previous Hepatitis C Virus (HCV) exposure at baseline. Retention rates were poor with higher retention significantly associated with older men (OR: 13.1, 95% CI 3.3-52.5). This was the first study to evaluate baseline demographics, substance use patterns, and prevalence of infectious disease among MSW in Moscow. Identification and recruitment of this population appears to be feasible, but retention a challenge. While the sample size in the current study was small, the results also suggested that this is a population at considerable high risk for HIV. MSW in Moscow may be an important at-risk population in the Russian HIV epidemic and further research is urgently required to address their needs and explore prevention strategies.

Patient Advocacy Approaches to Improving Care for Breast and Cervical Cancer in East and Southern Africa.

PURPOSE: Breast and cervical cancer are the most common cancers among women in East and Southern Africa, where mortality remains high because of late diagnosis and limited access to treatment. We explored local approaches to breast and cervical cancer advocacy to identify the most pressing issues and opportunities for increasing the impact of civil society activities in the region. METHODS: Focus group discussions were conducted with participants of the 2016 Women's Empowerment Cancer Advocacy Network (WE CAN) Summit in Nairobi, Kenya. Discussions were audio-recorded, transcribed, coded, and analyzed for emergent themes. Results were presented to participants of 2019 WE CAN summit for cross-validation. RESULTS: Four focus group discussions were conducted with 50 participants. Thirty-six (70%) identified as advocates, 30 (59%) as cancer survivors, 14 (27%) as nongovernmental organization representatives, 13 (25%) as researchers, 4 (8%) as clinicians, and 6 (8%) as policymakers. Although most participants focused on cancer awareness and screening/early detection, some noted that treatment was often unavailable and advocated for a broader strategy to improving access to care. Challenges to designing and implementing such a strategy included knowledge gaps in addressing late diagnosis and access to care, difficulty collaborating with like-minded organizations, approaching policymakers, and addressing treatment financing. Cancer coalitions, although rare, were crucial to building collaborations with ministries of health, policymakers, and international organizations that advanced breast and cervical cancer care. CONCLUSION: Participants indicated that they would benefit from additional training about resource-appropriate best practices for improving breast and cervical cancer care and outcomes. Coalition-building and collaborations, including with oncologists and other medical professionals involved in cancer care, were crucial to leveraging limited resources, sharing lessons learned, and developing local solutions to common challenges.

Treatment default amongst patients with tuberculosis in urban Morocco: predicting and explaining default and post-default sputum smear and drug susceptibility results.

SETTING: Public tuberculosis (TB) clinics in urban Morocco. OBJECTIVE: Explore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance. DESIGN: Case-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals' perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing. RESULTS: 91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one's treatment duration. Age >50 years, never smoking, and having friends who knew one's diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare. CONCLUSION: The causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings.

Phospho-ΔNp63α/microRNA feedback regulation in squamous carcinoma cells upon cisplatin exposure.

Our previous reports showed that the cisplatin exposure induced the ATM-dependent phosphorylation of ΔNp63a, which is subsequently involved in transcriptional regulation of gene promoters encoding mRNAs and microRNAs in squamous cell carcinoma (SCC) cells upon cisplatin-induced cell death. We showed that phosphorylated (p)-ΔNp63a plays a role in upregulation of pro-apoptotic proteins, while non-p-ΔNp63a is implicated in pro-survival signaling. In contrast to non-p-ΔNp63a, p-ΔNp63a modulated expression of specific microRNAs in SCC cells exposed to cisplatin. These microRNAs were shown to attenuate the expression of several proteins involved in cell death/survival, suggesting the critical role for p-ΔNp63a in regulation of tumor cell resistance to cisplatin. Here, we studied the function of ΔNp63a in transcriptional activation and repression of the specific microRNA promoters whose expression is affected by cisplatin treatment of SCC cells. We quantitatively studied chromatin-associated proteins bound to tumor protein (TP) p63-responsive element, we found that p-ΔNp63a along with certain transcription coactivators (e.g., CARM1, KAT2B, TFAP2A, etc.) necessary to induce gene promoters for microRNAs (630 and 885-3p) or with transcription corepressors (e.g., EZH2, CTBP1, HDACs, etc.) needed to repress promoters for microRNAs (181a-5p, 374a-5p and 519a-3p) in SCC cells exposed to cisplatin.