Global burden of oral cancer in 2022 attributable to smokeless tobacco and areca nut consumption: a population attributable fraction analysis.

BACKGROUND: Consuming products that contain smokeless tobacco or areca nut increases the risk of oral cancer. We aimed to estimate the burden of oral cancer attributable to smokeless tobacco or areca nut consumption globally and by type of smokeless tobacco or areca nut product in four major consuming countries. METHODS: We calculated population attributable fractions (PAFs) using prevalence of current use of smokeless tobacco or areca nut products from national surveys and corresponding risks of oral cancer from the literature. We applied PAFs to national estimates of oral cancer incidence in 2022 from the Global Cancer Observatory's Cancer Today database to obtain cases attributable to smokeless tobacco or areca nut consumption. We modelled 95% uncertainty intervals (UIs) using Monte Carlo simulations. FINDINGS: Globally, an estimated 120 200 (95% UI 115 300-124 300) cases of oral cancer diagnosed in 2022 were attributable to smokeless tobacco or areca nut consumption, accounting for 30·8% (95% UI 29·6-31·9) of all oral cancer cases (120 200 of 389 800). An estimated 77% of attributable cases were among male patients (92 600 cases, 95% UI 88 000-96 500) and 23% were among female patients (27 600 cases, 26 000-29 000). Regions with the highest PAFs were Melanesia, Micronesia, and Polynesia (78·6%, 95% UI 74·4-80·5), southcentral Asia (57·5%, 54·8-59·5), and southeastern Asia (19·8%, 19·0-20·6). Lower-middle-income countries represented 90·2% of the world total attributable cases (108 400 cases, 95% UI 103 400-112 200). INTERPRETATION: Our findings suggest that one in three cases of oral cancer globally are attributable to smokeless tobacco or areca nut consumption, and could be prevented through smokeless tobacco and areca nut control. Global cancer control efforts must incorporate further measures to reduce smokeless tobacco and areca nut consumption in populations with the largest attributable burden. FUNDING: French National Cancer Institute.

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Global burden of bladder cancer mortality in 2020 and 2040 according to GLOBOCAN estimates.

INTRODUCTION: In 2020, bladder cancer (BC) was the seventh most prevalent cancer in the world, with 5-year prevalence of more than 1.7 million cases. Due to the main risk factors-smoking and chemical exposures-associated with BC, it is considered a largely preventable and avoidable cancer. An overview of BC mortality can allow an insight not only into the prevalence of global risk factors, but also into the varying efficiency of healthcare systems worldwide. For this purpose, this study analyzes the national mortality estimates for 2020 and projected future trends up to 2040. MATERIALS AND METHODS: Age-standardized mortality rates per 100,000 person-years of BC for 185 countries by sex were obtained from the GLOBOCAN 2020 database, operated by the International Agency for Research on Cancer (IARC). Mortality rates were stratified according to sex and Human Development Index (HDI). BC deaths were projected up to 2040 on the basis of demographic changes, alongside different scenarios of annually increasing, stable or decreasing mortality rates from the baseline year of 2020. RESULTS: In 2020, nearly three times more men died from BC than women, with more than 210,000 deaths in both sexes combined, worldwide. Regardless of gender, more than half of the total BC deaths were from countries with a very high HDI. According to our projections, while the number of deaths for men can only increase up to 54% (from 159 to around 163-245 thousand), for women it is projected to increase two- to three-fold (from 50 to around 119-176 thousand) by 2040. The burden of BC mortality in countries with a very high HDI versus high HDI appears to converge by 2040 for both sexes. CONCLUSION: Opposite mortality trends by gender highlight the urgent need for immediate interventions to expand anti-tobacco strategies, especially for women. The implementation of more strict occupational health and safety regulations could also prevent exposures associated with BC. Improving the ability to detect BC earlier and access to treatment can have a significant positive impact on reducing mortality rates, minimizing economic costs, and enhancing the quality of life for patients.

Correction: Habit Strength, Medication Adherence, and Habit-Based Mobile Health Interventions Across Chronic Medical Conditions: Systematic Review.

[This corrects the article DOI: 10.2196/17883.].

Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo.

The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to identify covalent inhibitors targeting Pin1's active site Cys113, leading to the development of Sulfopin, a nanomolar Pin1 inhibitor. Sulfopin is highly selective, as validated by two independent chemoproteomics methods, achieves potent cellular and in vivo target engagement and phenocopies Pin1 genetic knockout. Pin1 inhibition had only a modest effect on cancer cell line viability. Nevertheless, Sulfopin induced downregulation of c-Myc target genes, reduced tumor progression and conferred survival benefit in murine and zebrafish models of MYCN-driven neuroblastoma, and in a murine model of pancreatic cancer. Our results demonstrate that Sulfopin is a chemical probe suitable for assessment of Pin1-dependent pharmacology in cells and in vivo, and that Pin1 warrants further investigation as a potential cancer drug target.

An Inhibitor of PIDDosome Formation.

The PIDDosome-PIDD-RAIDD-caspase-2 complex-is a proapoptotic caspase-activation platform of elusive significance. DNA damage can initiate complex assembly via ATM phosphorylation of the PIDD death domain (DD), which enables RAIDD recruitment to PIDD. In contrast, the mechanisms limiting PIDDosome formation have remained unclear. We identify the mitotic checkpoint factor BubR1 as a direct PIDDosome inhibitor, acting in a noncanonical role independent of Mad2. Following its phosphorylation by ATM at DNA breaks, "primed" PIDD relocates to kinetochores via a direct interaction with BubR1. BubR1 binds the PIDD DD, competes with RAIDD recruitment, and negates PIDDosome-mediated apoptosis after ionizing radiation. The PIDDosome thus sequentially integrates DNA damage and mitotic checkpoint signals to decide cell fate in response to genotoxic stress. We further show that by sequestering PIDD at the kinetochore, BubR1 acts to delay PIDDosome formation until the next cycle, defining a new mechanism by which cells evade apoptosis during mitosis.

Habit Strength, Medication Adherence, and Habit-Based Mobile Health Interventions Across Chronic Medical Conditions: Systematic Review.

BACKGROUND: Unintentional medication nonadherence is common and has been associated with poor health outcomes and increased health care costs. Earlier research demonstrated a relationship between habit strength and medication adherence. Previous research also examined a habit's direct effect on adherence and how habit interacts with more conscious factors to influence or overrule them. However, the relationship between habit and adherence and the role of habit-based mobile health (mHealth) interventions remain unclear. OBJECTIVE: This review aimed to systematically evaluate the most recent evidence for habit strength, medication adherence, and habit-based mHealth interventions across chronic medical conditions. METHODS: A keyword search with combinations of the terms habit, habit strength, habit index, medication adherence, and medication compliance was conducted on the PubMed database. After duplicates were removed, two authors conducted independent abstract and full-text screening. The guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed when reporting evidence across the included and reviewed studies. RESULTS: Of the 687 records examined, 11 met the predefined inclusion criteria and were finalized for data extraction, grading, and synthesis. Most included studies (6/11, 55%) were cross-sectional and used a theoretical model (8/11, 73%). The majority of studies measured habit strength using the self-report habit index and self-report behavioral automaticity index (9/11, 82%). Habit strength was positively correlated with medication adherence in most studies (10/11, 91%). Habit mediated the effects of self-efficacy on medication adherence (1/11, 9%), and social norms moderated the effects of habit strength on medication adherence (1/11, 9%). Habit strength also moderated the effects of poor mental health symptoms and medication adherence (1/11, 9%). None of the included studies reported on using or proposing a habit-based mHealth behavioral intervention to promote medication adherence. CONCLUSIONS: Habit strength was strongly correlated with medication adherence, and stronger habit was associated with higher medication adherence rates, regardless of the theoretical model and/or guiding framework. Habit-based interventions should be used to increase medication adherence, and these interventions could leverage widely available mobile technology tools such as mobile apps or text messaging, and existing routines.

Health-related quality of life with standard and curative therapies in thalassemia: A narrative literature review.

Health-related quality of life (HRQOL) is a patient-reported outcome that assesses the impact of a disease or illness on different domains of a patient's life. Different general and disease-specific measures can be used to evaluate HRQOL. This article aimed to summarize the evidence for HRQOL among patients with transfusion-dependent (TDT) and non-transfusion-dependent thalassemia (NTDT). We included HRQOL data related to standard therapy with blood transfusions, iron chelation, and/or luspatercept in TDT and NTDT, as well as curative therapies for TDT, including hematopoietic stem cell transplant (HSCT) and gene therapy. Patients with thalassemia had worse HRQOL scores compared to the general population, and chronic pain was seen to increase in frequency and severity over time with age. NTDT patients reported worse physical health and functioning, mental health, general health, and vitality than TDT patients. However, TDT patients reported worse pain, change in health, and social support than NTDT. Most therapies improved overall HRQOL among thalassemia patients. Deferasirox, an oral iron chelator, was associated with more HRQOL benefits compared to deferoxamine, an intravenous iron chelator. Luspatercept showed clinically meaningful improvement in physical functioning among TDT and NTDT. Furthermore, HSCT and gene therapy were associated with better physical, emotional, and mental domains scores.

Gaps in Migrants' Access to Contraceptive Services: A Survey of Nepalese Women and Men in Japan.

While all modern contraceptive methods are available for free or at minimal cost in Nepal, contraceptive devices in Japan are mainly limited to condoms, requiring Nepalese migrant women to rely on their male partners for their use. Therefore, Nepalese migrants often seek contraceptive devices from Nepal or request friends or relatives to send them from their home country. This study aimed to identify the gaps and challenges associated with Nepalese migrants' needs for sexual and reproductive health services (SRHSs), particularly contraceptives, before and after their migration to Japan. A mixed-methods study was adopted, an explanatory sequential design (ESD) combining quantitative and qualitative approaches, and data were collected from 186 Nepalese migrants (80 females and 106 males) through an online survey and from two focus-group discussions (FGDs) conducted among 24 participants (14 females and 10 males). This study highlighted the obstacles faced by Nepalese migrants in accessing contraceptive services, such as limited options, language barriers, and high costs. The study also revealed the importance of pre-departure training in Nepal and organizing post-arrival training in Japan to increase Nepalese migrants' awareness of the SRHSs available in Japan, thereby helping to prevent SRH-related health problems, including unintended pregnancies and abortions, in Japan.

Stepwise phosphorylation and SUMOylation of PIDD1 drive PIDDosome assembly in response to DNA repair failure.

SUMOylation regulates numerous cellular stress responses, yet targets in the apoptotic machinery remain elusive. We show that a single, DNA damage-induced monoSUMOylation event controls PIDDosome (PIDD1/RAIDD/caspase-2) formation and apoptotic death in response to unresolved DNA interstrand crosslinks (ICLs). SUMO-1 conjugation occurs on conserved K879 in the PIDD1 death domain (DD); is catalyzed by PIAS1 and countered by SENP3; and is triggered by ATR phosphorylation of neighboring T788 in the PIDD1 DD, which enables PIAS1 docking. Phospho/SUMO-PIDD1 proteins are captured by nucleolar RAIDD monomers via a SUMO-interacting motif (SIM) in the RAIDD DD, thus compartmentalizing nascent PIDDosomes for caspase-2 recruitment. Denying SUMOylation or the SUMO-SIM interaction spares the onset of PIDDosome assembly but blocks its completion, thus eliminating the apoptotic response to ICL repair failure. Conversely, removal of SENP3 forces apoptosis, even in cells with tolerable ICL levels. SUMO-mediated PIDDosome control is also seen in response to DNA breaks but not supernumerary centrosomes. These results illuminate PIDDosome formation in space and time and identify a direct role for SUMOylation in the assembly of a major pro-apoptotic device.

Real-world use of inotuzumab ozogamicin is associated with lower health care costs than blinatumomab in patients with acute lymphoblastic leukemia in the first relapsed/refractory setting.

Aim: To compare all-cause and acute lymphoblastic leukemia (ALL)-related healthcare resource utilization (HCRU) and costs among patients receiving inotuzumab ozogamicin (InO) and blinatumomab (Blina) for ALL in the first relapsed/refractory (R/R) setting. Patients & methods: We studied retrospective claims for adult commercial and Medicare Advantage enrollees with ALL receiving InO (n = 29) or Blina (n = 23) from 1 January 2015 to 16 February 2021. Mean per-patient-per-month (PPPM) HCRU and total costs were described and multivariable-adjusted PPPM total all-cause and ALL-related predicted costs were calculated. Results: Mean monthly ALL-related hospitalizations were the same for patients receiving InO and Blina (PPPM = 0.8 stays); however, the length of ALL-related hospital stay was almost twice as long among patients receiving Blina versus InO (ALL-related: InO = 7.6 days; Blina = 14.1 days; p = 0.346). In multivariable models, total ALL-related costs were 43% lower for InO compared with Blina (PPPM costs: InO = $93,767; Blina = $163,470; p = 0.021). Conclusion: In the first R/R setting, patients who used InO had significantly lower all-cause and ALL-related costs compared with patients who used Blina, in part driven by hospitalization patterns.

Disparities and Determinants of Testing for Early Detection of Cervical Cancer among Nepalese Women: Evidence from a Population-Based Survey.

BACKGROUND: Cervical cancer presents a considerable challenge in South Asia, notably in Nepal, where screening remains limited. Past research in Nepal lacked national representation and a thorough exploration of factors influencing cervical cancer screening, such as educational and socioeconomic disparities. This study aims to measure these gaps and identify associated factors in testing for early detection of cervical cancer among Nepalese women. METHODS: Data from the 2019 Nepal Noncommunicable Disease Risk Factors survey (World Health Organization STEPwise approach to noncommunicable risk factor surveillance), involving 2,332 women aged 30 to 69 years, were used. Respondents were asked if they had undergone cervical cancer testing through visual inspection with acetic acid, Pap smear, or human papillomavirus test ever or in the past 5 years. The slope index of inequality (SII) and relative concentration index were used to measure socioeconomic and education-based disparities in cervical cancer test uptake. RESULTS: Only 7.1% [95% confidence interval (CI): 5.1-9.9] Nepalese women had ever undergone cervical cancer testing, whereas 5.1% (95% CI: 3.4-7.5) tested within the last 5 years. The ever uptake of cervical cancer testing was 5.1 percentage points higher (SII: 5.1, 95% CI: -0.1 to 10.2) among women from the richest compared with the poorest households. Education-based disparities were particularly pronounced, with a 13.9 percentage point difference between highly educated urban residents and their uneducated counterparts (SII: 13.9, 95% CI: 5.8-21.9). CONCLUSIONS: Less than one in ten women in Nepal had a cervical cancer testing, primarily favoring higher educated and wealthier individuals. IMPACT: Targeted early detection and cervical cancer screening interventions are necessary to address these disparities and improve access and uptake.

Global Stage Distribution of Breast Cancer at Diagnosis: A Systematic Review and Meta-Analysis.

Importance: Stage at diagnosis is a key prognostic factor for cancer survival. Objective: To assess the global distribution of breast cancer stage by country, age group, calendar period, and socioeconomic status using population-based data. Data Sources: A systematic search of MEDLINE and Web of Science databases and registry websites and gray literature was conducted for articles or reports published between January 1, 2000, and June 20, 2022. Study Selection: Reports on stage at diagnosis for individuals with primary breast cancer (C50) from a population-based cancer registry were included. Data Extraction and Synthesis: Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers (J.D.B.F., A.D.A., A.M., R.S., and F.G.). Stage-specific proportions were extracted and cancer registry data quality and risk of bias were assessed. National pooled estimates were calculated for subnational or annual data sets using a hierarchical rule of the most relevant and high-quality data to avoid duplicates. Main Outcomes and Measures: The proportion of women with breast cancer by (TNM Classification of Malignant Tumors or the Surveillance, Epidemiology, and End Results Program [SEER]) stage group. Results: Data were available for 2.4 million women with breast cancer from 81 countries. Globally, the proportion of cases with distant metastatic breast cancer at diagnosis was high in sub-Saharan Africa, ranging from 5.6% to 30.6% and low in North America ranging from 0.0% to 6.0%. The proportion of patients diagnosed with distant metastatic disease decreased over the past 2 decades from around 3.8% to 35.8% (early 2000s) to 3.2% to 11.6% (2015 onwards), yet stabilization or slight increases were also observed. Older age and lower socioeconomic status had the largest proportion of cases diagnosed with distant metastatic stage ranging from 2.0% to 15.7% among the younger to 4.1% to 33.9% among the oldest age group, and from 1.7% to 8.3% in the least disadvantaged groups to 2.8% to 11.4% in the most disadvantaged groups. Conclusions and Relevance: Effective policy and interventions have resulted in decreased proportions of women diagnosed with metastatic breast cancer at diagnosis in high-income countries, yet inequality persists, which needs to be addressed through increased awareness of breast cancer symptoms and early detection. Improving global coverage and quality of population-based cancer registries, including the collection of standardized stage data, is key to monitoring progress.

Global review of COVID-19 mitigation strategies and their impact on cancer service disruptions.

During the COVID-19 pandemic, countries adopted mitigation strategies to reduce disruptions to cancer services. We reviewed their implementation across health system functions and their impact on cancer diagnosis and care during the pandemic. A systematic search was performed using terms related to cancer and COVID-19. Included studies reported on individuals with cancer or cancer care services, focusing on strategies/programs aimed to reduce delays and disruptions. Extracted data were grouped into four functions (governance, financing, service delivery, and resource generation) and sub-functions of the health system performance assessment framework. We included 30 studies from 16 countries involving 192,233 patients with cancer. Multiple mitigation approaches were implemented, predominantly affecting sub-functions of service delivery to control COVID-19 infection via the suspension of non-urgent cancer care, modified treatment guidelines, and increased telemedicine use in routine cancer care delivery. Resource generation was mainly ensured through adequate workforce supply. However, less emphasis on monitoring or assessing the effectiveness and financing of these strategies was observed. Seventeen studies suggested improved service uptake after mitigation implementation, yet the resulting impact on cancer diagnosis and care has not been established. This review emphasizes the importance of developing effective mitigation strategies across all health system (sub)functions to minimize cancer care service disruptions during crises. Deficiencies were observed in health service delivery (to ensure equity), governance (to monitor and evaluate the implementation of mitigation strategies), and financing. In the wake of future emergencies, implementation research studies that include pre-prepared protocols will be essential to assess mitigation impact across cancer care services.

An evaluation of deferiprone as twice-a-day tablets or in combination therapy for the treatment of transfusional iron overload in thalassemia syndromes.

INTRODUCTION: Regular blood transfusions in patients with thalassemia syndromes can cause iron overload resulting in complications including cirrhosis, heart problems, or endocrine abnormalities. To prevent iron overload toxicity in these patients, three iron chelators are currently FDA-approved for use: deferoxamine, deferasirox, and deferiprone. In the United States, deferiprone has been approved for three times daily dosing since 2011 and has recently gained approval for twice-daily administration. AREAS COVERED: A PubMed literature search was performed with the keywords 'deferiprone' and 'thalassemia.' Relevant original research studying deferiprone's effects on transfusional iron overload in patients with thalassemia syndromes was included. Exclusion criteria included case reports and review papers. Deferiprone is effective at reducing serum ferritin levels in patients with iron overload. Twice-daily administration provides a similar level of iron chelation as three times daily dosing with a comparable side effect profile and increased patient acceptability. EXPERT OPINION: New studies are highlighting deferiprone's potential for combination therapy with either deferoxamine or deferasirox to improve iron chelation. Deferiprone's ability to significantly decrease cardiac and liver iron content can be utilized in other transfusion-dependent hematologic conditions, as evidenced by its recent approval for use in the United States for sickle cell disease or other anemias.

Effect of COVID-19 pandemic on internet gaming disorder among general population: A systematic review and meta-analysis.

Internet gaming disorder (IGD) has been rising in recent years. The COVID-19 pandemic has led to a noticeable shift in the way people interact with technology, which could have further contributed to an increase in IGD. Post-pandemic, the concern for IGD is likely to continue as people have become increasingly reliant on online activities. Our study aimed to assess the prevalence of IGD among the general population globally during the pandemic. Relevant studies that assessed IGD during COVID-19 were identified using PubMed, EMBASE, Scopus, CINAHL, and PsycNET between 2020, Jan 1 and 2022, May 23. We used NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to assess the risk of bias, and GRADEpro for the certainty of the evidence. Three separate meta-analyses were performed using Comprehensive meta-analysis software and Revman 5.4. In total, 362 studies were identified, of which 24 observational (15 cross-sectional and 9 longitudinal) studies among 83,903 population were included in the review, and 9 studies in the meta-analysis. The risk of bias assessment showed an overall fair impression among the studies. The meta-analysis for a single group of 3 studies showed the prevalence rate of 8.00% for IGD. Another meta-analysis of 4 studies for a single group showed a pooled mean of 16.57 which was lower than the cut-off value of the IGDS9-SF tool. The two-group meta-analysis of 2 studies showed no significant difference between the groups before and during COVID-19. Our study showed no clear evidence of increased IGD during COVID-19 due to limited number of comparable studies, substantial heterogeneity, and low certainty of evidence. Further well-designed studies are needed to provide stronger evidence to implement suitable interventions to address IGD worldwide. The protocol was registered and published in the International Prospective Register for Systematic Review (PROSPERO) with the registration number CRD42021282825.

How positive deviants helped in fighting the early phase of COVID-19 pandemic? A qualitative study exploring the roles of frontline health workers in Nepal.

Positive deviance is an approach wherein learnings from persons who fare better than their peers under similar circumstances are used to enable behavioral and social change. Such behaviors and solutions are likely affordable, acceptable, sustainable, and fit into the socio-cultural milieu. Despite the wide use of positive deviance in many public health programs and research, it has yet to be used to study frontline workers in the context of COVID-19. Therefore, this study aimed to explore the positive deviance traits among frontline health workers during the early days of the COVID-19 pandemic in Nepal. This qualitative study followed a grounded theory approach. The data was collected through in-depth interviews among the 17 identified participants representing different cadres of the health workforce, types of health facilities, and regions across Nepal purposively. The findings are structured around four major themes: challenges, finding solutions and innovations, positive lessons, and motivations. The personal challenges included fear and anxiety about the uncertainties. The professional challenges included stigma, infection control, and changing work style with the use of personal protective equipment. Despite the challenges, they managed available resources and innovated low-cost, technological, and practice-based solutions. They were able to reflect upon the positive lessons learned, such as self-sustainability, teamwork, and policy direction and research, and self-reflection of personal growth and patient care. The intrinsic motivation included their inherent value system, and the extrinsic motivation included appreciation and acknowledgment, family and social support, psychosocial support from peers, and support from higher authorities. This study provides insights into how the positive deviance approach can help identify the solution amid the most challenging circumstances, such as the COVID-19 pandemic in low-resource settings. However, more extensive studies are warranted to explore deeper into positive deviance and its long-term effects in bringing positive outcomes during the pandemic.

The Patient Experience of Acute Lymphoblastic Leukemia and Its Treatment: Social Media Review.

BACKGROUND: Adult patients with acute lymphoblastic leukemia (ALL) report substantial disease- and treatment-related impacts on their health-related quality of life (HRQOL). Patient-reported information (PRI) shared on social media may provide a distinct opportunity to understand the patient experience outside of formal research contexts and help inform the development of novel therapies. OBJECTIVE: This qualitative social media review aimed to assess PRI shared on social media websites to gain a better understanding of the symptom, HRQOL, and treatment impacts on individuals with ALL. METHODS: We identified English-language posts on 3 patient advocacy websites (Patient Power, The Patient Story, and Leukaemia Care) and YouTube that included PRI about experiences with ALL or ALL treatments shared by adults (aged ≥18 years) with a self-reported ALL diagnosis. Patients' demographic and disease characteristics were extracted from posts (where available), and the posts were analyzed thematically. A network analysis was conducted to delineate possible associations among ALL symptoms, HRQOL impacts, and treatment-related symptoms and impacts. RESULTS: Of the 935 social media posts identified, 63 (7%) met the review criteria, including 40 (63%) videos, 5 (8%) comments posted in response to videos, and 18 (29%) blog posts. The 63 posts were contributed by 41 patients comprised of 21 (51%) males, 18 females (44%), and 2 (5%) whose gender was not reported. Among the patients, 13 (32%) contributed >1 source of data. Fatigue (n=20, 49%), shortness of breath (n=13, 32%), and bruising (n=12, 29%) were the symptoms prior to treatment most frequently discussed by patients. Patients also reported impacts on personal relationships (n=26, 63%), psychological and emotional well-being (n=25, 61%), and work (n=16, 39%). Although inpatient treatment reportedly restricted patients' independence and social functioning, it also provided a few patients with a sense of safety. Patients frequently relied on their doctors to drive their treatment decisions but were also influenced by family members. The network analysis indicated that disease-related symptoms were primarily associated with patients' physical functioning, activities of daily living, and ability to work, while treatment-related symptoms were primarily associated with emotional well-being. CONCLUSIONS: This social media review explored PRI through a thematic analysis of patient-contributed content on patient advocacy websites and YouTube to identify and contextualize emergent themes in patient experiences with ALL and its treatments. To our knowledge, this is the first study to leverage this novel tool to generate new insights into patients' experiences with ALL. Patients' social media posts suggest that inpatient care for ALL is associated with restricted independence and social functioning. However, inpatient care also provided a sense of safety for some patients. Studies such as this one that capture patients' experiences in their own words are valuable tools to further our knowledge of patient outcomes with ALL.

Outcomes with high dose cytarabine and mitoxantrone induction for adults with mixed phenotype acute leukemia.

The optimal induction strategy for mixed phenotype acute leukemia (MPAL) is unknown, though retrospective data has shown improved remission rates and overall survival with acute lymphoblastic leukemia (ALL)-based regimens. At Memorial Sloan Kettering Cancer Center (MSKCC), the most utilized induction regimen for MPAL is high dose cytarabine plus mitoxantrone ("ALL-2"), though outcomes with this regimen are not well described. In this study, outcomes to first-line induction chemotherapy in 24 patients at MSKCC with MPAL classified by 2016 World Health Organization criteria are reported. The overall response rate was 94 % (16 of 17) in patients receiving ALL-2, including 86 % (6 of 7) in patients with extramedullary disease. Thirteen patients who received ALL-2 induction proceeded to allogeneic hematopoietic cell transplant (allo-HCT). The most common toxicity associated with ALL-2 was febrile neutropenia, documented in 12 patients. With a median follow-up of 37 months, median overall survival was not reached in the ALL-2 cohort, and 3-year overall survival was 62 %. In multivariate analysis, age ≥ 60 years and MPAL with isolated extramedullary disease were associated with significantly worse overall survival (P = .009 and P = .01, respectively). These results support further prospective investigation of ALL-2 as a front-line induction regimen for adults with MPAL.

Correction: The Patient Experience of Acute Lymphoblastic Leukemia and Its Treatment: Social Media Review.

[This corrects the article DOI: 10.2196/39852.].