The interaction between social determinants of health and cervical cancer survival: A systematic review.

OBJECTIVE: This systematic review aimed to investigate what are the most relevant social determinants of health (SDH), how they are measured, how they interact among themselves and what is their impact on the outcomes of cervical cancer patients. METHODS: Search was performed in PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar databases from January 2001 to September 2022. The protocol was registered at PROSPERO (CRD42022346854). We followed the PICOS strategy: Population- Patients treated for cervical cancer in the United States; Intervention - Any SDH; Comparison- None; Outcome measures- Cancer treatment outcomes related to the survival of the patients; Types of studies- Observational studies. Two reviewers extracted the data following the PRISMA guidelines. Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used for risk of bias (ROB) assessment. RESULTS: Twenty-four studies were included (22 had low and 2 had moderate ROB). Most manuscripts analyzed data from public registries (83.3%) and only one SDH (54.17%). The SDH category of Neighborhood was not included in any study. Although the SDH were measured differently across the studies, not being married, receiving treatment at a low-volume hospital, and having public insurance (Medicaid or Medicare) or not being insured was associated with shorter survival of cervical cancer patients in most studies. CONCLUSIONS: There is a deficit in the number of studies comprehensively assessing the impact of SDH on cervical cancer treatment-related outcomes. Marital status, hospital volume and health insurance status are potential predictors of worse outcome.

Estimated Savings After Stopping Tyrosine Kinase Inhibitor Treatment Among Patients With Chronic Myeloid Leukemia.

Importance: Patients with chronic myeloid leukemia (CML) who have a sustained deep molecular response using tyrosine kinase inhibitors (TKIs) can safely attempt to stop their use. As these medications are very costly, this change in treatment protocols may result in large savings. Objective: To estimate future savings from attempting to stop TKI use among patients with CML who have deep molecular response. Design, Setting, and Participants: A microsimulation model was developed for this decision analytical modeling study to estimate costs for US adults moving from using a TKI, to attempting discontinuation and then reinitiating TKI therapy, if clinically appropriate. Estimates were calculated for US patients who currently have CML and simulated newly diagnosed cohorts of patients over the next 30 years. Exposure: Attempting to stop using a TKI. Main Outcomes and Measures: Estimated savings after attempted discontinuation of TKI use. Results: A simulated population of individuals with CML in 2018 and future populations were created using estimates from the SEER*Explorer website. The median age at diagnosis was 66 years for men and 65 years for women. Between 2022 and 2052, the savings associated with eligible patients attempting discontinuation of TKI therapy was estimated at more than $30 billion among those currently diagnosed and over $15 billion among those who will develop CML in the future, for a total savings of over $54 billion by 2052 for drug treatment and polymerase chain reaction testing. The estimate is conservative as it does not account for complications and other health care-associated costs for patients continuing TKI therapy. Conclusions and Relevance: The findings of this decision analytical modeling study of patients with CML suggest that attempting discontinuation of TKI therapy could save over $54 billion during the next 30 years. Further education for patients and physicians is needed to safely increase the number of patients who can successfully attain treatment-free remission.

Disparities in survival of hematologic malignancies in the context of social determinants of health: a systematic review.

Social determinants of health (SDHs) have been reported as relevant factors responsible for health inequity. We sought to assess clinical data from observational studies conducted in the United States evaluating the impact of SDHs on the outcomes of patients with hematologic malignancies. Thus, we performed a systematic review in 6 databases on 1 September 2021, in which paired reviewers independently screened studies and included data from 41 studies. We assessed the risk of bias using the Joanna Briggs Institute appraisal tools and analyzed the data using a descriptive synthesis. The most common SDH domains explored were health care access and quality (54.3%) and economic stability (25.6%); others investigated were education (19%) and social and community context (7.8%). We identified strong evidence of 5 variables significantly affecting survival: lack of health insurance coverage or having Medicare or Medicaid insurance, receiving cancer treatment at a nonacademic facility, low household income, low education level, and being unmarried. In contrast, the reports on the effect of distance traveled to the treatment center are contradictory. Other SDHs examined were facility volume, provider expertise, poverty, and employment rates. We identified a lack of data in the literature in terms of transportation, debt, higher education, diet, social integration, environmental factors, or stress. Our results underscore the complex nature of social, financial, and health care barriers as intercorrelated variables. Therefore, the management of hematologic malignancies needs concerted efforts to incorporate SDHs into clinical care, research, and public health policies, identifying and addressing the barriers at a patient-based level to enhance outcome equity (PROSPERO CRD42022346854).

Health care resource utilization in 3L + patients with chronic phase chronic myeloid leukemia receiving asciminib or bosutinib.

OBJECTIVES: To assess and compare health care resource utilization (HCRU) rates of asciminib and bosutinib at the Week 24, Week 48, and Week 96 cutoffs among 3 L + patients with chronic myeloid leukemia in chronic phase (CML-CP) in the randomized ASCEMBL trial. METHODS: Patients in the ASCEMBL trial (Clinicaltrials.gov: NCT03106779) were randomized to receive asciminib 40 mg twice daily (n = 157) or bosutinib 500 mg once daily (n = 76). At each scheduled visit, investigators conducted HCRU assessment on hospitalization, emergency room visit, general practitioner visit, specialist visit and urgent care visit; duration and type of hospitalization for the hospitalized patients; and reasons for HCRU. The number of patients with HCRU, rate of HCRU per patient-year, and length of hospital stay by ward type were compared at Week 24, Week 48, and Week 96 analyses. RESULTS: Lower proportions of patients receiving asciminib versus bosutinib used any resources including hospitalizations, emergency room visits, general practitioner visits, specialist visits, and urgent care visits (23.6% versus 36.8%, 26.1% versus 39.5%, and 28.6% versus 42.6% at Week 24, Week 48, and Week 96 analyses, respectively). After normalizing for treatment exposure, rates of HCRU for any resource per patient-year were significantly lower for asciminib versus bosutinib: 0.25 (95% CI: 0.18-0.34) versus 0.80 (95% CI: 0.55-1.16) at the Week 24 analysis, 0.20 (95% CI: 0.15-0.27) versus 0.47 (95% CI: 0.32-0.66) at the Week 48 analysis, and 0.17 (95% CI: 0.12-0.22) versus 0.40 (95% CI: 0.27-0.55) at the Week 96 analysis. Among the hospitalized patients, mean length of hospital stay was lower for asciminib than bosutinib for most wards at all three timepoints. CONCLUSIONS: In the ASCEMBL trial, asciminib-treated patients with CML-CP in 3 L + maintained lower resource utilization compared to bosutinib over the long-term.

Ex situ culture of coral species Porites lobata (Scleractinia: Poritidae) and Pocillopora damicornis (Scleractinia: Pocilloporidae), Costa Rica: first assessment and implications

Introduction: Coral reefs worldwide decline has prompted coral restoration as a viable strategy to rewild vulnerable, foundational coral species. Stony corals are now propagated by thousands in both in-water and ex situ (land-based) coral nurseries, the latter being unexplored in Costa Rica, despite their potential benefits as a reef management tool. Objective: To analyze the viability of ex situ culturing of the Pacific reef-building corals Porites lobata and Pocillopora damicornis at Parque Marino del Pacífico (PMP), Puntarenas, Costa Rica, aquaculture facilities. Methods: From May to October 2018 a total of 180 coral fragments were kept in an aquaculture recirculated system. Survival, growth, and fragment yield in relation to culture medium (physicochemical parameters) were recorded. Results: Survival and growth rate varied between species and culture tanks. On average, surviving P. lobata fragments (68.89 %) placed in Tank 1 (T1) grew 216 %, while fragments placed in Tank 2 (T2) had a survival rate of 71.11 % and an increase of 277 % in live tissue area. P. damicornis fragments survival, basal and crown area percentage increase were: 71.11 %, 980 % and 366 % in T1, and 100 %, 976 % and 287 % in T2. Although fragments survival and growth were net positive, the yield in terms of culture was low, due to culture conditions in the tanks not meeting coral culture optimal requirements. Conclusions: Survival and growth of both species varied depending on the tank in which they were placed. Survival was similar to that found in other ex situ studies and growth was similar to those reported in the wild, however culture performance in terms of yield was low. Aquaculture systems at PMP constitute a good base for the cultivation of corals, however for the culture effort to achieve maximum yield, current systems must be optimized according to the requirements of the target coral species.

Introducción: El declive mundial de los arrecifes de coral, ha impulsado a la restauración coralina como una estrategia viable para recuperar especies de coral fundacionales, en estado vulnerable. Los corales pétreos se propagan por miles, tanto en viveros subacuáticos como ex situ (en tierra). Siendo el segundo método poco explorado en Costa Rica, a pesar de sus potenciales beneficios como medida como herramienta de manejo arrecifal. Objetivo: Analizar la viabilidad del cultivo ex situ de las especies de coral constructoras de arrecifes Porites lobata y Pocillopora damicornis en el módulo de acuicultura del Parque Marino del Pacífico (PMP), Puntarenas, Costa Rica. Métodos: Desde el 17 de mayo hasta el 17 de octubre de 2018, se mantuvieron un total de 180 fragmentos de coral en un sistema de recirculación de acuicultura. Se registraron la supervivencia, el crecimiento y el rendimiento de los fragmentos en relación con el medio de cultivo (parámetros fisicoquímicos). Resultados: La tasa de supervivencia y crecimiento varió entre especies y tanques de cultivo. En promedio, los fragmentos de P. lobata supervivientes (68.89 %) colocados en el tanque 1 (T1) crecieron un 216 %. En contraste con los fragmentos colocados en el tanque 2 (T2) que mostraron una tasa de supervivencia del 71.11 % y un aumento del 277 % en el área de tejido vivo. En el caso de P. damicornis, los porcentajes de supervivencia, de aumento del área basal y del área de la corona fueron: 71.11 %, 980 %, y 366 %, y 100 %, 976 %, y 287 % para los fragmentos colocados en T1 y T2, respectivamente. Aunque la supervivencia y el crecimiento de los fragmentos fueron positivos, el rendimiento en términos de cultivo fue bajo, debido a que las condiciones en los tanques no cumplían con las condiciones ideales para el cultivo de corales. Conclusiones: La supervivencia y el crecimiento de ambas especies variaron en función del tanque en el que se colocaron. La supervivencia fue similar a la observada en otros estudios ex situ y el crecimiento fue similar al reportado en la naturaleza, pero el rendimiento del cultivo fue bajo. Los sistemas de acuicultura del PMP constituyen una buena base para el cultivo de corales, sin embargo, para que el esfuerzo de cultivo alcance un máximo de rendimiento, los sistemas actuales deben optimizarse en función de los requisitos de las especies de coral objetivo.

Social needs and health-related quality of life among hematologic cancer survivors.

OBJECTIVES: Recent studies have examined social needs (social determinants of health) among cancer survivors, but studies have not specifically focused on patients with leukemia or lymphoma. We examined food insecurity and other social needs among hematologic cancer survivors, including individuals who had completed primary therapy for leukemia, lymphoma, or multiple myeloma. A particular focus of the study was on the relationship between social needs and health-related quality of life. METHODS: We conducted a postal survey of a multiethnic cohort of hematologic cancer survivors who reside in Augusta, GA, or the surrounding area and who had been treated at the Georgia Cancer Center. RESULTS: A total of 53 patients with a history of hematologic cancer (leukemia, lymphoma, or multiple myeloma) completed the survey (10.6% response rate). The mean age was 62.6 years. The participants were diverse according to annual household income and employment status. About two-thirds were white and almost one-third were African American. Five of 52 participants (9.6%) experienced food insecurity. Patients with food insecurity had poorer HRQOL compared with those who were food secure (63.3 vs. 87.33, p = 0.0308). A similar pattern was seen for those who had difficulty paying utility bills, those who had housing insecurity, and those who had to go without health care because of a lack of transportation. Overall, there was a statistically significant inverse association between HRQOL and number of social needs (p = 0.004). CONCLUSION: When caring for cancer survivors, social needs such as food insecurity and housing insecurity are important considerations for oncologists and primary care providers, especially when caring for patients with lower socioeconomic status and racial/ethnic minorities.

Disease burden and vaccination priorities in Colombia.

INTRODUCTION: In the context of the COVID-19 pandemic, vaccination is considered a potentially effective strategy for controlling the disease. The objective of this study is to estimate the number of people with a high risk of morbidity and those who should be prioritized in immunization planning in Colombia. MATERIALS AND METHODS: The population at risk by age was identified from the national census data of 2018. Various sources were identified to obtain information on the number of patients with different comorbidities, including heart failure, diabetes, chronic kidney failure, cancers, HIV infection, and obesity. Sources were also identified to estimate the number of health workers, teachers and military and police force personnel. RESULTS: By 2021, Colombia is estimated to have a total of 51,049,498 inhabitants, of whom 14% will be people over 60 years of age. Additionally, of the people with comorbidities younger than 60 years old, 5,233,241 inhabitants are expected to be obese, 592,726 are expected to have diabetes mellitus, 216,389 are expected to have chronic kidney disease, and 521,263 are expected to have heart failure, totaling 15,055,697 individuals. Combining the high-priority groups and health workers, a projected 20 million people will have mortality risk factors. CONCLUSIONS: For Colombia's vaccination strategy to have an impact on reducing mortality, population groups with risk factors, corresponding to approximately 15 million inhabitants, as well as essential workers should be prioritized.

Financial assistance programs for cancer patients.

BACKGROUND: The high costs of oncology care can lead to financial stress and have deleterious effects on the well-being of patients and their families. However, only a handful of financial assistance programs for cancer patients have been implemented and evaluated to date. RECENT FINDINGS: Key features of reported programs include instrumental support through financial navigation or education for patients, and financial or charitable support for healthcare costs. Only one of the programs successfully reduced actual out-of-pocket costs for patients, though others were associated with psychosocial benefits or increased knowledge of financial resources. Four of the 5 programs evaluated to date were pilot studies with small sample sizes, and most lack control groups for comparison. CONCLUSIONS: Additional studies are needed that include larger sample sizes and with comparison groups of cancer patients in order to determine whether the counseling and navigator programs are effective in addressing financial distress in this patient population. Of particular interest are programs designed for low-income patients and those who lack health care insurance. Financial assistance programs that implement solutions at different levels of the healthcare system (individual patients, providers, healthcare institutions) are more likely to be effective. Multi-level interventions are needed that address the systems in which patients access care, the actual costs of services and drugs, and the individual needs of patients in order to reduce financial hardship for cancer patients.

Health care access and utilization among adult cancer survivors: Results from the National Institutes of Health "All of Us" Research Program.

BACKGROUND: Many cancer survivors face financial difficulties that prevent them from receiving appropriate health care. Racial/ethnic disparities in receipt of health care have been reported among cancer survivors, but recent data for important racial/ethnic subgroups of the US population are lacking. METHODS: To learn more about barriers to healthcare access faced by cancer survivors, we analyzed data from the NIH "All of Us" Research Program. Data were analyzed about demographic factors and other personal characteristics, personal medical history of cancer, healthcare utilization, and access to care. RESULTS: As of November 2020, a total of 5426 participants had a history of cancer (excluding skin cancer). About 88.2% were non-Hispanic White; 3.9% were Black, African American, or African; 1.3% were Asian; 4.1% were Hispanic, Latino, or Spanish; and 1.2% reported more than one race. Just over one-half had an annual income of $75,000 or greater. The majority of the participants (71.7%) were college graduates or had an advanced degree. About 47.0%% had private health insurance, 41.0% had Medicare, 6.0% had Medicaid, and the remainder had military, Veterans Affairs, other insurance, or no health insurance. Frequently cited reasons for delayed care in the past 12 months were "had to pay out of pocket for some or all of the procedures," "deductible was too high/or could not afford the deductible," "couldn't afford the copay," "couldn't get time off work," and "were nervous about seeing a health care provider." DISCUSSION: A minority of cancer survivors who participated in the NIH "All of Us" Program had difficulty paying for health care in the past 12 months. Of particular concern are minorities such as African American and Hispanic cancer survivors along with those who are low income.

Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial.

IMPORTANCE: Tyrosine kinase inhibitors (TKIs) have been associated with improved survival of patients with chronic myeloid leukemia (CML) but are also associated with adverse effects, especially fatigue and diarrhea. Discontinuation of TKIs is safe and is associated with the successful achievement of treatment-free remission (TFR) for some patients. OBJECTIVE: To evaluate molecular recurrence (MRec) and patient-reported outcomes (PROs) after TKI discontinuation for US patients with CML. DESIGN, SETTING, AND PARTICIPANTS: The Life After Stopping TKIs (LAST) study was a prospective single-group nonrandomized clinical trial that enrolled 172 patients from 14 US academic medical centers from December 18, 2014, to December 12, 2016, with a minimum follow-up of 3 years. Participants were adults with chronic-phase CML whose disease was well controlled with imatinib, dasatinib, nilotinib, or bosutinib. Statistical analysis was performed from August 13, 2019, to March 23, 2020. INTERVENTION: Discontinuation of TKIs. MAIN OUTCOMES AND MEASURES: Molecular recurrence, defined as loss of major molecular response (BCR-ABL1 International Scale ratio >0.1%) by central laboratory testing, and PROs (Patient-Reported Outcomes Measurement Information System computerized adaptive tests) were monitored. Droplet digital polymerase chain reaction (ddPCR) was performed on samples with undetectable BCR-ABL1 by standard real-time quantitative polymerase chain reaction (RQ-PCR). RESULTS: Of 172 patients, 89 were women (51.7%), and the median age was 60 years (range, 21-86 years). Of 171 patients evaluable for molecular analysis, 112 (65.5%) stayed in major molecular response, and 104 (60.8%) achieved TFR. Undetectable BCR-ABL1 by either ddPCR or RQ-PCR at the time of TKI discontinuation (hazard ratio, 3.60; 95% CI, 1.99-6.50; P < .001) and at 3 months (hazard ratio, 5.86; 95% CI, 3.07-11.1; P < .001) was independently associated with MRec. Molecular recurrence for patients with detectable BCR-ABL1 by RQ-PCR was 50.0% (14 of 28), undetectable BCR-ABL1 by RQ-PCR but detectable by ddPCR was 64.3% (36 of 56), and undetectable BCR-ABL1 by both ddPCR and RQ-PCR was 10.3% (9 of 87) (P ≤ .001). Of the 112 patients in TFR at 12 months, 90 (80.4%) had a clinically meaningful improvement in fatigue, 39 (34.8%) had a clinically meaningful improvement in depression, 98 (87.5%) had a clinically meaningful improvement in diarrhea, 24 (21.4%) had a clinically meaningful improvement in sleep disturbance, and 5 (4.5%) had a clinically meaningful improvement in pain interference. Restarting a TKI resulted in worsening of PROs. CONCLUSIONS AND RELEVANCE: In this study, TKI discontinuation was safe, and 60.8% of patients remained in TFR. Discontinuation of TKIs was associated with improvements in PROs. These findings should assist patients and physicians in their decision-making regarding discontinuation of TKIs. Detectable BCR-ABL1 by RQ-PCR or ddPCR at the time of TKI discontinuation was associated with higher risk of MRec; clinical application of this finding should be confirmed in other studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02269267.

Financial distress among breast cancer survivors.

AIMS: there has been an increasing awareness of the potential for oncology care to result in long-term financial burdens and financial toxicity. Patients who report cancer-related financial problems or high costs are more likely to forgo or delay prescription medications and medical care. MATERIALS AND METHODS: we examined financial distress using data from a survey of 164 breast cancer survivors who had completed primary therapy for the disease. KEY FINDINGS: among respondents, 8.6% (13 of 151) reported that "being less able to provide for the financial needs of their family" was as a severe problem; 14.4% (22 of 153) reported "difficulty in meeting medical expenses" was a severe problem; and 8.4% (13 of 154) reported that "no money for cost of or co-payment for medical visits" was a severe problem. About 8.4% (13 of 154) of the respondents reported that "no money for cost of or co-payment for medicine" was a severe problem. In logistic regression analysis, younger age and lower household income were significant predictors of financial distress. In multiple linear regression analysis, younger age and lower household income were significant predictors of financial distress. SIGNIFICANCE: financial toxicity remains a major issue in breast cancer care. Efforts are needed to ensure patients experiencing high levels of financial toxicity are able to access recommended care. In addition, patients should talk with their providers about the costs of oncology care and about opportunities to reduce costs while maintaining high quality of care.

Ultra-accurate Duplex Sequencing for the assessment of pretreatment ABL1 kinase domain mutations in Ph+ ALL.

Mutations of ABL1 are the dominant mechanism of relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). We performed highly accurate Duplex Sequencing of exons 4-10 of ABL1 on bone marrow or peripheral blood samples from 63 adult patients with previously untreated Ph + ALL who received induction with intensive chemotherapy plus a BCR-ABL1 TKI. We identified ABL1 mutations prior to BCR-ABL1 TKI exposure in 78% of patients. However, these mutations were generally present at extremely low levels (median variant allelic frequency 0.008% [range, 0.004%-3.71%] and did not clonally expand and lead to relapse in any patient, even when the pretreatment mutation was known to confer resistance to the TKI received. In relapse samples harboring a TKI-resistant ABL1 mutation, the corresponding mutation could not be detected pretreatment, despite validated sequencing sensitivity of Duplex Sequencing down to 0.005%. In samples under the selective pressure of ongoing TKI therapy, we detected low-level, emerging resistance mutations up to 5 months prior to relapse. These findings suggest that pretreatment ABL1 mutation assessment should not guide upfront TKI selection in Ph + ALL, although serial testing while on TKI therapy may allow for early detection of clinically actionable resistant clones.

Treatment value of second-generation BCR-ABL1 tyrosine kinase inhibitors compared with imatinib to achieve treatment-free remission in patients with chronic myeloid leukaemia: a modelling study.

BACKGROUND: Treatment-free remission in chronic myeloid leukaemia-ie, achievement of a sustained deep molecular response leading to discontinuation of BCR-ABL1 tyrosine kinase inhibitor (TKI) therapy-has become a potential aim of therapy. Highly priced second-generation TKIs might offer deep molecular response status more quickly and for more patients than imatinib; however, with the availability and lower cost of generic imatinib, the value of second-generation TKIs as frontline therapy for this particular treatment endpoint remains unknown. We aimed to assess the potential value of second-generation TKIs used as frontline therapy in patients with chronic myeloid leukaemia in chronic phase in relation to the probability of achieving sustained deep molecular responses compared with generic imatinib, and the associated cost of each modality. METHODS: We used a decision analytic model to consider the value of different TKI approaches from the payer's perspective. The proportion of patients achieving sustained deep molecular response after 5 years of treatment in chronic phase was estimated at 26% with imatinib and 44% with second-generation TKIs. We also modelled more favourable scenarios of the proportion of patients achieving such response with second-generation TKIs at 66%, 88%, and a near-perfect response of 99%. For each scenario, we examined the impact of the combination of health utilities for chronic-phase chronic myeloid leukaemia (base case 0·89, range 0-1) and the annual cost of second-generation TKIs (base case US$152 814 [ie, the price of nilotinib in the USA], range 0-240 000) on the cost-effectiveness of second-generation TKIs compared with generic imatinib. We used different price scenarios for generic imatinib in the USA (average price $35 000 per year; lowest price $4400 per year), Europe ($4000 per year), and developing countries ($2100 per year). We calculated incremental cost-effectiveness ratios (ICERs) and assessed cost-effectiveness by considering two societal willingness-to-pay thresholds: $50 000 per quality-adjusted life-year (QALY) in all markets and $200 000 per QALY in the USA. FINDINGS: In the base case, we obtained an ICER of $22 765 208, meaning that second-generation TKIs as frontline therapy to achieve sustained deep molecular response was not cost-effective under either of the societal willingness-to-pay thresholds. In our sensitivity analyses, none of the explored scenarios showed potential treatment value for use of second-generation TKIs at the current prices in the USA or at the price of $30 000-40 000 per year elsewhere. For example, considering a scenario in the USA using second-generation TKIs versus imatinib (annual price $4400 per year) with the potential benefit in favour of second-generation TKI (willingness to pay $200 000 per QALY, 66% of patients achieving sustained deep molecular response, and health utility of the chronic phase of 0·1), the cost of second-generation TKIs would need to be less than $25 000 per year to be a cost-effective option. Under the same conditions in developing nations, with a price of generic imatinib of $2100 per year and a willingness to pay of $50 000 per QALY, the annual price of second-generation TKIs should not exceed $10 000 per year of therapy. INTERPRETATION: Considering the current prices of second-generation TKIs and of generic imatinib under different pricing scenarios in the USA, Europe, and developing countries, second-generation TKIs at current prices do not offer good value as frontline therapy in chronic myeloid leukaemia in order to achieve sustained deep molecular response and treatment-free remission. FUNDING: National Cancer Institute.

Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia.

Outcomes for patients with chronic myeloid leukemia (CML) have substantially improved due to advances in drug development and rational treatment intervention strategies. Despite these significant advances there are still unanswered questions on patient management regarding how to more reliably predict treatment failure at the time of diagnosis and how to select frontline tyrosine kinase inhibitor (TKI) therapy for optimal outcome. The BCR-ABL1 transcript level at diagnosis has no established prognostic impact and cannot guide frontline TKI selection. BCR-ABL1 mutations are detected in ~50% of TKI resistant patients but are rarely responsible for primary resistance. Other resistance mechanisms are largely uncharacterized and there are no other routine molecular testing strategies to facilitate the evaluation and further stratification of TKI resistance. Advances in next-generation sequencing technology has aided the management of a growing number of other malignancies, enabling the incorporation of somatic mutation profiles in diagnosis, classification, and prognostication. A largely unexplored area in CML research is whether expanded genomic analysis at diagnosis, resistance, and disease transformation can enhance patient management decisions, as has occurred for other cancers. The aim of this article is to review publications that reported mutated cancer-associated genes in CML patients at various disease phases. We discuss the frequency and type of such variants at initial diagnosis and at the time of treatment failure and transformation. Current limitations in the evaluation of mutants and recommendations for future reporting are outlined. The collective evaluation of mutational studies over more than a decade suggests a limited set of cancer-associated genes are indeed recurrently mutated in CML and some at a relatively high frequency. Genomic studies have the potential to lay the foundation for improved diagnostic risk classification according to clinical and genomic risk, and to enable more precise early identification of TKI resistance.

Health reform in Mexico: governance and potential outcomes.

Adopting key mechanisms to restructure public policy in developing countries is a crucial political task. The strengthening of infrastructure of health services, care quality, monitoring and population health; all might contribute to assuring the functionality of a national system for health monitoring and care. Over the last decades, the Mexican government has launched wide-ranging political reforms aiming to overcome socioeconomic and environmental problems, namely health, education, finances, energy and pension. The proposed (but yet not implemented) health reform in Mexico during E. Peña Nieto's administration (2012-2018) pretended an adjustment in Article 4 of the Mexican Constitution to compact medical care and reduce the State's responsibility to a provision of minimum health packages for the population. Here we use a simple analytical model to describe and interprete the concepts of context, process, actors and content and the outcome of three of the most important resulting components of this intended reform i.e. universality, basic packages, and 'outsourcing'. In light of the start of the Mexico's new federal administration, we argue that, if not properly defined by all actors, the implementation of such structural health reform in Mexico would precipitate a model of private/public association exacerbating a crisis of political representation, human rights, justice and governance.

Bone marrow core biopsy in 508 consecutive patients with chronic myeloid leukemia: Assessment of potential value.

BACKGROUND: The diagnosis of chronic myeloid leukemia (CML) is based on characteristic clinical and laboratory findings and the presence of BCR/ABL1 in the blood and/or bone marrow (BM). The utility of BM core biopsy in the workup of patients with CML has been questioned. METHODS: The potential added value of BM biopsy versus aspiration in the workup of a single-institution series of 508 patients with CML at their initial presentation was systematically assessed. BM biopsy was considered essential when it was needed to establish the disease phase, often because blast counts derived from aspirate smears were misleading because the biopsy specimen was more representative of the disease. BM biopsy was considered helpful if it was needed for other nonessential reasons. RESULTS: In 127 patients (25%), BM biopsy was either essential (109 patients) or helpful (18 patients). Patients with accelerated-phase (AP) or blast-phase (BP) disease often required a biopsy related to essential reasons. High-grade myelofibrosis (MF) was more frequent in patients with AP/BP disease than patients with chronic-phase disease (P = .0005), and the identification of BP disease required a BM biopsy assessment in 75% of the patients (P = .001). A follow-up BM evaluation more often yielded inadequate aspirates in patients with inadequate BM aspirates at the time of their initial diagnosis. CONCLUSIONS: BM core biopsy remains valuable in the workup of 25% of patients with CML because it facilitates identification of the disease phase or MF. The initial grade of MF is associated with the disease stage and outcome after therapy. BM biopsy is, therefore, indicated for patients with CML who have AP/BP disease or other findings suggestive of progressive disease.

[Cross-cultural adaptation of the community-acquired pneumonia score questionnaire in patients with mild-to-moderate pneumonia in Colombia].

INTRODUCTION: One of the strategies for the rational use of antibiotics is the use of the score for community-acquired pneumonia (CAP Score). This instrument clinically evaluates patients with community-acquired pneumonia, thereby facilitating decision making regarding the early and safe withdrawal of antibiotics. OBJECTIVE: To generate a translation and cross-cultural adaptation of the Community-Acquired Pneumonia (CAP) Score questionnaire in Spanish. MATERIALS AND METHODS: Authorization for cross-cultural adaptation of the Community-Acquired Pneumonia (CAP) Score questionnaire was obtained; the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the European Organisation for Research and Treatment of Cancer (EORTC) were carried out through the following stages: forward translation, reconciliation, backward translation, harmonization, obtaining a provisional questionnaire, and applying the questionnaire in a pilot test. The pilot test was conducted at a second-level public hospital in Bogotá after the study was approved by the ethics and research institutional boards. RESULTS: The changes suggested by the forward translators were applied. There were no discrepancies between the backward and forward translations, consequently, no revisions were necessary. Five items had modifications based on suggestions made by eleven patients hospitalized with a diagnosis of community-acquired pneumonia during the pilot test. CONCLUSIONS: A Spanish version of the Community-Acquired Pneumonia (CAP) Score was crossculturally adapted and is now available.