Project description:BackgroundThe legal framework and funding mechanisms of the national health research system were recently reformed in Mexico. A study of the resource allocation for health research is still missing. We identified the health research areas funded by the National Council on Science and Technology (CONACYT) and examined whether research funding has been aligned to national health problems.Methods and findingsWe collected the information to create a database of research grant projects supported through the three main Sectoral Funds managed by CONACYT between 2003 and 2010. The health-related projects were identified and classified according to their methodological approach and research objective. A correlation analysis was carried out to evaluate the association between disease-specific funding and two indicators of disease burden. From 2003 to 2010, research grant funding increased by 32% at a compound annual growth rate of 3.5%. By research objective, the budget fluctuated annually resulting in modest increments or even decrements during the period under analysis. The basic science category received the largest share of funding (29%) while the less funded category was violence and accidents (1.4%). The number of deaths (? = 0.51; P<0.001) and disability-adjusted life years (DALYs; ? = 0.33; P = 0.004) were weakly correlated with the funding for health research. Considering the two indicators, poisonings and infectious and parasitic diseases were among the most overfunded conditions. In contrast, congenital anomalies, road traffic accidents, cerebrovascular disease, and chronic obstructive pulmonary disease were the most underfunded conditions.ConclusionsAlthough the health research funding has grown since the creation of CONACYT sectoral funds, the financial effort is still low in comparison to other Latin American countries with similar development. Furthermore, the great diversity of the funded topics compromises the efficacy of the investment. Better mechanisms of research priority-setting are required to adjust the research portfolio to the new health panorama of Mexican population.
Project description:BackgroundDespite demographic changes, there is still no systematic and comparable differentiation of nursing care reporting on a small-scale level in Germany, where outpatient long-term care is depicted. This article presents findings of care assessment data of the Medical Service of Bavaria and draws conclusions for future reporting on nursing.MethodsFor the analysis, anonymised initial long-term care assessments of the Bavarian Medical Service of 2019 were evaluated exemplarily using descriptive methods. The study describes the characteristics of persons with a care level recommendation, the distribution of care level categories, medical diagnoses and degree of independence in the areas of life.ResultsThe persons assessed were on average 80 years old. At the time of the initial assessment, the largest proportion of persons with an assigned care level lived in an outpatient setting. Care level (PG) 1 (slight impairment of independence or abilities) was assigned to 35.1% of the insured, PG 2 (considerable impairment) to 43.1%, PG 3 (severe impairment) to 16.6%, PG 4 and 5 (most severe impairment) were each rarely assigned at the time of the initial assessment (3.9% and 1.4%, respectively). Medical diagnoses were dominated by gait and mobility disorders, unspecified dementia, heart failure and senility. In particular, there were impairments in the areas of 'mobility' and 'organisation of everyday life and social contacts'.ConclusionsThe data available from the German Medical Service may be highly relevant to health research and policy and may provide a basis for planning interventions in long-term care.
Project description:PURPOSE:Multi-gene signatures provide biological insight and risk stratification in breast cancer. Intrinsic molecular subtypes defined by mRNA expression of 50 genes (PAM50) are prognostic in hormone-receptor positive postmenopausal breast cancer. Yet, for 25-40% in the PAM50 intermediate risk group, long-term risk remains uncertain. Our study aimed to (i) test the long-term prognostic value of the PAM50 signature in pre- and post-menopausal breast cancer; (ii) investigate if the PAM50 model could be improved by addition of other mRNAs implicated in oncogenesis. METHODS:We used archived FFPE samples from 1723 breast cancer survivors; high quality reads were obtained on 1253 samples. Transcript expression was quantified using a custom codeset with probes for >?100 targets. Cox models assessed gene signatures for breast cancer relapse and survival. RESULTS:Over 15?+ years of follow-up, PAM50 subtypes were (P?<?0.01) associated with breast cancer outcomes after accounting for tumor stage, grade and age at diagnosis. Results did not differ by menopausal status at diagnosis. Women with Luminal B (versus Luminal A) subtype had a >?60% higher hazard. Addition of a 13-gene hypoxia signature improved prognostication with >?40% higher hazard in the highest vs lowest hypoxia tertiles. CONCLUSIONS:PAM50 intrinsic subtypes were independently prognostic for long-term breast cancer survival, irrespective of menopausal status. Addition of hypoxia signatures improved risk prediction. If replicated, incorporating the 13-gene hypoxia signature into the existing PAM50 risk assessment tool, may refine risk stratification and further clarify treatment for breast cancer.
Project description:Evidence suggests that the perioperative period and the excision of the primary tumour can promote the development of metastases—the main cause of cancer-related mortality. This Review first presents the assertion that the perioperative timeframe is pivotal in determining long-term cancer outcomes, disproportionally to its short duration (days to weeks). We then analyse the various aspects of surgery, and their consequent paracrine and neuroendocrine responses, which could facilitate the metastatic process by directly affecting malignant tissues, and/or through indirect pathways, such as immunological perturbations. We address the influences of surgery-related anxiety and stress, nutritional status, anaesthetics and analgesics, hypothermia, blood transfusion, tissue damage, and levels of sex hormones, and point at some as probable deleterious factors. Through understanding these processes and reviewing empirical evidence, we provide suggestions for potential new perioperative approaches and interventions aimed at attenuating deleterious processes and ultimately improving treatment outcomes. Specifically, we highlight excess perioperative release of catecholamines and prostaglandins as key deleterious mediators of surgery, and we recommend blockade of these responses during the perioperative period, as well as other low-risk, low-cost interventions. The measures described in this Review could transform the perioperative timeframe from a prominent facilitator of metastatic progression, to a window of opportunity for arresting and/or eliminating residual disease, potentially improving long-term survival rates in patients with cancer.
Project description:The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases. A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre-R&D Blueprint approach to disease prioritization and increased confidence in the results.
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide with an estimated number of 2.7-6.1 million cases in the United States (US) alone. The incidence of AF is expected to increase 2.5 fold over the next 50 years in the US. The management of AF is complex and includes mainly three aspects; restoration of sinus rhythm, control of ventricular rate and prevention of systemic thromboembolism. AF as a cause of systemic embolization has been well known for many years, and majority of patients are on oral anticoagulants (OACs) to prevent this. Many times, a patient may not be in AF chronically, nor is the AF burden (the amount of time patient is in AF out of the total monitored time) calculated. We present three cases of new onset transient AF triggered by temporary stressors. We were able to restore normal sinus rhythm (NSR) with chemical cardioversion. As per 2014 American College of Cardiology (ACC)/American Heart Association (AHA) recommendations, we started all three patients on OACs based on CHA2DS2VASc score ≥2. However, the patients refused long term OACs after restoration of NSR and correction of the temporary enticing stressors. In any case, the decision to start OACs would have had its own risks. Here we describe how antiarrhythmic drugs were used to maintain NSR, all while they were continuously monitored to determine the need to continue OACs.
Project description:Genomics and molecular imaging, along with clinical and translational research have transformed biomedical science into a data-intensive scientific endeavor. For researchers to benefit from Big Data sets, developing long-term biomedical digital data preservation strategy is very important. In this opinion article, we discuss specific actions that researchers and institutions can take to make research data a continued resource even after research projects have reached the end of their lifecycle. The actions involve utilizing an Open Archival Information System model comprised of six functional entities: Ingest, Access, Data Management, Archival Storage, Administration and Preservation Planning. We believe that involvement of data stewards early in the digital data life-cycle management process can significantly contribute towards long term preservation of biomedical data. Developing data collection strategies consistent with institutional policies, and encouraging the use of common data elements in clinical research, patient registries and other human subject research can be advantageous for data sharing and integration purposes. Specifically, data stewards at the onset of research program should engage with established repositories and curators to develop data sustainability plans for research data. Placing equal importance on the requirements for initial activities (e.g., collection, processing, storage) with subsequent activities (data analysis, sharing) can improve data quality, provide traceability and support reproducibility. Preparing and tracking data provenance, using common data elements and biomedical ontologies are important for standardizing the data description, making the interpretation and reuse of data easier. The Big Data biomedical community requires scalable platform that can support the diversity and complexity of data ingest modes (e.g. machine, software or human entry modes). Secure virtual workspaces to integrate and manipulate data, with shared software programs (e.g., bioinformatics tools), can facilitate the FAIR (Findable, Accessible, Interoperable and Reusable) use of data for near- and long-term research needs.
Project description:ImportanceThe long-term outcomes among men with prostate cancer (PC) whose disease is managed with active surveillance (AS) remains unknown.ObjectiveTo develop a simulation model with a 30-year follow-up for men with PC managed with AS.Design, setting, and participantsIn this cohort study, a state transition model was created using data from Prostate Cancer data Base Sweden (PCBaSe) on 23 655 men diagnosed with PC and managed with deferred treatment to estimate treatment trajectories. A simulation was performed with 100 000 men in each combination of age at diagnosis, Charlson Comorbidity Index, and PC risk with a follow-up of 30 years.Main outcomes and measuresDeath from PC and death from other causes were estimated, and the proportion of time without active PC treatment was assessed until date of death or age 85 years.ResultsThis study included 23 655 men from PCBaSe with a median age at diagnosis of 69 years (IQR, 64-74 years). Of these, 16 177 men underwent active surveillance for PC and 7478 underwent watchful waiting. The proportion of men who were diagnosed at age 55 years and died of PC before age 85 years was 9% for very low-risk PC, 13% for low-risk PC, and 15% for intermediate-risk PC. Among men with a Charlson Comorbidity Index of 0 who were diagnosed at age 70 years, the corresponding percentages were 3%, 6%, and 7%, respectively. The mean proportion of remaining life-years without active PC treatment for men diagnosed at age 55 years was 12 of 25 years (48%) for very low-risk PC, 9 of 25 years (36%) for low-risk PC, and 7 of 25 (29%) for intermediate-risk PC. For men aged 70 years, the corresponding numbers were 10 of 13 years (77%), 9 of 13 years (66%), and 8 of 13 years (60%), respectively. Men with intermediate-risk PC who were younger than 60 years at diagnosis had a high risk of PC death (12%-15%) and fewer remaining life-years without active PC treatment (29%-33%). In contrast, men with low-risk PC who were older than 65 years at diagnosis had a lower risk of PC death (3%-5%) and more remaining life-years without active PC treatment (62%-77%).Conclusions and relevanceThe findings of this Swedish cohort study suggest that active surveillance may be a safe strategy for disease management among men with PC who were older than 65 years at diagnosis.
Project description:BackgroundOnly truly long-term follow-up can determine the ultimate outcome in prostate cancer. Most studies have a median follow-up of less than 10 years and then project outcomes out to 15 and 20 years. We sought to follow patients for at least 20 years. Materials and Methods. We followed 754 prostate cancer patients treated with radical prostatectomy from 1988 to 1995 for a median follow-up (in survivors) of 23.9 years. We excluded lymph node and seminal vesicle positive patients and an additional 47 patients that did not have baseline prostate-specific antigen (PSA). This left 581 patients for analysis.ResultsWith the factors of PSA, Gleason score, and extraprostatic extension/margin positivity, we could partition patients into three risk groups for biochemical failure (low, intermediate, and high). In further analysis, we found that the risk of metastatic disease in the first two groups was almost identical (4% and 5%, respectively), while it was 19% in the high-risk group. High-risk patients were those with PSA >20 ng/ml and/or Gleason >7, or Gleason 7 + PSA 10-20 + epe (and or margin) positive. They had a 22% prostate cancer mortality.ConclusionIn patients with truly long-term follow-up after prostatectomy for prostate cancer, the risk of metastatic disease and cancer death is very low. Patients with the lower risk findings do not appear to benefit from routine follow-up after 10 years free of biochemical recurrence. With a higher risk of later failure, we recommend that the higher risk patients be followed at least intermittently for another 5 years (out to 15 years).
Project description:Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups.