European value-based healthcare benchmarking: moving from theory to practice.

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.

The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis.

The accurate repair of DNA double-strand breaks (DSBs), highly toxic DNA lesions, is crucial for genome integrity and is tightly regulated during the cell cycle. In mitosis, cells inactivate DSB repair in favor of a tethering mechanism that stabilizes broken chromosomes until they are repaired in the subsequent cell cycle phases. How this is achieved mechanistically is not yet understood, but the adaptor protein TOPBP1 is critically implicated in this process. Here, we identify CIP2A as a TOPBP1-interacting protein that regulates TOPBP1 localization specifically in mitosis. Cells lacking CIP2A display increased radio-sensitivity, micronuclei formation and chromosomal instability. CIP2A is actively exported from the cell nucleus in interphase but, upon nuclear envelope breakdown at the onset of mitosis, gains access to chromatin where it forms a complex with MDC1 and TOPBP1 to promote TOPBP1 recruitment to sites of mitotic DSBs. Collectively, our data uncover CIP2A-TOPBP1 as a mitosis-specific genome maintenance complex.

Cancer LncRNA Census 2 (CLC2): an enhanced resource reveals clinical features of cancer lncRNAs.

Long non-coding RNAs (lncRNAs) play key roles in cancer and are at the vanguard of precision therapeutic development. These efforts depend on large and high-confidence collections of cancer lncRNAs. Here, we present the Cancer LncRNA Census 2 (CLC2). With 492 cancer lncRNAs, CLC2 is 4-fold greater in size than its predecessor, without compromising on strict criteria of confident functional/genetic roles and inclusion in the GENCODE annotation scheme. This increase was enabled by leveraging high-throughput transposon insertional mutagenesis screening data, yielding 92 novel cancer lncRNAs. CLC2 makes a valuable addition to existing collections: it is amongst the largest, contains numerous unique genes (not found in other databases) and carries functional labels (oncogene/tumour suppressor). Analysis of this dataset reveals that cancer lncRNAs are impacted by germline variants, somatic mutations and changes in expression consistent with inferred disease functions. Furthermore, we show how clinical/genomic features can be used to vet prospective gene sets from high-throughput sources. The combination of size and quality makes CLC2 a foundation for precision medicine, demonstrating cancer lncRNAs' evolutionary and clinical significance.

MicroRNA-7a2 Regulates Prolactin in Developing Lactotrophs and Prolactinoma Cells.

Prolactin production is controlled by a complex and temporally dynamic network of factors. Despite this tightly coordinated system, pathological hyperprolactinemia is a common endocrine disorder that is often not understood, thereby highlighting the need to expand our molecular understanding of lactotroph cell regulation. MicroRNA-7 (miR-7) is the most highly expressed miRNA family in the pituitary gland and the loss of the miR-7 family member, miR-7a2, is sufficient to reduce prolactin gene expression in mice. Here, we used conditional loss-of-function and gain-of-function mouse models to characterize the function of miR-7a2 in lactotroph cells. We found that pituitary miR-7a2 expression undergoes developmental and sex hormone-dependent regulation. Unexpectedly, the loss of mir-7a2 induces a premature increase in prolactin expression and lactotroph abundance during embryonic development, followed by a gradual loss of prolactin into adulthood. On the other hand, lactotroph development is delayed in mice overexpressing miR-7a2. This regulation of lactotroph function by miR-7a2 involves complementary mechanisms in multiple cell populations. In mouse pituitary and rat prolactinoma cells, miR-7a2 represses its target Raf1, which promotes prolactin gene expression. These findings shed light on the complex regulation of prolactin production and may have implications for the physiological and pathological mechanisms underlying hyperprolactinemia.

[Benign prostate hyperplasia. Need to evaluate quality of life in the therapeutic process]. / Hiperplasia benigna de próstata. Necesidad de valorar la calidad de vida en el proceso terapéutico.

OBJECTIVE: To relate the symptoms of benign prostate hyperplasia (BPH) to their repercussions on quality of life. DESIGN: Multi-centred, observational, prospective study. SETTING: Primary care. PARTICIPANTS: Men with BPH in 2000-2003. Inclusion criteria were: agreeing to take part, being aged 50-79, and having moderate symptoms evaluated by means of the IPSS questionnaire. EXCLUSION CRITERIA: Previous treatment for BPH and having a chronic or disabling illness that might affect perception of quality of life. The presence of irritative and obstructive symptoms was appraised. MAIN MEASUREMENTS: The IPSS questionnaire appraising predominant symptoms and, through the last question, quality of life was self-administered. Descriptive statistics were worked out and differences in proportions of the different groups were analysed by the chi2 test, with differences taken as significant at P < .05. RESULTS: We got 536 replies, with average age 66.2. Nycturia was the most common symptom, suffered by 88.1% of patients. A total of 256 patients (47.8%) had irritation as main clinical symptom, and 280 (52.2%), obstruction. On analysing repercussions on quality of life, it was found that obstructive symptoms were worse tolerated: 65.7% versus 9.4% of the group with irritation. CONCLUSIONS: In treating BPH, we must bear in mind preferences of patients. They tolerate obstructive symptoms worse, and these are a criterion for referral to specialists and even surgery.

Hiperplasia benigna de próstata. Necesidad de valorar la calidad de vida en el proceso terapéutico / Benign prostate hyperplasia. Need to evaluate quality of life in the therapeutic process

Objetivo. Relacionar la sintomatología de la hiperplasia benigna de próstata (HBP) con la repercusión sobre la calidad de vida. Diseño. Multicéntrico, observacional y prospectivo. Emplazamiento. Atención primaria. Participantes. Varones de 50 a 79 años con HBP durante el período 2000-2003 con sintomatología moderada (cuestionario IPSS). Criterios de exclusión. Tratamiento previo para la HBP y presentar alguna enfermedad crónica o invalidante que pudiera alterar la percepción de la calidad de vida. Mediciones principales. Se autoadministró el cuestionario IPSS y se valoró la sintomatología predominante y mediante la última pregunta la calidad de vida. Se realizó un estadística descriptiva y se analizó mediante la prueba de la χ2. Resultados. Se realizaron 536 registros; la edad media fue de 66,2 años. Entre los síntomas destaca la nicturia como el más frecuente, con 88,1% de los registros. Se hallaron 256 pacientes (47,8%) con predominio de clínica irritativa y en 280 pacientes (52,2%), obstructiva. Al analizar la repercusión sobre la calidad de vida se obtuvo que los síntomas obstructivos son los peor tolerados (el 65,7 frente al 9,4% del grupo de clínica irritativa). Conclusiones. En el tratamiento de la HBP debemos tener en cuenta las preferencias del paciente, que tolera peor la sintomatología obstructiva que coincide con la que presenta criterio de derivación hacia una consulta especializada e incluso criterio quirúrgico

Objective. To relate the symptoms of benign prostate hyperplasia (BPH) to their repercussions on quality of life. Design. Multi-centred, observational, prospective study. Setting. Primary care. Participants. Men with BPH in 2000-2003. Inclusion criteria were: agreeing to take part, being aged 50-79, and having moderate symptoms evaluated by means of the IPSS questionnaire. Exclusion criteria. Previous treatment for BPH and having a chronic or disabling illness that might affect perception of quality of life. The presence of irritative and obstructive symptoms was appraised. Main measurements. The IPSS questionnaire appraising predominant symptoms and, through the last question, quality of life was self-administered. Descriptive statistics were worked out and differences in proportions of the different groups were analysed by the χ2 test, with differences taken as significant at P<.05. Results. We got 536 replies, with average age 66.2. Nycturia was the most common symptom, suffered by 88.1% of patients. A total of 256 patients (47.8%) had irritation as main clinical symptom, and 280 (52.2%), obstruction. On analysing repercussions on quality of life, it was found that obstructive symptoms were worse tolerated: 65.7% versus 9.4% of the group with irritation. Conclusions. In treating BPH, we must bear in mind preferences of patients. They tolerate obstructive symptoms worse, and these are a criterion for referral to specialists and even surgery