Avoidable Adverse Events Related to Ignoring the Do-Not-Do Recommendations: A Retrospective Cohort Study Conducted in the Spanish Primary Care Setting

Objective This study aimed to measure the frequency and severity of avoidable adverse events (AAEs) related to ignoring do-not-do recommendations (DNDs) in primary care. Methods A retrospective cohort study analyzing the frequency and severity of AAEs related to ignoring DNDs (7 from family medicine and 3 from pediatrics) was conducted in Spain. Data were randomly extracted from computerized electronic medical records by a total of 20 general practitioners and 5 pediatricians acting as reviewers; data between February 2018 and September 2019 were analyzed. Results A total of 2557 records of adult and pediatric patients were reviewed. There were 1859 (72.7%) of 2557 (95% confidence interval [CI], 71.0%-74.4%) DNDs actions in 1307 patients (1507 were performed by general practitioners and 352 by pediatricians). Do-not-do recommendations were ignored more often in female patients (P < 0.0001). Sixty-nine AAEs were linked to ignoring DNDs (69/1307 [5.3%]; 95% CI, 4.1%-6.5%). Of those, 54 (5.1%) of 1062 were in adult patients (95% CI, 3.8%-6.4%) and 15 (6.1%) of 245 in pediatric patients (95% CI, 3.1%-9.1%). In adult patients, the majority of AAEs (51/901 [5.7%]; 95% CI, 4.2%-7.2%) occurred in patients 65 years or older. Most AAEs were characterized by temporary minor harm both in adult patients (28/54 [51.9%]; 95% CI, 38.5%-65.2%) and pediatric patients (15/15 [100%]). Conclusions These findings provide a new perspective about the consequences of low-value practices for the patients and the health care systems. Ignoring DNDs could place patients at risk, and their safety might be unnecessarily compromised

Inverse-probability weighting and multiple imputation for evaluating selection bias in the estimation of childhood obesity prevalence using data from electronic health records

Background and objectives: Height and weight data from electronic health records are increasingly being used to estimate the prevalence of childhood obesity. Here, we aim to assess the selection bias due to missing weight and height data from electronic health records in children older than five. Methods: Cohort study of 10,811 children born in Navarra (Spain) between 2002 and 2003, who were still living in this region by December 2016. We examined the differences between measured and non-measured children older than 5 years considering weight-associated variables (sex, rural or urban residence, family income and weight status at 2–5 yrs). These variables were used to calculate stabilized weights for inverse-probability weighting and to conduct multiple imputation for the missing data. We calculated complete data prevalence and adjusted prevalence considering the missing data using inverse-probability weighting and multiple imputation for ages 6 to 14 and group ages 6 to 9 and 10 to 14. Results: For 6–9 years, complete data, inverse-probability weighting and multiple imputation obesity age-adjusted prevalence were 13.18% (95% CI: 12.54–13.85), 13.22% (95% CI: 12.57–13.89) and 13.02% (95% CI: 12.38–13.66) and for 10–14 years 8.61% (95% CI: 8.06–9.18), 8.62% (95% CI: 8.06–9.20) and 8.24% (95% CI: 7.70–8.78), respectively. Conclusions: Ages at which well-child visits are scheduled and for the 6 to 9 and 10 to 14 age groups, weight status estimations are similar using complete data, multiple imputation and inverse-probability weighting. Readily available electronic health record data may be a tool to monitor the weight status in children

SOBRINA Spanish study-analysing the frequency, cost and adverse events associated with overuse in primary care: protocol for a retrospective cohort study

Introduction Several institutions and quality national agencies have fostered the creation of recommendations on what not to do to reduce overuse in clinical practice. In primary care, their impact has hardly been studied. The frequency of adverse events (AEs) associated with doing what must not be done has not been analysed, either. The aim of this study is to measure the frequency of overuse and AEs associated with doing what must not be done (commission errors) in primary care and their cost. Methods and analysis A coordinated, multicentric, national project. A retrospective cohort study using computerised databases of primary care medical records from national agencies and regional health services will be conducted to analyse the frequency of the overuse due to ignore the do-not-do recommendations, and immediately afterwards, depending on their frequency, a representative random sample of medical records will be reviewed with algorithms (triggers) that determine the frequency of AEs associated with these recommendations. Cost will determine by summation of the direct costs due to the consultation, pharmacy, laboratory and imaging activities according to the cases. Ethics and dissemination The study protocol has been approved by the Ethics Committee of Primary Care Research of the Valencian Community. We aim to disseminate the findings through international peerreviewed journals and on the website (http://www. nohacer. es/). Outcomes will be used to incorporate algorithms into the electronic history to assist in making clinical decisions

Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment

Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the surface of NCAM (neuronal cell adhesion molecule) in a number of cancers where it modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis and is strongly associated with poor clinical prognosis. We have carried out the first investigation into the effect of polySia expression on the behaviour of cancer cells in hypoxia, a key source of chemoresistance in tumours. The role of polysialylation and associated tumour cell migration and cell adhesion were studied in hypoxia, along with effects on cell survival and the potential role of HIF-1. Our findings provide the first evidence that polySia expression sustains migratory capacity and is associated with tumour cell survival in hypoxia. Initial mechanistic studies indicate a potential role for HIF-1 in sustaining polySia-mediated migratory capacity, but not cell survival. These data add to the growing body of evidence pointing to a crucial role for the polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide the first evidence to suggest that polySia is associated with an aggressive phenotype in tumour hypoxia. These results have significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and for targeting hypoxic cancer cells

Improved Phylogenetic Analyses Corroborate a Plausible Position of Martialis heureka in the Ant Tree of Life

Martialinae are pale, eyeless and probably hypogaeic predatory ants. Morphological character sets suggest a close relationship to the ant subfamily Leptanillinae. Recent analyses based on molecular sequence data suggest that Martialinae are the sister group to all extant ants. However, by comparing molecular studies and different reconstruction methods, the position of Martialinae remains ambiguous. While this sister group relationship was well supported by Bayesian partitioned analyses, Maximum Likelihood approaches could not unequivocally resolve the position of Martialinae. By re-analysing a previous published molecular data set, we show that the Maximum Likelihood approach is highly appropriate to resolve deep ant relationships, especially between Leptanillinae, Martialinae and the remaining ant subfamilies. Based on improved alignments, alignment masking, and tree reconstructions with a sufficient number of bootstrap replicates, our results strongly reject a placement of Martialinae at the first split within the ant tree of life. Instead, we suggest that Leptanillinae are a sister group to all other extant ant subfamilies, whereas Martialinae branch off as a second lineage. This assumption is backed by approximately unbiased (AU) tests, additional Bayesian analyses and split networks. Our results demonstrate clear effects of improved alignment approaches, alignment masking and data partitioning. We hope that our study illustrates the importance of thorough, comprehensible phylogenetic analyses using the example of ant relationships

Spin chemistry investigation of peculiarities of photoinduced electron transfer in donor-acceptor linked system

Photoinduced intramolecular electron transfer in linked systems, (R,S)- and (S,S)-naproxen-N-methylpyrrolidine dyads, has been studied by means of spin chemistry methods [magnetic field effect and chemically induced dynamic nuclear polarization (CIDNP)]. The relative yield of the triplet state of the dyads in different magnetic field has been measured, and dependences of the high-field CIDNP of the N-methylpyrrolidine fragment on solvent polarity have been investigated. However, both (S,S)- and (R,S)-enantiomers demonstrate almost identical CIDNP effects for the entire range of polarity. It has been demonstrated that the main peculiarities of photoprocesses in this linked system are connected with the participation of singlet exciplex alongside with photoinduced intramolecular electron transfer in chromophore excited state quenching.This work was supported by the grants 08-03-00372 and 11-03-01104 of the Russian Foundation for Basic Research, and the grant of Priority Programs of the Russian Academy of Sciences, nr. 5.1.5.Magin, I.; Polyakov, N.; Khramtsova, E.; Kruppa, A.; Stepanov, A.; Purtov, P.; Leshina, T.... (2011). Spin chemistry investigation of peculiarities of photoinduced electron transfer in donor-acceptor linked system. Applied Magnetic Resonance. 41(2-4):205-220. https://doi.org/10.1007/s00723-011-0288-3S205220412-4J.S. Park, E. Karnas, K. Ohkubo, P. Chen, K.M. Kadish, S. Fukuzumi, C.W. Bielawski, T.W. Hudnall, V.M. Lynch, J.L. Sessler, Science 329, 1324–1327 (2010)S.Y. Reece, D.G. Nocera, Annu. Rev. Biochem. 78, 673–699 (2009)M.S. Afanasyeva, M.B. Taraban, P.A. Purtov, T.V. Leshina, C.B. Grissom, J. Am. Chem. Soc. 128, 8651–8658 (2006)M.A. Fox, M. Chanon, in Photoinduced Electron Transfer. C: Photoinduced Electron Transfer Reactions: Organic Substrates (Elsevier, New York, 1988), p. 754P.J. Hayball, R.L. Nation, F. Bochner, Chirality 4, 484–487 (1992)N. Suesa, M.F. Fernandez, M. Gutierrez, M.J. Rufat, E. Rotllan, L. Calvo, D. Mauleon, G. Carganico, Chirality 5, 589–595 (1993)A.M. Evans, J. Clin. Pharmacol. 36, 7–15 (1996)Y. Inoue, T. Wada, S. Asaoka, H. Sato, J.-P. Pete, Chem Commun. 4, 251–259 (2000)T. Yorozu, K. Hayashi, M. Irie, J. Am. Chem. Soc. 103, 5480–5548 (1981)N.J. Turro, in Modern Molecular Photochemistry (Benjamin/Cummings, San Francisco, 1978)K.M. Salikhov, Y.N. Molin, R.Z. Sagdeev, A.L. Buchachenko, in Spin Polarization and Magnetic Field Effects in Radical Reactions (Akademiai Kiado, Budapest, 1984), p. 419E.A. Weiss, M.A. Ratner, M.R. Wasielewski, J. Phys. Chem. A 107, 3639–3647 (2003)A.S. Lukas, P.J. Bushard, E.A. Weiss, M.R. Wasielewski, J. Am. Chem. Soc. 125, 3921–3930 (2003)R. Nakagaki, K. Mutai, M. Hiramatsu, H. Tukada, S. Nakakura, Can. J. Chem. 66, 1989–1996 (1988)M.C. Jim′enez, U. Pischel, M.A. Miranda, J. Photochem. Photobiol. C Photochem. Rev. 8, 128–142 (2007)S. Abad, U. Pischel, M.A. Miranda, Photochem. Photobiol. Sci. 4, 69–74 (2005)U. Pischel, S. Abad, L.R. Domingo, F. Bosca, M.A. Miranda, Angew. Chem. Int. Ed. 42, 2531–2534 (2003)G.L. Closs, R.J. Miller, J. Am. Chem. Soc. 101, 1639–1641 (1979)G.L. Closs, R.J. Miller, J. Am. Chem. Soc. 103, 3586–3588 (1981)M. Goez, Chem. Phys. Lett. 188, 451–456 (1992)I.F. Molokov, Y.P. Tsentalovich, A.V. Yurkovskaya, R.Z. Sagdeev, J. Photochem. Photobiol. A 110, 159–165 (1997)U. Pischel, S. Abad, M.A. Miranda, Chem. Commun. 9, 1088–1089 (2003)H. Hayashi, S. Nagakura, Bull. Chem. Soc. Jpn. 57, 322–328 (1984)Y. Sakaguchi, H. Hayashi, S. Nagakura, Bull. Chem. Soc. Jpn. 53, 39–42 (1980)H. Yonemura, H. Nakamura, T. Matsuo, Chem. Phys. Lett. 155, 157–161 (1989)N. Hata, M. Hokawa, Chem. Lett. 10, 507–510 (1981)M. Shiotani, L. Sjoeqvist, A. Lund, S. Lunell, L. Eriksson, M.B. Huang, J. Phys. Chem. 94, 8081–8090 (1990)E. Schaffner, H. Fischer, J. Phys. Chem. 100, 1657–1665 (1996)Y. Mori, Y. Sakaguchi, H. Hayashi, Chem. Phys. Lett. 286, 446–451 (1998)I.M. Magin, A.I. Kruppa, P.A. Purtov, Chem. Phys. 365, 80–84 (2009)K.K. Barnes, Electrochemical Reactions in Nonaqueous Systems (M. Dekker, New York, 1970), p. 560J. Bargon, J. Am. Chem. Soc. 99, 8350–8351 (1977)M. Goez, I. Frisch, J. Phys. Chem. A 106, 8079–8084 (2002)A.K. Chibisov, Russ. Chem. Rev. 50, 615–629 (1981)J. Goodman, K. Peters, J. Am. Chem. Soc. 107, 1441–1442 (1985)H. Cao, Y. Fujiwara, T. Haino, Y. Fukazawa, C.-H. Tung, Y. Tanimoto, Bull. Chem. Soc. Jpn. 69, 2801–2813 (1996)P.A. Purtov, A.B. Doktorov, Chem. Phys. 178, 47–65 (1993)A.I. Kruppa, O.I. Mikhailovskaya, T.V. Leshina, Chem. Phys. Lett. 147, 65–71 (1988)M.E. Michel-Beyerle, R. Haberkorn, W. Bube, E. Steffens, H. Schröder, H.J. Neusser, E.W. Schlag, H. Seidlitz, Chem. Phys. 17, 139–145 (1976)K. Schulten, H. Staerk, A. Weller, H.-J. Werner, B. Nickel, Z. Phys. Chem. 101, 371–390 (1976)K. Gnadig, K.B. Eisenthal, Chem. Phys. Lett. 46, 339–342 (1977)T. Nishimura, N. Nakashima, N. Mataga, Chem. Phys. Lett. 46, 334–338 (1977)M.G. Kuzmin, I.V. Soboleva, E.V. Dolotova, D.N. Dogadkin, High Eng. Chem. 39, 86–96 (2005

EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>The epithelial to mesenchymal transition (EMT) is a molecular process through which an epithelial cell undergoes transdifferentiation into a mesenchymal phenotype. The role of EMT in embryogenesis is well-characterized and increasing evidence suggests that elements of the transition may be important in other processes, including metastasis and drug resistance in various different cancers.</p> <p>Methods</p> <p>Agilent 4 × 44 K whole human genome arrays and selected reaction monitoring mass spectrometry were used to investigate mRNA and protein expression in A2780 cisplatin sensitive and resistant cell lines. Invasion and migration were assessed using Boyden chamber assays. Gene knockdown of <it>snail </it>and <it>slug </it>was done using targeted siRNA. Clinical relevance of the EMT pathway was assessed in a cohort of primary ovarian tumours using data from Affymetrix GeneChip Human Genome U133 plus 2.0 arrays.</p> <p>Results</p> <p>Morphological and phenotypic hallmarks of EMT were identified in the chemoresistant cells. Subsequent gene expression profiling revealed upregulation of EMT-related transcription factors including <it>snail, slug, twist2 </it>and <it>zeb2</it>. Proteomic analysis demonstrated up regulation of Snail and Slug as well as the mesenchymal marker Vimentin, and down regulation of E-cadherin, an epithelial marker. By reducing expression of <it>snail </it>and <it>slug</it>, the mesenchymal phenotype was largely reversed and cells were resensitized to cisplatin. Finally, gene expression data from primary tumours mirrored the finding that an EMT-like pathway is activated in resistant tumours relative to sensitive tumours, suggesting that the involvement of this transition may not be limited to <it>in vitro </it>drug effects.</p> <p>Conclusions</p> <p>This work strongly suggests that genes associated with EMT may play a significant role in cisplatin resistance in ovarian cancer, therefore potentially leading to the development of predictive biomarkers of drug response or novel therapeutic strategies for overcoming drug resistance.</p