Drug Repurposing for Cancers With Limited Survival: Protocol for a Retrospective Cohort Study

Only 5% of the molecules tested in oncology phase 1 trials reach the market after an average of 7.5 years of waiting and at a cost of tens of millions of dollars. To reduce the cost and shorten the time of discovery of new treatments, drug repurposing (research with molecules already approved for another indication) and the use of secondary data (not collected for the purpose of research) have been proposed. Due to advances in informatics in clinical care, secondary data can, in some cases, be of equal quality to primary data generated through prospective studies.Objective: The objective of this study is to identify drugs currently marketed for other indications that may have an effect on the prognosis of patients with cancer.Methods: We plan to monitor a cohort of patients with high-lethality cancers treated in the public health system of Catalonia between 2006 and 2012, retrospectively, for survival for 5 years after diagnosis or until death. A control cohort, comprising people without cancer, will also be retrospectively monitored for 5 years. The following study variables will be extracted from different population databases: type of cancer (patients with cancer cohort), date and cause of death, pharmacological treatment, sex, age, and place of residence. During the first stage of statistical analysis of the patients with cancer cohort, the drugs consumed by the long-term survivors (alive at 5 years) will be compared with those consumed by nonsurvivors. In the second stage, the survival associated with the consumption of each relevant drug will be analyzed. For the analyses, groups will be matched for potentially confounding variables, and multivariate analyses will be performed to adjust for residual confounding variables if necessary. The control cohort will be used to verify whether the associations found are exclusive to patients with cancer or whether they also occur in patients without cancer.Results: We anticipate discovering multiple significant associations between commonly used drugs and the survival outcomes of patients with cancer. We expect to publish the initial results in the first half of 2024.Conclusions: This retrospective study may identify several commonly used drugs as candidates for repurposing in the treatment of various cancers. All analyses are considered exploratory; therefore, the results will have to be confirmed in subsequent clinical trials. However, the results of this study may accelerate drug discovery in oncology

Incidence of urinary incontinence after hip fracture surgery and associated risk factors: a prospective study

Background The contribution of the postoperative process to developing or worsening urinary incontinence (UI) after hip fracture surgery (HFS) remains unclear. We aimed to evaluate UI incidence and worsening among older patients undergoing HFS, and explore associated risk factors.Methods This prospective cohort study included patients >= 75 years admitted between October 2019 and October 2021 to the Traumatology Service of three hospitals in the Consorci Sanitari de Alt-Pened & egrave;s i Garraf (Barcelona, Spain) with hip fracture requiring surgical treatment. UI was assessed using the first two questions of the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) at baseline and at days 30 (+/- 3 days) and 90 (+/- 3 days) after HFS. Surgery-related data and post-surgical complications were recorded.Results A total of 248 patients with a mean (SD) age of 85.8 (6.78) years were included; 77.8% were female and 154 (62.1%) had UI at baseline. After HFS, 3.24% experienced urinary tract infections (UTIs), 3.64%, acute urinary retention (AUR), 8.57%, constipation, and 53.9%, prolonged catheterization (> 24 h). Fifty-eight patients without baseline UI developed UI at 30 days, resulting in a UI incidence of 61.7% (95% CI 51.1-71.54) between days 0 and 30. Of the 248 patients, 146 (59.1%) experienced worsening of UI. AUR and UTIs were identified as risk factors for UI development and worsening after HFS, respectively.Conclusion The incidence of UI in older patients after HFS is significant. Patient management protocols should consider AUR and UTIs to reduce or eliminate the incidence of UI in older patients undergoing HFS

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Pseudorapidity and transverse-momentum distributions of charged particles in proton-proton collisions at root s=13 TeV

The pseudorapidity (eta) and transverse-momentum (p(T)) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy root s = 13 TeV. The pseudorapidity distribution in vertical bar eta vertical bar <1.8 is reported for inelastic events and for events with at least one charged particle in vertical bar eta vertical bar <1. The pseudorapidity density of charged particles produced in the pseudorapidity region vertical bar eta vertical bar <0.5 is 5.31 +/- 0.18 and 6.46 +/- 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 <p(T) <20 GeV/c and vertical bar eta vertical bar <0.8 for events with at least one charged particle in vertical bar eta vertical bar <1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Elliptic flow of muons from heavy-flavour hadron decays at forward rapidity in Pb-Pb collisions at root s(NN)=2.76TeV

The elliptic flow, v(2), of muons from heavy-flavour hadron decays at forward rapidity (2.5 <y <4) is measured in Pb-Pb collisions at root s(NN)= 2.76TeVwith the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee-Yang zeros methods are used. The dependence of the v(2) of muons from heavy-flavour hadron decays on the collision centrality, in the range 0-40%, and on transverse momentum, p(T), is studied in the interval 3 <p(T)<10 GeV/c. A positive v(2) is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10-20% and 20-40% centrality classes) for the p(T) interval from 3 to about 5GeV/c with a significance larger than 3 sigma, based on the combination of statistical and systematic uncertainties. The v(2) magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6 <p(T)<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe