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1.
BMJ Open ; 14(4): e078647, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38604627

ABSTRACT

OBJECTIVES: To map the current use of paper-based and/or screen-based media for health education aimed at older people. DESIGN: A scoping review was reported following the Preferred Reporting Items of Systematic Reviews and Meta-analyses for Scoping Reviews checklist. DATA SOURCES: The search was carried out in seven databases (Scopus, Web of Science, Embase, Medline, CINAHL, ACM Guide to Computing Literature, PsycINFO), with studies available from 2012 to the date of the search in 2022, in English, Portuguese, Italian or Spanish. In addition, Google Scholar was searched to check the grey literature. The terms used in the search strategy were older adults, health education, paper and screen-based media, preferences, intervention and other related terms. ELIGIBILITY CRITERIA: Studies included were those that carried out health education interventions for older individuals using paper and/or screen-based media and that described barriers and/or facilitators to using these media. DATA EXTRACTION AND SYNTHESIS: The selection of studies was carried out by two reviewers. A data extraction form was developed with the aim of extracting and recording the main information from the studies. Data were analysed descriptively using Bardin's content analysis. RESULTS: The review included 21 studies that carried out health education interventions with different purposes, the main ones being promotion of physical activity, hypertension prevention and psychological health. All 21 interventions involved screen-based media on computers, tablets, smartphones and laptops, while only 4 involved paper-based media such as booklets, brochures, diaries, flyers and drawings. This appears to reflect a transition from paper to screen-based media for health education for the older population, in research if not in practice. However, analysis of facilitators and barriers to using both media revealed 10 design factors that could improve or reduce their use, and complementarity in their application to each media type. For example, screen-based media could have multimedia content, additional functionality and interactivity through good interaction design, but have low accessibility and require additional learning due to complex interface design. Conversely, paper-based media had static content and low functionality but high accessibility and availability and a low learning cost. CONCLUSIONS: We recommend having improved screen-based media design, continued use of paper-based media and the possible combination of both media through the new augmented paper technology. REGISTRATION NUMBER: Open Science Framework (DOI: 10.17605/OSF.IO/GKEAH).


Subject(s)
Checklist , Health Education , Aged , Humans , Ethnicity , Systematic Reviews as Topic
2.
Aust J Rural Health ; 32(1): 17-28, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37916478

ABSTRACT

OBJECTIVE: To assess timeliness, efficiency, health outcomes and cost-effectiveness of the 2018 redesigned Central Australian aeromedical retrieval model. DESIGN: Pre- and postimplementation observational study of all patients receiving telehealth consultations from remote medical practitioners (RMPs) or Medical Retrieval and Consultation Centre (MRaCC) physicians between 1/1/2015 and 29/2/2020. Descriptive and inferential statistics measuring system efficiency, timeliness, health outcomes and incremental cost-effectiveness. FINDINGS: There were 9%-10% reductions in rates of total aeromedical retrievals, emergency department admissions and hospitalisations postimplementation, all p-values < 0.001. Usage rates for total hospital bed days and ICU hours were 17% lower (both p < 0.001). After adjusting for periodicity (12% fewer retrievals on weekends), each postimplementation year, there were 0.7 fewer retrievals/day (p = 0.002). The mean time from initial consultation to aeromedical departure declined by 18 minutes post-implementation (115 vs. 97 min, p = 0.007). The hazard of death within 365 days was nonsignificant (0.912, 95% CI 0.743-1.120). Postimplementation, it cost $302 more per hospital admission and $3051 more per year of life saved, with a 75% probability of cost-effectiveness. These costs excluded estimated savings of $744,528/year in reduced hospitalisations and the substantial social and out-of-pocket costs to patients and their families associated with temporary relocation to Alice Springs. CONCLUSION: Central Australia's new critical care consultant-led aeromedical retrieval model is more efficient, is dispatched faster and is more cost-effective. These findings are highly relevant to other remote regions in Australia and internationally that have comparable GP-led retrieval services.


Subject(s)
Air Ambulances , Humans , Australia , Cost-Benefit Analysis , Referral and Consultation , Outcome Assessment, Health Care
3.
Elife ; 122023 Dec 08.
Article in English | MEDLINE | ID: mdl-38063302

ABSTRACT

The maintenance of the functional integrity of the intestinal epithelium requires a tight coordination between cell production, migration, and shedding along the crypt-villus axis. Dysregulation of these processes may result in loss of the intestinal barrier and disease. With the aim of generating a more complete and integrated understanding of how the epithelium maintains homeostasis and recovers after injury, we have built a multi-scale agent-based model (ABM) of the mouse intestinal epithelium. We demonstrate that stable, self-organizing behaviour in the crypt emerges from the dynamic interaction of multiple signalling pathways, such as Wnt, Notch, BMP, ZNRF3/RNF43, and YAP-Hippo pathways, which regulate proliferation and differentiation, respond to environmental mechanical cues, form feedback mechanisms, and modulate the dynamics of the cell cycle protein network. The model recapitulates the crypt phenotype reported after persistent stem cell ablation and after the inhibition of the CDK1 cycle protein. Moreover, we simulated 5-fluorouracil (5-FU)-induced toxicity at multiple scales starting from DNA and RNA damage, which disrupts the cell cycle, cell signalling, proliferation, differentiation, and migration and leads to loss of barrier integrity. During recovery, our in silico crypt regenerates its structure in a self-organizing, dynamic fashion driven by dedifferentiation and enhanced by negative feedback loops. Thus, the model enables the simulation of xenobiotic-, in particular chemotherapy-, induced mechanisms of intestinal toxicity and epithelial recovery. Overall, we present a systems model able to simulate the disruption of molecular events and its impact across multiple levels of epithelial organization and demonstrate its application to epithelial research and drug development.


Subject(s)
Intestinal Mucosa , Intestines , Mice , Animals , Cell Proliferation/physiology , Intestinal Mucosa/metabolism , Cell Differentiation/physiology , Homeostasis/physiology
4.
Nutrients ; 15(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37960183

ABSTRACT

Early life feeding practices may affect the long-term health of individuals, particularly in terms of the development of non-communicable diseases, such as metabolic and allergic diseases. Accumulating evidence suggests that the interplay of breastfeeding and/or formula feeding followed by the introduction of solids plays a role in the occurrence of non-communicable diseases both in the short and long term. International food allergy guidelines recommend that breastfeeding women do not need to avoid food allergens and do not recommend any infant formula for allergy prevention. Guidelines regarding solid food introduction for food allergy prevention recommend the introduction of well-cooked eggs and peanuts around 4-6 months of age, and not to delay the introduction of other food allergens. There is also an increasing trend to feed infants a plant-based or plant-forward diet and have access to infant formulas based on plant-based ingredients. The use of novel plant-based infant formulas raises a few questions reviewed in this paper: (1) Do fortified, plant-based infant formulas, compliant with US Food and Drug Administration (FDA) regulations and European Food Safety Authority (EFSA) (European) guidelines, support adequate infant growth? (2) Are plant-based infant formulas suitable for the management of cow's milk allergy? (3) Does feeding with novel, plant-based infant formulas increase the risk of food allergies to the food allergens they contain? (4) Does feeding infants plant-based food allergens in early life increase the risk of allergic and severe allergic reactions? The review of the literature indicated that (1) plant-based formulas supplemented with amino acids and micronutrients to comply with FDA regulations and EFSA guidelines, evaluated in sufficiently powered growth studies, can support adequate growth in infants; (2) currently available plant-based infant formulas are suitable for the management of CMA; (3) an early introduction and continuous intake of food allergens are more likely to prevent food allergies than to increase their risk; and (4) an early introduction of food allergens in young infants is safe.


Subject(s)
Food Hypersensitivity , Milk Hypersensitivity , Noncommunicable Diseases , Infant , Animals , Cattle , Humans , Female , Infant Formula/chemistry , Food Hypersensitivity/prevention & control , Milk Hypersensitivity/prevention & control , Breast Feeding , Allergens , Infant Food
5.
BMJ Open ; 13(5): e068762, 2023 05 25.
Article in English | MEDLINE | ID: mdl-37230525

ABSTRACT

INTRODUCTION: With technological advancement and the COVID-19 pandemic, paper-based media are giving way to screen-based media to promote healthy ageing. However, there is no review available covering paper and screen media use by older people, so the objective of this review is to map the current use of paper-based and/or screen-based media for health education aimed at older people. METHODS AND ANALYSIS: The literature will be searched in Scopus, Web of Science, Medline, Embase, Cinahl, The ACM Guide to Computing Literature and Psyinfo databases. Studies in English, Portuguese, Italian or Spanish published from 2012 to the date of the search will be examined. In addition, an additional strategy will be carried out, which will be a Google Scholar search, in which the first 300 studies according to Google's relevance algorithm will be verified. The terms used in the search strategy will be focused on older adults, health education, paper-based and screen-based media, preferences, intervention and other related terms. This review will include studies where the average age of the participants was 60 years or older and were users of health education strategies through paper-based or screen-based media. Two reviewers will carry out the selection of studies in five steps: identification of studies and removal of duplicates, pilot test, selection by reading titles and abstracts, full-text inclusion and search for additional sources. A third reviewer will resolve disagreements. To record information from the included studies, a data extraction form will be used. The quantitative data will be presented in a descriptive way and the qualitative data through Bardin's content analysis. ETHICS AND DISSEMINATION: Ethical approval is not applicable to the scoping review. The results will be disseminated through presentations at significant scientific events and published in journals in the area. PROTOCOL REGISTRATION NUMBER: Open science framework (DOI: DOI 10.17605/OSF.IO/GKEAH).


Subject(s)
COVID-19 , Humans , Aged , Middle Aged , COVID-19/epidemiology , Pandemics , Algorithms , Data Accuracy , Health Education , Research Design , Review Literature as Topic
6.
Cell Death Dis ; 14(4): 268, 2023 04 13.
Article in English | MEDLINE | ID: mdl-37055381

ABSTRACT

Galectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon cancer cells induces cancer cell secretion, in an autocrine/paracrine manner, of a number of proteases including cathepsin-B, MMP-1 and MMP-13. The secretion of these proteases causes disruption of epithelial monolayer integrity, increases its permeability and promotes tumour cell invasion. This effect of galectin-3 is shown to be mediated through induction of cellular PYK2-GSK3α/ß signalling and can be prevented by the presence of galectin-3 binding inhibitors. This study thus reveals an important mechanism in galectin-3-mediated promotion of cancer progression and metastasis. It provides further evidence to the increased realization of galectin-3 as a potential therapeutic target for the treatment of cancer.


Subject(s)
Colonic Neoplasms , Galectin 3 , Humans , Galectin 3/genetics , Galectin 3/metabolism , Peptide Hydrolases , Colonic Neoplasms/metabolism , Epithelium/metabolism
7.
Arch Bone Jt Surg ; 11(1): 53-63, 2023.
Article in English | MEDLINE | ID: mdl-36816354

ABSTRACT

Background: The Satisfaction and Recovery Index (SRI) is a generic importance-weighted health satisfaction tool to measure the process and state of recovery following musculoskeletal injuries. The objectives of this study are (1) to translate and cross-culturally adapt the SRI to Persian and (2) evaluate its psychometric properties. Methods: The forward-backward translation technique was used for translation, and two rounds of cognitive interviews were conducted to assess cultural appropriateness. Participants (n=100, mean age=32.5, 82%male) had acute (i.e., <30 days) musculoskeletal injuries of any etiology. Structural validity, construct validity, internal consistency, and test-retest reliability were evaluated. Results: Participants identified issues in 3/6 areas of a coding system during the cognitive interviews: comprehension/clarity, relevance, and inadequate response definition. These issues informed subsequent changes to arrive at the final version of the SRI-P. The SRI-P had adequate construct validity (P<0.001), the confirmatory factor analysis demonstrated a two-factor structure, the internal consistency was acceptable (Cronbach's α=0.83), and it was deemed reliable (ICC2, 1=0.72). Conclusion: The psychometric evaluation revealed that the SRI-P has adequate construct validity, internal consistency, and test-retest reliability. Unlike the original English version, the SRI-P has a two-factor structure, which appears to be related to cultural differences in interpreting some of the items. The clinical importance of this study is that the SRI (which captures the state of recovery and how important the various items of the tool are to each patient and how satisfied they are with their recovery) can now be available to surgeons and therapists in the orthopedic and rehabilitation realms in Persian populations.

8.
Aust J Rural Health ; 31(2): 322-335, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36484695

ABSTRACT

INTRODUCTION: In February 2018 the Remote Medical Practitioner (RMP)-led telehealth model for providing both primary care advice and aeromedical retrievals in Central Australia was replaced by the Medical Retrieval and Consultation Centre (MRaCC) and Remote Outreach Consultation Centre (ROCC). In this new model, specialists with advanced critical care skills provide telehealth consultations for emergencies 24/7 and afterhours primary care advice (MRaCC) while RMPs (general practitioners) provide primary care telehealth advice in business hours via the separate ROCC. OBJECTIVE: To evaluate changes in clinicians' perceptions of efficiency and timeliness of the new (MRaCC) and (ROCC) model in Central Australia. DESIGN: There were 103 and 72 respondents, respectively, to pre- and post-implementation surveys of remote clinicians and specialist staff. FINDINGS: Both emergency and primary care aspects of telehealth support were perceived as being significantly more timely and efficient under the newly introduced MRaCC/ROCC model. Importantly, health professionals in remote community were more likely to feel that their access to clinical support during emergencies was consistent and immediately available. DISCUSSION: Respondents consistently perceived the new MRaCC/ROCC model more favourably than the previous RMP-led model, suggesting that there are benefits to having separate referral streams for telehealth advice for primary health care and emergencies, and staffing the emergency stream with specialists with advanced critical care skills. CONCLUSION: Given the paucity of literature about optimal models for providing pre-hospital medical care to remote residents, the findings have substantial local, national and international relevance and implications, particularly in similar geographically large countries, with low population density.


Subject(s)
Remote Consultation , Telemedicine , Humans , Australia , Emergencies , Primary Health Care , Surveys and Questionnaires
9.
Cancers (Basel) ; 14(24)2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36551683

ABSTRACT

Therapies with the mechanistic target of rapamycin complex 1 (mTORC1) inhibitors are not fully curative for tuberous sclerosis complex (TSC) patients. Here, we propose that some mTORC1-independent disease facets of TSC involve signaling through redox factor-1 (Ref-1). Ref-1 possesses a redox signaling activity that stimulates the transcriptional activity of STAT3, NF-kB, and HIF-1α, which are involved in inflammation, proliferation, angiogenesis, and hypoxia, respectively. Here, we demonstrate that redox signaling through Ref-1 contributes to metabolic transformation and tumor growth in TSC cell model systems. In TSC2-deficient cells, the clinically viable Ref-1 inhibitor APX3330 was effective at blocking the hyperactivity of STAT3, NF-kB, and HIF-1α. While Ref-1 inhibitors do not inhibit mTORC1, they potently block cell invasion and vasculature mimicry. Of interest, we show that cell invasion and vasculature mimicry linked to Ref-1 redox signaling are not blocked by mTORC1 inhibitors. Metabolic profiling revealed that Ref-1 inhibitors alter metabolites associated with the glutathione antioxidant pathway as well as metabolites that are heavily dysregulated in TSC2-deficient cells involved in redox homeostasis. Therefore, this work presents Ref-1 and associated redox-regulated transcription factors such as STAT3, NF-kB, and HIF-1α as potential therapeutic targets to treat TSC, where targeting these components would likely have additional benefits compared to using mTORC1 inhibitors alone.

10.
BMJ Open ; 12(11): e066950, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36328388

ABSTRACT

INTRODUCTION: Peripheral arterial disease (PAD) is a key risk factor for cardiovascular disease, foot ulceration and lower limb amputation in people with diabetes. Early diagnosis of PAD can enable optimisation of therapies to manage these risks. Its diagnosis is fundamental, though challenging in the context of diabetes. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most accurate in routine clinical practice.The aim of this study is to determine the diagnostic performance of a variety of tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of PAD in people with diabetes as determined by a reference test (CT angiography (CTA) or magnetic resonance angiography (MRA)). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan). METHODS AND ANALYSIS: A prospective multicentre diagnostic accuracy study (ClinicalTrials.gov Identifier NCT05009602). We aim to recruit 730 people with diabetes from 18 centres across the UK, covering primary and secondary healthcare. Consenting participants will undergo the tests under investigation. Reference tests (CTA or MRA) will be performed within 6 weeks of the index tests. Imaging will be reported by blinded consultant radiologists at a core imaging lab, using a validated scoring system, which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ≥50% stenosis, or tandem lesions with a combined value of ≥50%, will be used as the threshold for the diagnosis of PAD. The primary outcome measure of diagnostic performance will be test sensitivity. ETHICS AND DISSEMINATION: The study has received approval from the National Research Ethics Service (NRES) (REC reference 21/PR/1221). Results will be disseminated through research presentations and papers. TRIAL REGISTRATION NUMBER: NCT05009602.


Subject(s)
Diabetes Mellitus , Peripheral Arterial Disease , Humans , Prospective Studies , Peripheral Arterial Disease/diagnosis , Ankle Brachial Index/adverse effects , Ultrasonography, Doppler, Duplex , Multicenter Studies as Topic
11.
Front Sports Act Living ; 4: 911412, 2022.
Article in English | MEDLINE | ID: mdl-36172339

ABSTRACT

Aim: This study aimed to explore athletes' experiences and opinions of communication strategies in applied sports nutrition, as well as capture suggestions for future mobile app supportive solutions. Methods: A qualitative approach was used for this research. Data was generated from semi-structured focus groups (n = 9) with a purposive sample of 41 (male = 24, female = 17) full time professional athletes (mean age 24 ± 4.59) from five sports (football, rugby union, athletics, cycling, and boxing). Data was analyzed using reflexive thematic analysis. Results: The analysis identified four higher order themes and five sub themes. Athletes appear dissatisfied with the levels of personalization in the nutrition support they receive. Limited practitioner contact time was suggested as a contributing factor to this problem. Athletes acknowledged the usefulness of online remote nutrition support and reported a desire for more personalized technology that can tailor support to their individual needs. Conclusion: Athletes experienced a hybrid human-computer approach that combines in-person and remote digital methods to communicate with and receive information from practitioners. Mobile technology may now afford sports nutritionists with new opportunities to develop scalable solutions to support practice.

12.
Cancers (Basel) ; 14(13)2022 Jul 03.
Article in English | MEDLINE | ID: mdl-35805035

ABSTRACT

Matrix metalloproteinase-13 (MMP-13) is a member of the Matrix metalloproteinases (MMPs) family of endopeptidases. MMP-13 is produced in low amounts and is well-regulated during normal physiological conditions. Its expression and secretion are, however, increased in various cancers, where it plays multiple roles in tumour progression and metastasis. As an interstitial collagenase, MMP-13 can proteolytically cleave not only collagens I, II and III, but also a range of extracellular matrix proteins (ECMs). Its action causes ECM remodelling and often leads to the release of various sequestered growth and angiogenetic factors that promote tumour cell growth, invasion and angiogenesis. This review summarizes our current understanding of the regulation of MMP-13 expression and secretion and discusses the actions of MMP-13 in cancer progression and metastasis.

13.
BMC Health Serv Res ; 22(1): 953, 2022 Jul 27.
Article in English | MEDLINE | ID: mdl-35897023

ABSTRACT

BACKGROUND: Prematurity is still the leading cause of global neonatal mortality, Rwanda included, even though advanced medical technology has improved survival. Initial hospitalization of premature babies (PBs) is associated with high costs which have an impact on Rwanda's health budget. In Rwanda, these costs are not known, while knowing them would allow better planning, hence the purpose and motivation for this research. METHODS: This was a prospective cost of illness study using a prevalence approach conducted in 5 hospitals (University Teaching Hospital of Butare, Gisenyi, Masaka, Muhima, and Ruhengeri). It included PBs admitted from June to July 2021 followed up prospectively to determine the medical direct costs (MDC) by enumerating the cost of all inputs. Descriptive analyses and ordinary least squares regression were used to illustrate factors associated with and predictive of mean cost. The significance level was set at p < 0.05. RESULTS: A total of 123 PBs were included. Very preterm and moderate PBs were 36.6% and 23.6% respectively and the average birth weight (BW) was 1724 g (SD: 408.1 g). The overall mean MDC was $237.7 per PB (SD: $294.9) representing 28% of Gross Domestic Product (GDP) per capita per year. Costs per PB varied with weight category, prematurity degree, hospital level, and length of stay (LoS) among other variables. MDC was dominated by drugs and supplies (65%) with oxygen being an influential driver of MDC accounting for 38.4% of total MDC. Birth weight, oxygen therapy, and hospital level were significant MDC predictive factors. CONCLUSION: This study provides an in-depth understanding of MDC of initial hospitalization of PBs in Rwanda. It also indicates predictive factors, including birth weight, which can be managed through measures to prevent or delay preterm birth. IMPLICATION FOR PREMATURITY PREVENTION AND MANAGEMENT: The results suggest a need to revise the benefits and entitlements of insured people to include drugs and interventions not covered that are essential and where there are no alternatives. Having oxygen plants in hospitals may reduce oxygen-related costs. Furthermore, interventions to reduce prematurity should be evaluated using cost-effectiveness analysis since its overall burden is high.


Subject(s)
Infant, Premature, Diseases , Premature Birth , Birth Weight , Cost of Illness , Cost-Benefit Analysis , Female , Hospitalization , Humans , Infant , Infant, Newborn , Oxygen , Prevalence , Prospective Studies , Rwanda/epidemiology , Uganda
14.
Genome Biol ; 23(1): 85, 2022 03 28.
Article in English | MEDLINE | ID: mdl-35346327

ABSTRACT

Determining the evolutionary relationships between genes is fundamental to comparative biological research. Here, we present SHOOT. SHOOT searches a user query sequence against a database of phylogenetic trees and returns a tree with the query sequence correctly placed within it. We show that SHOOT performs this analysis with comparable speed to a BLAST search. We demonstrate that SHOOT phylogenetic placements are as accurate as conventional tree inference, and it can identify orthologs with high accuracy. In summary, SHOOT is a fast and accurate tool for phylogenetic analyses of novel query sequences. It is available online at www.shoot.bio .


Subject(s)
Algorithms , Biological Evolution , Phylogeny
15.
Eur J Cancer ; 164: 39-51, 2022 03.
Article in English | MEDLINE | ID: mdl-35172272

ABSTRACT

BACKGROUND: Biomarkers for cyclin-dependent kinase 4/6 inhibitors, such as palbociclib, for patients with hormone receptor-positive/HER2-negative metastatic breast cancer are lacking. Thymidine kinase is a proliferation marker downstream of the cyclin-dependent kinase 4/6 pathway. We prospectively investigated the prognostic role of serum thymidine kinase activity (sTKa), in patients treated with Palbociclib + fulvestrant. PATIENTS AND METHODS: PYTHIA was a phase II, single-arm, multicentre, trial that enrolled 124 post-menopausal women with endocrine-resistant hormone receptor-positive/HER2-negative metastatic breast cancer. Serum samples were collected pre-treatment (pre-trt; n = 122), at day 15 of cycle 1 (D15; n = 108), during the one week-off palbociclib before initiating cycle 2 (D28; n = 108) and at end of treatment (n = 76). sTKa was determined centrally using Divitum®, a refined ELISA-based assay with a limit of detection of 20 Divitum Units (Du)/L. The primary study endpoint was progression-free survival, assessed for its association with pre- and on-treatment sTKa. RESULTS: Data from 122 women were analysed. Pre-treatment sTKa was not associated with clinical characteristics and moderately correlated with tissue Ki-67. Palbociclib + fulvestrant markedly suppressed sTKa levels at D15, with 83% of patients recording levels below limit of detection. At D28, sTKa showed a rebound in 60% of patients. At each timepoint, higher sTKa was associated with shorter progression-free survival (each p < 0.001), with the strongest effect at D15. CONCLUSIONS: STKa is an independent prognostic biomarker in patients treated with palbociclib. High pre-treatment sTKa and its incomplete suppression during treatment may identify patients with poorer prognosis and primary resistance. This warrants validation in prospective comparative trials. CLINICALTRIALS. GOV IDENTIFIER: NCT02536742; EudraCT 2014-005387-15.


Subject(s)
Breast Neoplasms , Thymidine Kinase , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cyclin-Dependent Kinase 4 , Female , Fulvestrant/therapeutic use , Humans , Male , Piperazines , Prospective Studies , Pyridines , Thymidine Kinase/therapeutic use
16.
Anal Chim Acta ; 1197: 339492, 2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35168723

ABSTRACT

A general and deterministic model is derived from the fundamentals of liquid chromatography to calculate retention time, peak width, peak capacity, and density of peak capacity in gradient liquid chromatography. The calculation of these chromatographic properties accounts for 1) the presence of initial (separation of the earliest eluters) and final (column wash) isocratic steps before and after the linear gradient, respectively, 2) the pre- (flow through needle and preheater tubes) and post-column (outlet and emitter tubes before MS detection) dispersion, 3) the compression of the chromatographic band, and 4) the retention of the organic modifier onto the RPLC column. The multiple and variable method parameters may include the column dimensions, particle size, flow rate, temperature, initial and final isocratic hold times, gradient time, gradient steepness, column conditioning/sample load time, and the pre- and post-column tube dimensions. The model enables the users to perform robust multi-dimensional optimization of UHPLC-MS methods and offers the possibility to predict the expected MS feature density for increased method performance. Method optimization can be further improved by matching the observed MS feature density (number of metabolites detected as function of time) to the predicted density of peak capacity. It is directly applied to the optimization of high-throughput RPLC separation methods specifically designed for large-scale urinary metabolic phenotyping.


Subject(s)
Metabolomics , Tandem Mass Spectrometry , Chromatography, Liquid , Particle Size , Pressure
17.
Transfus Med ; 32(3): 210-220, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34850464

ABSTRACT

BACKGROUND: All SCD patients need extended RBC antigen typing (by serology or genotyping) for provision of extended RH, K matched blood and to guide RBC selection in those with complex transfusion requirements. Genotyping can also identify RH variants which can cause sensitisation even when extended RH phenotypically matched blood is provided and alloantibodies associated with RH variants can cause HTRs. OBJECTIVES: To review the use of RBC genotyping in SCD patients at two London trusts (ICHNT, LNWH) with a focus on RH variants. METHODS: Retrospective review with data collected from clinical notes, local and national pathology reporting systems. RESULTS: A 311/482 (64%) ICHNT patients and 181/346 (52%) LNWH patients had extended genotyping. Of genotyped patients, 68 (22%) ICHNT and 31 (17%) LNWH patients had RH variants. Eight ICHNT patients had RH variants and corresponding antibodies associated with RH variants; 4/8 received multiple transfusions with antigen positive RBCs but had no evidence of haemolysis. One LNWH patient had a RH variant with corresponding alloantibody but could not be investigated further for possible HTR. CONCLUSIONS: Most patients (59%) had genotyping and a significant number had RH variants (99, 20%). A small proportion (9, 9%) had antibodies associated with RH variants, but with no evidence of clinically significant HTRs despite transfusions in four of them with antigen positive RBCs. All SCD patients should have RBC genotyping including RH variants (preferentially over extended phenotyping) to guide better selection of RBC units. However, where antigen negative blood cannot be provided, the risk of alloimmunisation is not inevitable and subsequent HTRs from antibodies associated with RH variants might not always occur.


Subject(s)
Anemia, Sickle Cell , Blood Grouping and Crossmatching , Anemia, Sickle Cell/genetics , Anemia, Sickle Cell/therapy , Erythrocytes , Genotype , Humans , Isoantibodies , London , Rh-Hr Blood-Group System
18.
Knee ; 33: 374-377, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34773791

ABSTRACT

Tears of the medial collateral ligament of the knee are common and often managed non-operatively [1]. Grade 3 tears that fail to heal are often treated with surgical repair through an open incision on the medial aspect of the knee. Many other ligament injuries of the knee are now managed with arthroscopic surgery. This has not yet been described for medial collateral ligament injuries of the knee. We describe a new arthroscopically assisted technique for MCL repair after grade III injury which avoids some of these complications.


Subject(s)
Anterior Cruciate Ligament Injuries , Medial Collateral Ligament, Knee , Arthroscopy , Humans , Knee Joint/diagnostic imaging , Knee Joint/surgery , Lower Extremity , Medial Collateral Ligament, Knee/diagnostic imaging , Medial Collateral Ligament, Knee/surgery
19.
BMJ Open ; 11(10): e052414, 2021 10 08.
Article in English | MEDLINE | ID: mdl-34625417

ABSTRACT

INTRODUCTION: Ageing is a natural process marked by physiological changes and declines in functional capacity. One strategy to encourage healthy habits in older people is the use of applications on mobile devices to promote physical activity (PA). An immediate challenge is for these applications to be accessible to older people themselves, while a second challenge is to retain their interest and engagement in connection with PA itself. Therefore, the purpose of this review is to map the factors related to the adoption and adherence of PA mobile applications by older people. METHODS AND ANALYSIS: Five databases will be searched where articles and reviews, available between 2010 and present, in English, Portuguese or Spanish, at full text, will be included. In addition, two additional strategies will be performed, including grey literature. The search terms adoption, adherence, factors, mobile application, PA, older people and other terms related to them will be used in the search strategy. This review will include studies that identify factors related to the adoption and adherence to PA mobile applications by people over 60 years. The selection of studies will be carried out by two reviewers in five stages: identification of studies and duplicate removal; pilot test; selection by reading abstracts; inclusion by reading the full text and search in additional sources. Disagreements will be resolved by a third reviewer. Data will be extracted using a data extraction tool. Quantitative data will be described in a narrative manner and qualitative data will be categorised through inductive thematic analysis. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review. Plans for the dissemination of the review include the presentation of the results at relevant scientific conferences and the submission and publication in significant journals.


Subject(s)
Mobile Applications , Text Messaging , Aged , Exercise , Humans , Research Design , Review Literature as Topic
20.
Women Health ; 61(9): 867-871, 2021 10.
Article in English | MEDLINE | ID: mdl-34569446

ABSTRACT

Metastatic spread of invasive lobular breast carcinoma to stomach is rare especially before diagnosis of primary breast cancer. Incorrect diagnosis might result in delay of appropriate treatment for breast cancer. Recognition of this possibility enables better clinical management. A 62-year-old female presented with upper gastrointestinal symptoms and weight loss and was referred to a gastroenterologist for investigation. At the time of initial diagnosis of stomach cancer, patient was asymptomatic for breast cancer. Multiple gastric biopsies taken showed features suspicious of metastatic breast cancer. Consequently, the initial provisional diagnosis of stomach cancer changed into metastatic invasive lobular breast carcinoma. These findings were corroborated radiologically. The patient was treated with letrozole and zoledronic acid as first-line therapy for one year. Residual metastatic breast cancer was present in the gastric mucosa. The patient was treated with endocrine therapy containing ribociclib and treatment was ineffective confirmed by PET-CT scan. But her symptoms have resolved completely despite her presentation with stage IV. We present rare case of initial presentation of gastric metastasis before diagnosis of a primary invasive lobular breast carcinoma. Correct diagnosis and appropriate treatment were accomplished through initial clinical suspicion, accurate histological examination, and endoscopy together with analysis of disease-specific biomarkers.


Subject(s)
Breast Neoplasms , Carcinoma, Lobular , Breast Neoplasms/diagnosis , Carcinoma, Lobular/diagnostic imaging , Female , Humans , Middle Aged , Pakistan , Positron Emission Tomography Computed Tomography , Stomach
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