Enhancing clinical decision support with genomic tools in breast cancer: A Scottish perspective.

INTRODUCTION: The Oncotype DX Breast RS test has been adopted in Scotland and has been the subject of a large population-based study by a Scottish Consensus Group to assess the uptake of the recurrence score (RS), evaluate co-variates associated with the RS and to analyse the effect it may have had on clinical practice. MATERIALS & METHODS: Pan-Scotland study between August 2018-August 2021 evaluating 833 patients who had a RS test performed as part of their diagnostic pathway. Data was extracted retrospectively from electronic records and analysis conducted to describe change in chemotherapy administration (by direct comparison with conventional risk assessment tools), and univariate/multivariate analysis to assess relationship between covariates and the RS. RESULTS: Chemotherapy treatment was strongly influenced by the RS (p < 0.001). Only 30 % of patients received chemotherapy treatment in the intermediate and high risk PREDICT groups, where chemotherapy is considered. Additionally, 55.5 % of patients with a high risk PREDICT had a low RS and did not receive chemotherapy. There were 17 % of patients with a low risk PREDICT but high RS who received chemotherapy. Multivariate regression analysis showed the progesterone receptor Allred score (PR score) to be a strong independent predictor of the RS, with a negative PR score being associated with high RS (OR 4.49, p < 0.001). Increasing grade was also associated with high RS (OR 3.81, p < 0.001). Classic lobular pathology was associated with a low RS in comparison to other tumour pathology (p < 0.01). Nodal disease was associated with a lower RS (p = 0.012) on univariate analysis, with menopausal status (p = 0.43) not influencing the RS on univariate or multivariate analysis. CONCLUSIONS: Genomic assays offer the potential for risk-stratified decision making regarding the use of chemotherapy. They can help reduce unnecessary chemotherapy treatment and identify a subgroup of patients with more adverse genomic tumour biology. A recent publication by Health Improvement Scotland (HIS) has updated guidance on use of the RS test for NHS Scotland. It suggests to limit its use to the intermediate risk PREDICT group. Our study shows the impact of the RS test in the low and high risk PREDICT groups. The implementation across Scotland has resulted in a notable shift in practice, leading to a significant reduction in chemotherapy administration in the setting of high risk PREDICT scores returning low risk RS. There has also been utility for the test in the low risk PREDICT group to detect a small subgroup with a high RS. We have found the PR score to have a strong independent association with high risk RS. This finding was not evaluated by the key RS test papers, and the potential prognostic information provided by the PR score as a surrogate biomarker is an outstanding question that requires more research to validate.

Noninvasive measurement of tracer extraction efficiency in tissue, illustrated with Tc-99m-MAG3.

OBJECTIVE: The aim of this study is to develop a noninvasive technique for measuring tissue tracer extraction efficiency ( E ) and illustrate it for Tc-99m-mercaptoacetyltriglycine (MAG3) and kidney. METHODS: E was measured in 10 patients with normal MAG3 renography. E is the ratio of tissue clearance-to-blood flow ( Ki/F ). For single-photon tracers, attenuation constants are unknown, so Ki and F cannot be separately measured. However, by deriving attenuation-uncorrected Ki' and F' from the same regions of interests (ROIs), these constants cancel out, giving E . Using a lung ROI for blood activity, F was measured from first-pass and Ki' from Gjedde-Patlak-Rutland (GPR) analysis up to 130 s. Because of interference from right ventricle, a left ventricular ROI (LV) is unsuitable for F' but was used in GPR analysis, making an adjustment for the ratio of respective blood pool signals arising from lung and LV ROIs in early frames (60-90 s). RESULTS: A lung ROI underestimates F' by 4% at normal LV function. Chest wall interstitial activity ( I ), which does not affect F' , amounted to 53 and 30% of the lung and LV signals at 20 min, and 12 and 6% at 130 s, resulting in underestimations of Ki of 4 and 2%, respectively. Ignoring these opposing errors, E based on lung ROI for left and right kidneys was 43.5 (SD 8)% and 47.3 (9)%, and based on LV ROI for GPR analysis was 44.5 (10.9)% and 48.3 (10.6)%. CONCLUSION: E can be measured by combining blood flow from first-pass with clearance from GPR analysis, and has potential value both clinically and in clinical research.

Association of the habitual dietary intake with the fatty liver index and effect modification by metabotypes in the population-based KORA-Fit study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging threat for public health with diet being a major risk factor in disease development and progression. However, the effects of habitual food consumption on fatty liver are still inconclusive as well as the proposed role of the individuals' metabolic profiles. Therefore, the aim of our study is to examine the associations between diet and NAFLD with an emphasis on the influence of specific metabotypes in the general population. METHODS: A total of 689 participants (304 men and 385 women) of the KORA-Fit (S4) survey, a follow-up study of the population-based KORA cohort study running in the Region of Augsburg, Germany, were included in this analysis. Dietary information was derived from repeated 24-h food lists and a food frequency questionnaire. The intake of energy and energy-providing nutrients were calculated using the national food composition database. The presence of fatty liver was quantified by the fatty liver index (FLI), and metabotypes were calculated using K-means clustering. Multivariable linear regression models were used for the analysis of habitual food groups and FLI; for the evaluation of macronutrients, energy substitution models were applied. RESULTS: A higher consumption of nuts and whole grains, and a better diet quality (according to Alternate Healthy Eating Index and Mediterranean Diet Score) were associated with lower FLI values, while the intake of soft drinks, meat, fish and eggs were associated with a higher FLI. The isocaloric substitution of carbohydrates with polyunsaturated fatty acids was associated with a decreased FLI, while substitution with monounsaturated fatty acids and protein showed increased FLI. Statistically significant interactions with the metabotype were observed for most food groups. CONCLUSION: The consumption of plant-based food groups, including nuts and whole grains, and diet quality, were associated with lower FLI values, whereas the intake of soft drinks and products of animal origin (meat, fish, eggs) were associated with a higher FLI. The observed statistically significant interactions with the metabotype for most food groups could help to develop targeted prevention strategies on a population-based level if confirmed in independent prospective studies.

The UK Divide: Does Having a Pembrolizumab-Chemotherapy Option in Head and Neck Cancer Matter? Real-world Experience of First-line Palliative Pembrolizumab Monotherapy and Pembrolizumab-Chemotherapy Combination in Scotland.

AIMS: The Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence, who approved monotherapy alone in England and Wales. The aim of this study was to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma in the palliative setting in Scotland. MATERIALS AND METHODS: We analysed the electronic records of patients who started pembrolizumab-containing treatment between 1 March 2020 and 30 September 2021. Outcomes included overall survival, progression-free survival (PFS), the duration of response and the disease control rate. Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival. RESULTS: Our cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to those in the KEYNOTE-048 study, although our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease. For patients receiving monotherapy (n = 76), 12- and 24-month overall survival were 45% and 27%, respectively. For patients receiving pembrolizumab-chemotherapy (n = 15), 12-month overall survival was 60% (24-month overall survival had not yet been reached). Experiencing one or more immune-related adverse event (irAE; versus no irAEs), of any grade, was associated with favourable overall survival and PFS for patients receiving monotherapy in both univariable Log-rank analysis (median overall survival 17.4 months versus 8.6 months, respectively, P = 0.0033; median PFS 10.9 months versus 3.0 months, respectively, P < 0.0001) and multivariable analysis (Cox proportional hazards regression: overall survival hazard ratio 0.31, P = 0.0009; PFS hazard ratio 0.17, P < 0.0001). CONCLUSION: Our real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show that irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing that irAEs are generally a positive marker of programmed death-ligand 1 (PD-L1) inhibitor response.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Clinical Experience of Axillary Radiotherapy for Node-positive Breast Cancer.

AIMS: Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. MATERIALS AND METHODS: We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan-Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. RESULTS: Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20-0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45-14.0, P = 0.009). CONCLUSION: We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology.

Errors in measurement of glomerular filtration rate using the slope-intercept technique and their identification.

BACKGROUND: GFR measured from plasma sampling may be expressed as slope-intercept GFR (SI-GFR) and scaled to body surface area (mGFR/BSA) or as GFR per unit extracellular fluid volume (mGFR/ECV), which is based only on half-time. Measurement errors comprise 3 categories. Pre-injection error arises from error in administered marker and is suspected when mGFR/BSA and mGFR/ECV disagree. Injection errors include 'tissued' injections. Post-injection errors include inaccurate sample timing, inaccurate pipetting, sample haemolysis and sampling through long IV lines through which marker was administered. The aim of the study was to evaluate the impact of errors on mGFR. METHODS: We compared mGFR/BSA with mGFR/ECV in 898 patients undergoing routine investigation. To investigate post-injection error, we took two further patient datasets with r values (correlation coefficient of the 3-sample fit) of 1.0 and introduced errors, in isolation, into each of the 3 recorded sample values, as follows: pipetting (volume) errors of -20%, -10%, -5%, 5%, 10% and 20%, and timing errors of -15 min, -10 min, -5 min, 5 min, 10 min and 15 min. RESULTS: The correlation between mGFR/BSA and mGFR/ECV was close and independent of r. Post-injection error depended on the time of the sample in which it occurred. r correlated poorly with error magnitude for both volume and timing errors. When a 'rogue' sample is suspected its error needed to be substantial for it to be identified by single sample estimates applied to the other samples. CONCLUSION: SI-GFR is resistant to post-injection timing and volume errors but not to pre-injection error.

Coherent charge oscillations in a bilayer graphene double quantum dot.

The coherent dynamics of a quantum mechanical two-level system passing through an anti-crossing of two energy levels can give rise to Landau-Zener-Stückelberg-Majorana (LZSM) interference. LZSM interference spectroscopy has proven to be a fruitful tool to investigate charge noise and charge decoherence in semiconductor quantum dots (QDs). Recently, bilayer graphene has developed as a promising platform to host highly tunable QDs potentially useful for hosting spin and valley qubits. So far, in this system no coherent oscillations have been observed and little is known about charge noise in this material. Here, we report coherent charge oscillations and [Formula: see text] charge decoherence times in a bilayer graphene double QD. The charge decoherence times are measured independently using LZSM interference and photon assisted tunneling. Both techniques yield [Formula: see text] average values in the range of 400-500 ps. The observation of charge coherence allows to study the origin and spectral distribution of charge noise in future experiments.

Quantitative lymphoscintigraphy of the lower limbs for the diagnosis of phlebolymphoedema.

INTRODUCTION: Phlebolymphoedema is caused by the interaction of the venous and lymphatic systems in a state of chronic venous insufficiency in which increased microvascular filtration causes an increased rate of lymph production. Lymphatic drainage rate increases in response, but this is unsustainable and can cause lymphatic failure and oedema. We hypothesise that in phlebolymphoedema we could measure unusually high lymphatic drainage while the lymph system is still fully functional. METHOD: Patients referred for lymphoscintigraphic investigation of swollen legs between April 2021 and December 2022 were reviewed. Quantitative lymphoscintigraphy was performed following the technique of Keramida et al . (2017) and ilio-inguinal nodal uptake (IIQ%) was calculated. The presence of scintigraphic features of increased lymph production was noted for each limb. RESULTS: A total of 39 patients were reviewed (78 limbs, 29F, 10M). Seven limbs were identified with supranormal lymphatic function (IIQ > 30%) plus three borderline. Of these 10 limbs, all had at least two scintigraphic features of increased lymph production. CONCLUSION: Quantitative lymphoscintigraphy, although developed for diagnosing abnormally low lymphatic function, may also have utility at the upper end of the spectrum for identifying chronic venous insufficiency. An IIQ% upper normal limit of 30% could be used to diagnose venous insufficiency as the cause for limb swelling. This is of note for patients of large body habitus in whom venous ultrasound is difficult.

Post-synthetic benzylation of the mRNA 5' cap via enzymatic cascade reactions.

mRNAs are emerging modalities for vaccination and protein replacement therapy. Increasing the amount of protein produced by stabilizing the transcript or enhancing translation without eliciting a strong immune response are major steps towards overcoming the present limitations and improving their therapeutic potential. The 5' cap is a hallmark of mRNAs and non-natural modifications can alter the properties of the entire transcript selectively. Here, we developed a versatile enzymatic cascade for regioselective benzylation of various biomolecules and applied it for post-synthetic modification of mRNA at the 5' cap to demonstrate its potential. Starting from six synthetic methionine analogues bearing (hetero-)benzyl groups, S-adenosyl-l-methionine analogues are formed and utilized for N7G-cap modification of mRNAs. This post-synthetic enzymatic modification exclusively modifies mRNAs at the terminal N7G, producing mRNAs with functional 5' caps. It avoids the wrong orientation of the 5' cap-a problem in common co-transcriptional capping. In the case of the 4-chlorobenzyl group, protein production was increased to 139% during in vitro translation and to 128-150% in four different cell lines. This 5' cap modification did not activate cytosolic pathogen recognition receptors TLR3, TLR7 or TLR8 significantly more than control mRNAs, underlining its potential to contribute to the development of future mRNA therapeutics.

[Intra-abdominal vascular injuries after blunt abdominal trauma]. / Intraabdominelle Gefäßverletzungen nach stumpfem Bauchtrauma.

Vascular injuries and hemorrhaging are serious potential complications in the management of patients with blunt abdominal trauma. The treatment depends on the extent and localization and can range from surveillance to endovascular treatment up to open surgery. The keys to success include the focused assessment with sonography for trauma (FAST) management and timely decision making. Abdominal vascular trauma continues to be a difficult problem and open and endovascular techniques continue to evolve in order to address this complex disease process.

Evaluating the effect of calcium, magnesium and sodium supplementation of Merino ewes on their lambs' growth.

Our study aimed to investigate responses to supplementation of calcium (Ca), magnesium (Mg) and sodium (Na) to lactating ewes and lambs grazing barley forage from lamb marking to weaning. A 10-ha paddock sown to barley was subdivided into eight plots as four replicates of two treatments. Merino ewes (n = 104) with lambs at foot were stratified to the eight plots (13 ewes and 21 lambs/plot) based on number of lambs (twin or single) and ewes' weight. Supplemented groups had access to mineral supplements (30 g/ewe/day) supplying 12 g/ewe/day ground limestone, 12 g/ewe/day Causmag® and 6 g/ewe/day coarse salt in a ratio of 2: 2: 1 by weight (as fed) from day 0 (a day before lamb marking) after sample collection. Control groups were not supplemented with minerals. Blood, milk and urine samples from ewes and blood from lambs were collected at different time points, namely, a day prior to lamb marking (day 0), 14 days after the commencement of study (day 14), and 28 days after the commencement of study (day 28). Weight of the lambs was also recorded at each time point. We found that the concentration of the forage minerals (Ca, Mg and potassium (K)) was lower on day 28 than on day 0 (P < 0.025). Liveweight gain was greater in the first 14 days compared with the second weight gain period (P < 0.001). The interaction of time and treatment was significant for liveweight (P < 0.001). Due to the improvement in weight gain of supplemented lambs, we recommend that mineral supplementation during late lactation is beneficial considering the low cost of minerals, even though the mineral content of the forage was not deficient.

Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Sexual dysfunction related to psychiatric disorders: a systematic review.

BACKGROUND: Sexual dysfunction is thought to be highly prevalent in patients with psychiatric disorders. Factors such as the use of psychotropic substances (ie, psychopharmaceuticals and drugs), age, or somatic diseases may contribute to sexual problems, but the extent to which psychopathology itself affects sexual functioning is not well understood. AIM: The study sought to provide an overview of the literature on the prevalence of sexual dysfunction in psychotropic-free and somatic disease-free psychiatric patients. METHOD: A systematic review (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) was conducted by 2 authors (TH and AWMP) independently, with the review process being monitored by a third author. Relevant articles on the relationship between sexual dysfunctions and psychopathology were searched in PubMed, Web of Science, and PsycINFO from inception until June 16, 2022. The study methods were entered in the international register of systematic reviews PROSPERO (2021, CRD42021223410). OUTCOMES: The main outcome measures were sexual dysfunction and sexual satisfaction. RESULTS: Twenty-four studies were identified, including a total of 1199 patients. These studies focused on depressive disorders (n = 9 studies), anxiety disorders (n = 7), obsessive- compulsive disorder (OCD) (n = 5), schizophrenia (n = 4), and posttraumatic stress disorder (n = 2). No studies on bipolar disorder were found. Reported prevalence rates of sexual dysfunction in psychiatric disorders were 45% to 93% for depressive disorders, 33% to 75% for anxiety disorders, 25% to 81% for OCD, and 25% for schizophrenia. The most affected phase of the sexual response cycle was sexual desire, in both men and women with depressive disorders, posttraumatic stress disorder, and schizophrenia. Patients with OCD and anxiety disorders most frequently reported dysfunction in the orgasm phase, 24% to 44% and 7% to 48%, respectively. CLINICAL IMPLICATIONS: The high prevalence of sexual dysfunction requires more clinical attention by means of psychoeducation, clinical guidance, sexual anamnesis, and additional sexological treatment. STRENGTHS AND LIMITATIONS: This is the first systematic review on sexual dysfunction in psychotropic-free and somatic disease-free psychiatric patients. Limitations include the small number of studies, small sample sizes, the use of multiple questionnaires (some not validated), which may contribute to bias. CONCLUSION: A limited number of studies identified a high prevalence of sexual dysfunction in patients with a psychiatric disorder, with substantial variation between patient groups in frequency and phase of reported sexual dysfunction.

Data-driven investment and performance management in the livestock sector.

Evidence-based decision-making is now axiomatic in many sectors and has become increasingly important in prioritising development in low- and middle-income countries. In the livestock development sector, there has been a lack of data on health and production required to establish an evidence base. Thus, much strategic and policy decision-making has been based on the more subjective grounds of opinion, expert or otherwise. However, there is now a trend towards a more data-driven approach for such decisions. The Centre for Supporting Evidence-Based Interventions in Livestock was established in Edinburgh by the Bill and Melinda Gates Foundation in 2016, to collate and publish livestock health and production data, lead a community of practice to harmonise livestock-data-related methodologies, and develop and monitor performance indicators for livestock investments.

La prise de décision fondée sur des données probantes est désormais une évidence pour de nombreux secteurs, et elle devient de plus en plus importante dans la priorisation des initiatives de développement dans les pays à revenus faibles et intermédiaires. Dans le secteur du développement de l'élevage, peu de données sont disponibles concernant la santé et la production animales, or ces éléments sont nécessaires pour établir une base de données probantes. De nombreuses décisions politiques et stratégiques sont donc prises sur la base d'éléments plus subjectifs - opinions d'experts ou autres. On observe cependant une tendance en faveur d'une approche davantage ancrée dans les données pour ce type de décisions. Le Centre for Supporting Evidence-Based Interventions in Livestock [Centre de soutien aux interventions basées sur des données probantes dans le domaine de l'élevage] a été établi par la Fondation Bill et Melinda Gates en 2016 à édinbourg. Il a pour objectif de rassembler et de publier les données relatives à la production et à la santé du bétail, d'animer une communauté de pratiques en vue d'harmoniser les méthodologies relatives aux données sur le bétail et d'élaborer et de superviser les indicateurs de performance utilisés pour orienter les investissements dans le secteur de l'élevage.

La adopción de decisiones atendiendo a datos y criterios factuales, algo que ya es un axioma en muchos sectores, ha venido cobrando creciente importancia a la hora de fijar prioridades de desarrollo en los países de renta baja o de renta media. En el sector pecuario han faltado los datos de sanidad y de producción necesarios para establecer una sólida base factual. De ahí que buena parte de los procesos decisorios de carácter estratégico y normativo hayan discurrido por el terreno más subjetivo de las opiniones, ya provengan estas de expertos o de cualquier otro ámbito. Ahora, sin embargo, se tiende cada vez más a tratar de adoptar este tipo de decisiones a partir de una base más objetiva. En 2016, la Fundación Bill y Melinda Gates estableció en Edimburgo el Centre for Supporting Evidence-Based Interventions in Livestock [Centro de apoyo a las intervenciones basadas en datos factuales en ganadería], cuyos objetivos se cifran en reunir y publicar datos de sanidad y producción pecuarias, encabezar una dinámica de praxis colectiva para armonizar los métodos referidos a los datos de la ganadería y elaborar y seguir de cerca los indicadores de rendimiento utilizados para orientar las inversiones en el sector pecuario.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

[Results of a single center vascular screening program in Germany]. / Ergebnisse eines monozentrischen Gefäßscreeningprogramms in Deutschland.

BACKGROUND: Cardiovascular diseases are the main cause of death in Europe with a relevant socioeconomic burden. A screening program for vascular diseases in asymptomatic persons with a defined risk constellation can lead to an early diagnosis. OBJECTIVE: The study examined a screening program for carotid stenosis, peripheral arterial occlusive disease (PAOD) and abdominal aortic aneurysms (AAA) in persons without any known vascular disease with respect to demographic data, risk factors, pre-existing conditions, medication intake, detection of pathological findings and/or findings requiring treatment. MATERIAL AND METHODS: Test subjects were invited using various information material and filled in a questionnaire on cardiovascular risk factors. The screening took place with measurement of the ABI and duplex sonography as a monocentric prospective single arm study within 1 year. Endpoints were the prevalence of risk factors and pathological and/or results requiring treatment. RESULTS: A total of 391 persons participated, 36% presented with at least 1 cardiovascular risk factor, 35.5% with 2 and 14.4% with 3 or more. The sonography showed results requiring control with a carotid stenosis of < 50-> 75% or occlusion in 9%. An AAA with a diameter of 3.0-4.5 cm was diagnosed in 0.9% and a pathological ABI < 0.9 or > 1.3 in 12.3%. The indications for a pharmacotherapy were found in 17% and no operation was recommended. CONCLUSION: The practicability of a screening program for carotid stenosis, PAOD and AAA of a defined risk population was shown. Vascular pathologies that required treatment were hardly found in the catchment area of the hospital. Consequently, the implementation of this screening program in Germany based on the collected data cannot currently be recommended in this form.

Sex-specific associations between systolic, diastolic and pulse pressure and hemostatic parameters in the population-based KORA-Fit study: a cross-sectional study.

BACKGROUND: Several prior studies postulated an effect of hypertension on coagulation factors. However, population-based studies investigating the sex-specific associations between hypertension and hemostatic parameters are scarce. Therefore, we investigated the relationship between blood pressure and parameters of coagulation, namely activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen, factor VIII, antithrombin III, protein C, protein S, and D-dimer in men and women from the general population. METHODS: Based on 803 participants (376 men, 427 women) from the KORA-Fit Study the sex-specific relationship between systolic, diastolic, and pulse pressure and commonly measured coagulation factors were investigated using multivariable-adjusted linear regression models. RESULTS: Hypertensive males had significantly higher median fibrinogen levels and factor VIII activity in comparison to normotensive males. There was a statistically significant difference between females with and without hypertension regarding the parameter fibrinogen, D-dimers, Protein S activity, and factor VIII activity. In multivariable linear regression analyses no significant association between systolic blood pressure, diastolic blood pressure, as well as pulse pressure and the investigated hemostatic parameters was found in men. In women, a significant positive association could be observed between systolic blood pressure and D-dimer level [ß-estimate per mmHg increase 3.37 (95% CI 0.935-5.804; p = 0.007)] and between pulse pressure and D-dimer level [ß-estimate per mmHg increase 5.351 (95% CI 1.772-8.930; p = 0.003)]. CONCLUSIONS: It appears that sex differences exist in the association between blood pressure parameters and commonly measured coagulation markers in the general population. Further studies are needed to identify the underlying causes.

The effects of facioscapulohumeral dystrophy and dynamic arm support on upper extremity muscle coordination in functional tasks.

This study's objective is to understand the effect of muscular weakness in persons with facioscapulohumeral dystrophy as well as the effect of a dynamic arm support on muscle coordination and activity performance, during activities of daily living. People with facioscapulohumeral dystrophy (n=12, 56.0±14.5 years) and healthy controls (n=12, 55.5±13.4 years) performed five simulated daily activity tasks, while unsupported and supported by the Gowing dynamic arm support. Surface electromyography, kinematics, and maximum force output were recorded. Outcomes were calculated for muscle coordination (muscle synergies), maximum muscle activity, movement performance indicators, and upper limb muscular weakness (maximum force output). Muscle coordination was altered and less consistent in persons with facioscapulohumeral dystrophy compared with healthy controls. The dynamic arm support alleviated muscle efforts and affected muscle coordination in both populations. While populations became more similar, the internal consistency of persons with facioscapulohumeral dystrophy remained unaffected and lower than that of healthy controls. Furthermore, the support affected movements' performance in both groups. The maximum force outputs were lower in persons with facioscapulohumeral dystrophy than controls. Muscle coordination differences were presumably the result of individual-specific in muscle weakness and compensatory strategies for dealing with gravity compensation and movement constraints.

Anterior-wall and non-anterior-wall STEMIs do not differ in long-term mortality: results from the augsburg myocardial infarction registry.

Background: Different ST-segment elevation myocardial infarction (STEMI) localizations go along with dissimilarities in the size of the affected myocardium, the causing coronary vessel occlusion, and the right ventricular participation. Therefore, this study aims to clarify if there is any difference in long-term survival between anterior- and non-anterior-wall STEMI. Methods: This study included 2,195 incident STEMI cases that occurred between 2009 and 2017, recorded by the population-based Augsburg Myocardial Infarction Registry, Germany. The study population comprised 1.570 men and 625 women aged 25-84 years at acute myocardial infarction. The patients were observed from the day of their first acute event with an average follow-up period of 4.3 years, (standard deviation: 3.0). Survival analyses and multivariable Cox regression analyses were performed to examine the association between infarction localizations and long-term all-cause mortality. Results: Of the 2,195 patients, 1,118 had an anterior (AWS)- and 1,077 a non-anterior-wall-STEMI (NAWS). No significant associations of the STEMI localization with long-term mortality were found. When comparing AWS with NAWS, a hazard ratio of 0.91 [95% confidence interval: 0.75-1.10] could be calculated after multivariable adjustment. In contrast to NAWS, AWS was associated with a greater <28 day mortality, less current or former smoking and higher creatine kinase-myocardial band levels (CK-MB) and went along with a higher frequency of impaired left ventricular ejection fraction (<30%). Conclusions: Despite pathophysiological differences between AWS and NAWS, and identified differences in multiple clinical characteristics, no significant differences in long-term mortality between both groups were observed.