Comparing visual and automated urine dipstick analysis in a general practice population

IntroductionUrinary symptoms constitute the primary reason for female patients to consult their general practitioner. The urinary dipstick test serves as a cornerstone for diagnosing urinary tract infections (UTIs), yet traditional visual interpretation may be subject to variability. Automated devices for dipstick urinalysis are routinely used as alternatives, yet the evidence regarding their accuracy remains limited. Therefore we aimed to compare concordance between visual and automated urinary dipstick interpretation and determine their test characteristics for the prediction of bacteriuria.Material and methodsWe conducted a prospective validation study including urine samples originating from adult patients in general practice that were sent to the Maastricht Medical Centre + for urinary culture. Urinary dipstick tests were performed on each sample, which were interpreted visually and automatically. We calculated Cohen's kappa and percentage agreement and used 2 x 2 tables to calculate test characteristics.ResultsWe included 302 urine samples. Visual and automated analysis showed almost perfect agreement (kappa = 0.82 and kappa = 0.86, respectively) for both nitrite and leukocyte esterase, but moderate agreement for erythrocytes (kappa = 0.51). Interpretation of clinically relevant (nitrite and/or leukocyte esterase positive) samples showed almost perfect agreement (kappa = 0.88). Urinary dipsticks show similar test characteristics with urinary culture as gold standard, with sensitivities of 0.92 and 0.91 and specificities of 0.37 and 0.41 for visual and automated interpretation respectively.ConclusionAutomated and visual dipstick analysis show near perfect agreement and perform similarly in predicting bacteriuria. However, automated analysis requires maintenance and occasionally measurement errors can occur

Cardiac (tele)rehabilitation in routine clinical practice for patients with coronary artery disease:protocol of the REHAB

Introduction Cardiac rehabilitation programs face the challenge of suboptimal participation, despite being a level Ia recommendation. Cardiac telerehabilitation, with its potential to engage patients who might otherwise not show interest, necessitates the adaption of existing center-based cardiac rehabilitation programs to facilitate rehabilitation at home. REHAB + is a mobile cardiac telerehabilitation program cocreated with patients and rehabilitation centers, aiming to future-proof cardiac rehabilitation and improve accessibility. The REHAB + application enables users to remotely communicate with their coach, receive on-demand feedback on health goal progression, and reduces the need for frequent in-person meetings at the cardiac rehabilitation center. The REHAB + study seeks to compare patient-related outcomes and characteristics of patients between those offered the option to participate in cardiac telerehabilitation and those attending center-based cardiac rehabilitation over a twelve-month period.Methods The REHAB + study is a multicenter, prospective, matched controlled, observational study that includes (N)STEMI patients eligible for cardiac rehabilitation. We aim to enroll 300 participants for cardiac telerehabilitation and 600 for center-based cardiac rehabilitation. Participants opting for cardiac telerehabilitation (REHAB+) will be matched with center-based cardiac rehabilitation participants. Additionally, characteristics of patients unwilling to participate in either center-based rehabilitation or telerehabilitation but are willing to share their demographics will be collected. The primary endpoint is quality of life measured with the SF-36 questionnaire at three and twelve months, with patient-related characteristics driving intervention choice as the most important secondary endpoint. Secondary endpoints include physical activity, modifiable risk factors, and digital health experience. The trial is registered at clinicaltrials.gov with registration number NCT05207072.Discussion The REHAB + trial is unique by offering patients freedom to choose between cardiac telerehabilitation and center-based rehabilitation. The integration of digital components into cardiac rehabilitation has the potential to complement behavioral change strategies for specific patient groups. Offering patients the option of cardiac telerehabilitation next to center-based rehabilitation could enhance overall cardiac rehabilitation participation rates

High-density and high-coverage composite atrial activation maps:an in-silico validation study

Objective: Repetitive atrial activation patterns (RAAPs) during complex atrial tachycardia could be associated with localized mechanisms that can be targeted. Clinically available electroanatomical mapping systems are limited by either the spatial coverage or electrode density of the mapping catheters, preventing the adequate visualization of transiently occurring RAAPs. This work proposes a technique to overcome this shortcoming by stitching spatially overlapping conduction patterns together to a larger image- called a composite map. Methods: Simulated stable mechanisms and meandering reentries are sequentially mapped (4x4 grid, 3mm spacing) and then reconstructed back to the original sizes with the proposed recurrence plot-based algorithm. Results: The reconstruction of single linear waves presents minimal errors (local activation time (LAT) difference: 3.2 [1.6-4.9] ms, conduction direction difference: 5.2 [2.3-8.0] degrees). Errors significantly increase (p&amp;lt;0.05) for more complex patterns, being the highest with unstable reentries (LAT difference: 10.3 [3.5-16.2] ms, conduction direction difference: 18.2 [6.7-29.7] deg). In a second part of the analysis, 111 meandering reentries are reconstructed. Mapping 30 locations overlappingly around each reentry core was found to be the optimal mapping strategy. For this optimal setting, LAT, conduction direction, and core localization errors are low (6.1 [4.2-8.6] ms, 11.2 [8.6-15.5] deg and 4.1 [2.9-4.9] mm, respectively) and are weakly correlated with the degree of the meander (&lt;inline-formula&gt;&lt;tex-math notation="LaTeX"&gt;$\rho$&lt;/tex-math&gt;&lt;/inline-formula&gt;=0.41, &lt;inline-formula&gt;&lt;tex-math notation="LaTeX"&gt;$\rho$&lt;/tex-math&gt;&lt;/inline-formula&gt;=0.40 and &lt;inline-formula&gt;&lt;tex-math notation="LaTeX"&gt;$\rho$&lt;/tex-math&gt;&lt;/inline-formula&gt;=0.20, respectively). Conclusion: Our findings underline the feasibility of generating composite maps by stitching spatially overlapping recordings. Significance: Composite maps can be instrumental in personalized ablation strategies.</p

Enthesitis on Chip - A Model for Studying Acute and Chronic Inflammation of the Enthesis and its Pharmacological Treatment

Enthesitis, the inflammation of the enthesis, which is the point of attachment of tendons and ligaments to bones, is a common musculoskeletal disease. The inflammation often originates from the fibrocartilage region of the enthesis as a consequence of mechanical overuse or -load and consequently tissue damage. During enthesitis, waves of inflammatory cytokines propagate in(to) the fibrocartilage, resulting in detrimental, heterotopic bone formation. Understanding of human enthesitis and its treatment options is limited, also because of lacking in vitro model systems that can closely mimic the pathophysiology of the enthesis and can be used to develop therapies. In this study, an enthes(it)is-on-chip model is developed. On opposite sides of a porous culture membrane separating the chip's two microfluidic compartments, human mesenchymal stromal cells are selectively differentiated into tenocytes and fibrochondrocytes. By introducing an inflammatory cytokine cocktail into the fibrochondrocyte compartment, key aspects of acute and chronic enthesitis, measured as increased expression of inflammatory markers, can be recapitulated. Upon inducing chronic inflammatory conditions, hydroxyapatite deposition, enhanced osteogenic marker expression and reduced secretion of tissue-related extracellular matrix components are observed. Adding the anti-inflammatory drug celecoxib to the fibrochondrocyte compartment mitigates the inflammatory state, demonstrating the potential of the enthesitis-on-chip model for drug testing

Transplantation of Predegenerated Peripheral Nerves after Complete Spinal Cord Transection in Rats:Effect of Neural Precursor Cells and Pharmacological Treatment with the Sulfoglycolipid Tol-51

Following spinal cord injury (SCI), the regenerative capacity of the central nervous system (CNS) is severely limited by the failure of axonal regeneration. The regeneration of CNS axons has been shown to occur by grafting predegenerated peripheral nerves (PPNs) and to be promoted by the transplantation of neural precursor cells (NPCs). The introduction of a combinatorial treatment of PPNs and NPCs after SCI has to address the additional problem of glial scar formation, which prevents regenerating axons from leaving the implant and making functional connections. Previously, we discovered that the synthetic sulfoglycolipid Tol-51 inhibits astrogliosis. The objective was to evaluate axonal regeneration and locomotor function improvement after SCI in rats treated with a combination of PPN, NPC, and Tol-51. One month after SCI, the scar tissue was removed and replaced with segments of PPN or PPN+Tol-51; PPN+NPC+Tol-51. The transplantation of a PPN segment favors regenerative axonal growth; in combination with Tol-51 and NPC, 30% of the labeled descending corticospinal axons were able to grow through the PPN and penetrate the caudal spinal cord. The animals treated with PPN showed significantly better motor function. Our data demonstrate that PPN implants plus NPC and Tol-51 allow successful axonal regeneration in the CNS

Prävalenz von chronischem Schmerz und funktionellen somatischen Syndromen in Deutschland:Systematisches Review und Metaanalyse

BackgroundChronic pain and functional somatic syndromes are associated with significant limitations in daily life. The national literature is inconsistent with respect to reports on the prevalence. ObjectiveAs part of a project on epidemiology in Europe, this study aims to more accurately determine the prevalence of chronic pain and functional somatic syndromes in the general adult population in Germany. Material and methodsA systematic literature search was conducted in the databases PubMed and Web of Science, followed by meta-analyses (https://osf.io/w52jm). Internationally published articles in the English language on the prevalence of chronic pain and functional somatic syndromes in the adult population were included. The quality of the studies was assessed using the appraisal checklist of the Joanna Briggs Institute. ResultsThe point prevalence estimates for chronic pain show a range from 14.3% to 22.6%. The overall point prevalence for chronic pain including 6 studies and 18,478 observations was 14.99% (95% confidence interval, CI 10.05-21.77%). The integration of prevalence estimates for functional somatic syndromes and somatoform disorders resulted in a pooled point prevalence rate of 7.35% (95% CI 4.54-11.70%) including 10 studies and 37,110 observations. The prevalence rates for both types of complaints were higher in females than in males. The Egger test showed no indication of publication bias. Subgroup analyses indicated a low risk of bias. ConclusionThe substantial heterogeneity of the prevalence rates underlines the need for a standardized diagnostic approach in research to ensure consistent and comparable data collection and analysis. The results are discussed against the background of the treatment situation in the German healthcare system and the urgency of developing efficient psychotherapeutic care models to meet the demand

Acute internal medicine physicians' clinical intuition based on acute care telephone referral:A prospective study

Introduction In the Netherlands, most emergency department (ED) patients are referred by a general practitioner (GP) or a hospital specialist. Early risk stratification during telephone referral could allow the physician to assess the severity of the patients' illness in the prehospital setting. We aim to assess the discriminatory value of the acute internal medicine (AIM) physicians' clinical intuition based on telephone referral of ED patients to predict short-term adverse outcomes, and to investigate on which information their predictions are based.Methods In this prospective study, we included adult ED patients who were referred for internal medicine by a GP or a hospital specialist. Primary outcomes were hospital admission and triage category according to the Manchester Triage System (MTS). Secondary outcome was 31-day mortality. The discriminatory performance of the clinical intuition was assessed using an area under the receiver operating characteristics curve (AUC). To identify which information is important to predict adverse outcomes, we performed univariate regression analysis. Agreement between predicted and observed MTS triage category was assessed using intraclass and Spearman's correlation.Results We included 333 patients, of whom 172 (51.7%) were referred by a GP, 146 (43.8%) by a hospital specialist, and 12 (3.6%) by another health professional. The AIM physician's clinical intuition showed good discriminatory performance regarding hospital admission (AUC 0.72, 95% CI: 0.66-0.78) and 31-day mortality (AUC 0.73, 95% CI: 0.64-0.81). Univariate regression analysis showed that age &gt;= 65 years and a sense of alarm were significant predictors. The predicted and observed triage category were similar in 45.2%, but in 92.5% the prediction did not deviate by more than one category. Intraclass and Spearman's correlation showed fair agreement between predicted and observed triage category (ICC 0.48, Spearman's 0.29).Conclusion Clinical intuition based on relevant information during a telephone referral can be used to accurately predict short-term outcomes, allowing for early risk stratification in the prehospital setting and managing ED patient flow more effectively

Beyond PDE4 inhibition:A comprehensive review on downstream cAMP signaling in the central nervous system

Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates signal transduction pathways pivotal for numerous biological functions. Intracellular cAMP levels are spatiotemporally regulated by their hydrolyzing enzymes called phosphodiesterases (PDEs). It has been shown that increased cAMP levels in the central nervous system (CNS) promote neuroplasticity, neurotransmission, neuronal survival, and myelination while suppressing neuroinflammation. Thus, elevating cAMP levels through PDE inhibition provides a therapeutic approach for multiple CNS disorders, including multiple sclerosis, stroke, spinal cord injury, amyotrophic lateral sclerosis, traumatic brain injury, and Alzheimer's disease. In particular, inhibition of the cAMP-specific PDE4 subfamily is widely studied because of its high expression in the CNS. So far, the clinical translation of full PDE4 inhibitors has been hampered because of dose-limiting side effects. Hence, focusing on signaling cascades downstream activated upon PDE4 inhibition presents a promising strategy, offering novel and pharmacologically safe targets for treating CNS disorders. Yet, the underlying downstream signaling pathways activated upon PDE(4) inhibition remain partially elusive. This review provides a comprehensive overview of the existing knowledge regarding downstream mediators of cAMP signaling induced by PDE4 inhibition or cAMP stimulators. Furthermore, we highlight existing gaps and future perspectives that may incentivize additional downstream research concerning PDE(4) inhibition, thereby providing novel therapeutic approaches for CNS disorders