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The recognition of constipation as a possible non‐Immunoglobulin E (IgE)‐mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE‐mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non‐IgE‐Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review. [ABSTRACT FROM AUTHOR]

Background & Aims: Progressive familial intrahepatic cholestasis (PFIC) relates to a group of rare, debilitating, liver disorders which typically present in early childhood, but have also been reported in adults. Without early detection and effective treatment, PFIC can result in end-stage liver disease. The aim of the paper was to put forward recommendations that promote standardisation of the management of PFIC in clinical practice. Methods: A committee of six specialists came together to discuss the challenges faced by physicians in the management of PFIC. The committee agreed on two key areas where expert guidance is required to optimise care: (1) how to diagnose and treat patients with a clinical presentation of PFIC in the absence of clear genetic test results/whilst awaiting results, and (2) how to monitor disease progression and response to treatment. A systematic literature review was undertaken to contextualise and inform the recommendations. Results: An algorithm was developed for the diagnosis and treatment of children with suspected PFIC. The algorithm recommends the use of licensed inhibitors of ileal bile acid transporters as the first-line treatment for patients with PFIC and suggests that genetic testing be used to confirm genotype whilst treatment is initiated in patients in whom PFIC is suspected. The authors recommend referring patients to an experienced centre, and ensuring that monitoring includes measurements of pruritus, serum bile acid levels, growth, and quality of life following diagnosis and during treatment. Conclusions: The algorithm presented within this paper offers guidance to optimise the management of paediatric PFIC. The authors hope that these recommendations will help to standardise the management of PFIC in the absence of clear clinical guidelines. Impact and implications: This opinion paper outlines a consistent approach to the contemporaneous diagnosis, monitoring, referral and management of children with progressive familial intrahepatic cholestasis. This should assist physicians given the recent developments in genetic diagnosis and the availability of effective drug therapy. This manuscript will also help to raise awareness of current developments and educate health planners on the place for new drug therapies in progressive familial intrahepatic cholestasis.

The anatomy of the human shoulder predisposes the neurovascular bundle to compression at different levels of the thoracic outlet during abduction of the arm. There are four possible levels of compression at the thoracic outlet pathway: at the costo-clavicular angle, the inter-scalenic angle, under the pectoralis minor muscle or at the level of the humeral head. The positional thoracic outlet compression (TOC) often remains completely asymptomatic. When symptomatic, compressions are collectively referred to as thoracic outlet syndrome (TOS) and may require surgery if physical therapy fails to improve symptoms. The “thoracic outlet compression with complications or sequelae” (the acronym of which is “TOC-CS”, which can be simplified as “TOX”) will almost invariably lead to surgery to release the compression, and other possible treatment targeting the complications as required. There is a continuum between TOC, TOS and TOX, which are simply different clinical stages of the same mechanical issue, just like the Rutherford grades represent different stages of lower extremity arterial disease. We believe that discriminating between TOC, TOS and TOX clarifies clinical definitions and their respective treatment options. TOC is to be considered as a physiological positional phenomenon, TOS requires medical or surgical treatment and surgery should be considered as a primary option in TOX.

Objectives: The primary objective was to evaluate the ECG trace paper evaluation current knowledge level in a group of Orthopaedic surgeons divided into juniors and seniors according to M.D. degree possession. Methods: A cross sectional study through self-administered questionnaires at a university hospital Orthopaedic and Trauma Surgery Department. The questionnaire included five sections: 1-Basic participants' characteristics, 2-Participants' perception of their ECG evaluation current knowledge level, 3-The main body of the questionnaire was an ECG quiz (seven); the participant was asked to determine if it was normal and the possible diagnosis, 4-Participants' desired ECG evaluation knowledge level, and 5-Willingness to attend ECG evaluation workshops. Results: Of the 121 actively working individuals in the department, 96 (97.3 %) finished the questionnaire, and 85 (77.3 %) were valid for final evaluation. The participants' mean age was 30.4 ± 6.92 years, 76.5 % juniors and 23.5 % seniors. 83.5 % of the participants perceived their current ECG evaluation knowledge as none or limited. For participants' ability to evaluate an ECG, higher scores were achieved when determining if the ECG was normal or abnormal, with a mean score percentage of 79.32 % ± 23.27. However, the scores were lower when trying to reach the diagnosis, with a mean score percentage of 43.02 % ± 27.48. There was a significant negative correlation between the participant's age and answering the normality question correctly (r = −0.277, p = 0.01); and a significant positive correlation between answering the diagnosis question correctly and the desired level of knowledge and the intention to attend a workshop about ECG evaluation, r = 0.355 (p = 0.001), and r = 0.223 (p = 0.04), respectively. Only 56.5 % of the participants desired to get more knowledge, and 81.2 % were interested in attending ECG evaluation workshops. Conclusion: Orthopaedic surgeons showed sufficient knowledge when determining the normality of ECG trace papers; however, they could not reach the proper diagnosis, and Junior surgeons performed slightly better than their senior peers. Most surgeons are willing to attend ECG evaluation and interpretation workshops to improve their knowledge level.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the clinical management of valvular heart diseases with reference to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee tried to reflect the recently published results on the topic of valvular heart diseases and Korean data by a systematic literature search based on validity and relevance. In part I of this article, we will review and discuss the current position of aortic valve disease in Korea. [ABSTRACT FROM AUTHOR]

Summary This Good Practice Paper provides recommendations for the diagnosis and initial management of transplant‐eligible high‐risk myeloma patients. It describes recent updates to the genetic diagnostics of high‐risk myeloma and provides recommendations for treatment on the basis of recent prospective clinical trial evidence. [ABSTRACT FROM AUTHOR]

BackgroundCongo Red Dot Paper Test (CRDPT) appears to be a simple, cost-effective, non-invasive diagnostic tool for hypertensive disorders of pregnancy (HDP). The main objective of the study is to assess the effectiveness of CRDPT in detecting HDP.MethodsThis is a systemic review and meta-analysis of published studies on the effectiveness of CRDPT in the detection of HDP. The study was conducted in line with the PRISMA-DTA guidelines. The PICOS framework was used to search for relevant articles using Medline, PubMed, Google Scholar, Web of Science, and the Cochrane Library databases. The articles were screened against a set of inclusion and exclusion criteria and analysed using the Review Manager 5.4 software.ResultsA title, abstract and full article screening was conducted on 18,153 potential articles based on the inclusion and exclusion criteria. The screening yielded five articles for meta-analysis. The total number of normotensive pregnant women (n = 3,380) in the included studies was five times higher than the total number of women with pre-eclampsia (n = 535). A difference between the HDP and normotensive group was noted. This is indicated by a significantly decreased in the effectiveness of CRDPT in detecting HDP as compared to normotensive group [Risk Ratio (RR) = 6.32 (2.17, 18.43) p

Endometriosis is a common yet under-recognised chronic inflammatory disease, affecting 176 million women, trans and gender diverse people globally. The National Endometriosis Clinical and Scientific Trials (NECST) Registry is a new clinical registry collecting and tracking diagnostic and treatment data and patient-reported outcomes on people with endometriosis. The registry is a research priority action item from the 2018 National Action Plan for Endometriosis and aims to provide large-scale, national and longitudinal population-based data on endometriosis. Working groups (consisting of patients with endometriosis, clinicians and researchers) developing the NECST Registry data dictionary and data collection platform started in 2019. Our data dictionary was developed based on existing and validated questionnaires, tools, meta-data and data cubes – World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project, endometriosis CORE outcomes set, patient-reported outcome measures, the International Statistical Classification of Diseases-10th Revision Australian Modification diagnosis codes and Australian Government datasets: Australian Institute for Health and Welfare (for sociodemographic data), Medicare Benefits Schedule (for medical procedures) and the Pharmaceutical Benefits Scheme (for medical therapies). The resulting NECST Registry is an online, secure cloud-based database, prospectively collecting minimum core clinical and health data across eight patient and clinician modules and longitudinal data tracking disease life course. The NECST Registry has ethics approval (HREC/62508/ MonH-2020) and is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000987763).

To improve the storage and transport of clinical specimens for the diagnosis of Neisseria meningitidis (Nm) infections in resource-limited settings, we have evaluated the performance of dried blood spot (DBS) and dried cerebrospinal fluid spot (DCS) assays. DBS and DCS were prepared on filter paper from liquid specimens previously tested for Nm in the United Kingdom. Nm was detected and genogrouped by real-time PCR performed on crude genomic DNA extracted from the DBS (n = 226) and DCS (n = 226) specimens. Targeted whole-genome sequencing was performed on a subset of specimens, DBS (n = 4) and DCS (n = 6). The overall agreement between the analysis of liquid and dried specimens was (94.2%; 95% CI 90.8–96.7) for blood and (96.4%; 95% CI 93.5–98.0) for cerebrospinal fluid. Relative to liquid specimens as the reference, the DBS and DCS assays had sensitivities of (89.1%; 95% CI 82.7–93.8) and (94.2%; 95% CI 88.9–97.5), respectively, and both assays had specificities above 98%. A genogroup was identified by dried specimen analysis for 81.9% of the confirmed meningococcal infections. Near full-length Nm genome sequences (>86%) were obtained for all ten specimens tested which allowed determination of the sequence type, clonal complex, presence of antimicrobial resistance and other meningococcal genotyping. Dried blood and CSF filter spot assays offer a practical alternative to liquid specimens for the molecular and genomic characterisation of invasive meningococcal diseases in low-resource settings. [ABSTRACT FROM AUTHOR]

• The EEG is one of the most useful technologies for brain research and clinical neurology. • The acquired traces are visibly displayed, but various studies investigate the translation of brain waves in sound. • The analog EEG was equipped with an auditory output, the pen-on-paper noise made by the writer unit, useful to facilitate the diagnosis of epileptic disorders. • Early digital EEG devices could be equipped with special software to duplicate the pen-on-paper noise digitally. • Nowadays, auditory neurofeedback has applications in therapeutic interventions, cognitive improvement, and basic research. The electroencephalogram (EEG) is one of the most useful technologies for brain research and clinical neurology, characterized by non-invasiveness and high time resolution. The acquired traces are visibly displayed, but various studies investigate the translation of brain waves in sound (i.e., a process called sonification). Several articles have been published since 1934 about the sonification of EEG traces, in the attempt to identify the "brain-sound." However, for a long time this sonification technique was not used for clinical purposes. The analog EEG was in fact already equipped with an auditory output, although rarely mentioned in scientific papers: the pen-on-paper noise made by the writer unit. EEG technologists often relied on the sound that pens made on paper to facilitate the diagnosis. This article provides a sample of analog video-EEG recordings with audio support representing the strengths of a combined visual-and-auditory detection of different types of seizures. The purpose of the present article is to illustrate how the analog EEG "sounded," as well as to highlight the advantages of this pen-writing noise. It was considered so useful that early digital EEG devices could be equipped with special software to duplicate it digitally. Even in the present days, the sonification can be considered as an attempt to modify the EEG practice using auditory neurofeedback with applications in therapeutic interventions, cognitive improvement, and basic research. [ABSTRACT FROM AUTHOR]

Paper-based electrochemical analytical devices (ePADs) have gained significant interest as promising analytical units in recent years because they can be fabricated in simple ways, are low-cost, portable, and disposable platforms that can be applied in various fields. In this sense, paper-based electrochemical biosensors are attractive analytical devices since they can promote diagnose several diseases and potentially allow decentralized analysis. Electrochemical biosensors are versatile, as the measured signal can be improved by using mainly molecular technologies and nanomaterials to attach biomolecules, resulting in an increase in their sensitivity and selectivity. Additionally, they can be implemented in microfluidic devices that drive and control the flow without external pumping and store reagents, and improve the mass transport of analytes, increasing sensor sensitivity. In this review, we focus on the recent developments in electrochemical paper-based devices for viruses' detection, including COVID-19, Dengue, Zika, Hepatitis, Ebola, AIDS, and Influenza, among others, which have caused impacts on people's health, especially in places with scarce resources. Also, we discuss the advantages and disadvantages of the main electrode's fabrication methods, device designs, and biomolecule immobilization strategies. Finally, the perspectives and challenges that need to be overcome to further advance paper-based electrochemical biosensors' applications are critically presented. [ABSTRACT FROM AUTHOR]

This article provides information on the diagnosis and management of smouldering myeloma, a precursor condition to multiple myeloma. It discusses various diagnostic tests and imaging techniques used to identify smouldering myeloma and emphasizes the importance of restaging if there is evidence of progression. The article also provides recommendations for screening and initial investigations for suspected myeloma. Additionally, it discusses risk stratification models and treatment options for smouldering myeloma, including the use of lenalidomide. The article concludes by highlighting ongoing clinical trials and the need for further research in the treatment of smouldering myeloma. [Extracted from the article]

This article summarizes several studies on various topics. The first study examines the relationship between internalizing symptoms and problematic pornography use in college students, finding that higher levels of internalizing symptoms are associated with higher levels of problematic pornography use. The second study focuses on sleep-wake disorders among veterans with opioid use disorder, revealing that 24.4% of veterans with opioid use disorder have a sleep disorder, with obstructive sleep apnea being the most common type. The third study explores the association between cannabis use and lifetime suicidal ideation and attempts, finding that cannabis use is associated with an increased risk of suicidal ideation and attempts. Another study examines the impact of mandatory buprenorphine training and the removal of the X-waiver on prescribing patterns for physicians, showing that while there was an increase in knowledge and a decrease in concern about legal consequences after training, there were no significant differences in buprenorphine prescribing patterns. The fifth study focuses on emergency department patients with illicit fentanyl use and co-occurring psychiatric disorders, highlighting the prevalence of illicit fentanyl use and the need for routine assessments and treatment for mental health and substance misuse in this population. Lastly, a study examines the burden of emergency admissions and hospitalizations for nonfatal acute iatrogenic events in people with sickle cell disease and opioid dependence or tolerance, emphasizing the need for improved interventions and better access to care for this population. The first article also highlights the need for further research to improve opioid treatment strategies and [Extracted from the article]

Excessive trabeculation, often referred to as "noncompacted" myocardium, has been described at all ages, from the fetus to the adult. Current evidence for myocardial development, however, does not support the formation of compact myocardium from noncompacted myocardium, nor the arrest of this process to result in so-called noncompaction. Excessive trabeculation is frequently observed by imaging studies in healthy individuals, as well as in association with pregnancy, athletic activity, and with cardiac diseases of inherited, acquired, developmental, or congenital origins. Adults with incidentally noted excessive trabeculation frequently require no further follow-up based on trabecular pattern alone. Patients with cardiomyopathy and excessive trabeculation are managed by cardiovascular symptoms rather than the trabecular pattern. To date, the prognostic role of excessive trabeculation in adults has not been shown to be independent of other myocardial disease. In neonates and children with excessive trabeculation and normal or abnormal function, clinical caution seems warranted because of the reported association with genetic and neuromuscular disorders. This report summarizes the evidence concerning the etiology, pathophysiology, and clinical relevance of excessive trabeculation. Gaps in current knowledge of the clinical relevance of excessive trabeculation are indicated, with priorities suggested for future research and improved diagnosis in adults and children. [Display omitted] • Current evidence shows that the extent of trabeculated vs compact myocardium in the adult is determined by differential (allometric) growth of each myocardial layer. Because trabeculated myocardium does not coalesce to form the compact myocardial wall, the term "left ventricular noncompaction" is inaccurate and use should be discouraged. • Excessive trabeculation, as diagnosed using existing criteria, may be present as a normal variant or as a response to preload conditions. • In adults incidentally found to have excessive trabeculation with normal myocardial function and morphology, clinical management is determined by other cardiovascular symptoms or abnormalities, without regard to trabecular pattern. • In adults diagnosed with hypertrophic or dilated cardiomyopathy where excessive trabeculation is also present, the extent of ventricular trabeculation has not been demonstrated to alter management nor prognosis. Following guidelines developed specifically for those conditions is recommended. • In infants and children, caution is warranted because fewer data are available regarding the etiology and prognosis of excessive trabeculation. Clinical evaluation for occult neuromuscular disease or another genetic/metabolic etiology may be appropriate. [ABSTRACT FROM AUTHOR]

Guidelines and recommendations for the diagnosis and management of cow’s milk allergy (CMA) in childhood are based on scientific review of the available evidence. While this approach is the most rigorous, guidelines may not fully address all scenarios encountered by clinicians. Many symptoms of CMA overlap with other common childhood illnesses and are subjectively reported by the caregivers of the infant, as is the interpretation of the dietary interventions. Additionally, many healthcare professionals and caregivers do not follow the recommendations to perform an oral food challenge or reintroduction of cow’s milk after a diagnostic elimination diet because (1) the infant is doing well and (2) the carer’s fear of symptoms relapsing with this procedure. As a result, CMA in infants may be either under-diagnosed leading to reduced quality of life for families or over-diagnosed, resulting in unnecessary long-term elimination diets and increasing the risk for nutritional deficiencies. This paper discusses some of these controversial topics, focusing on misdiagnosis and mismanagement in clinical practice. The lack of objective diagnostic criteria can hamper the diagnosis and management of CMA in daily practice.

Background and objectives: Microscopic agglutination test is the gold standard sero-diagnostic method for detection of leptospirosis. Moreover, it helps identify serovars and their titers in serum samples. For obtaining accurate titer results, proper sampling, collection, storage, and transportation of samples are crucial while maintaining the cold chain. Since storage for long periods and the subsequent deterioration of samples may affect the final titers, we proposed an alternative method of MAT testing using filter paper-dried serum samples. We also evaluated sensitivity and specificity of the MAT test by using filtered-dried serum samples compared with the conventional MAT test. Methods: This experimental study was performed on human and animal serum samples that were sent to a reference leprospirosis laboratory in 2020. Overall, 142 positive samples (with 289 titers for different strains) and 15 negative samples were used for MAT test using filtered-dried serum. For this purpose, each sample was dried on a filter paper (Whatman 903, GE Healthcare) at room temperature (20-30 °C) and kept for four days. On the fifth day, the filter papers were cut into small pieces, soaked in phosphate buffer saline, vortexed, and slowly mixed on shaker for two hours to elute antibodies. The MAT tests were performed simultaneously and under the same environmental conditions. Results: The new MAT test using dried serum samples showed 79% sensitivity and 100% specificity. The test also had positive predictive value of 92% and negative predictive value of 24% when compared with the gold standard MAT test. Conclusion: Filter-dried serum can be used for MAT test to overcome serum storage and transportation problems.

Paracetamol overdose is a leading cause of acute liver failure that can prove fatal. Establishing paracetamol concentration accurately and quickly is critical. Current detection methods are invasive, time-consuming and/or expensive. Non-invasive, rapid and cost-effective techniques are urgently required. To address this challenge, a novel approach, called Paper-Arrow Mass Spectrometry (PA-MS) has been developed. This technique combines sample collection, extraction, enrichment, separation and ionisation onto a single paper strip, and the entire analysis process, from sample to result, can be carried out in less than 10 min requiring only 2 μL of raw human saliva. PA-MS achieved a LOQ of 185 ng mL−1, mean recovery of 107 ± 7%, mean accuracy of 11 ± 8% and precision ≤5% using four concentrations, and had excellent linearity (r2 = 0.9988) in the range of 0.2–200 μg mL−1 covering the treatment concentration range, surpassing the best-in-class methods currently available for paracetamol analysis. Furthermore, from a panel of human saliva samples, inter-individual variability was found to be <10% using this approach. This technique represents a promising tool for rapid and accurate emergency diagnosis. [ABSTRACT FROM AUTHOR]

In human history, the paper has long been used as a platform to record and preserve information. However, over the decades, paper has found its application in Biomedical Sciences, too. Both paper-based microfluidic devices (μPADs) and paper-based cultures and scaffolds have shown immense potential to be used as a sensor as well as a supporting material for in vitro tissue engineering. μPADs can be used to perform low-cost and fast biomolecular assays at Point-Of-Care (POC). They are being used to detect various biomarkers like viral proteins, metabolites, oncogenes, and antigens; and conditions like Venous Thromboembolism (VTE). On the other hand, the paper has also been used to develop paper-based 3D cultures and scaffolds to test drugs, and monitor cytotoxic effects in vitro cell microenvironments and also as implantable tissues. In this review, we intend to enumerate the development in the field of μPADs, paper-based cell cultures, and paper-based scaffolds and their plethora of applications over the last decade.

Delirium is a common complication in acute stroke patients, occurring in 15–35% of all stroke unit admissions and is associated with prolonged hospital stay and a poor post-stroke prognosis. Managing delirium in acute stroke patients necessitates an intensive and multiprofessional therapeutic approach, placing a significant burden on healthcare staff. However, dedicated practical recommendations for delirium management developed for the population of acute stroke patients are lacking. For this purpose, the Austrian Stroke Society, in cooperation with the Austrian Society of Neurology, the Austrian Society of Neurorehabilitation, and the Austrian Society of Psychiatry, Psychotherapy, and Psychosomatics has formulated an evidence-based position paper addressing the management of delirium in acute stroke patients. The paper outlines practical recommendations on the three pillars of care in stroke patients with delirium: (a) Key aspects of delirium prevention including stroke-specific delirium risk factors and delirium prediction scores are described. Moreover, a non-pharmacological delirium prevention bundle is presented. (b) The paper provides recommendations on timing and frequency of delirium screening to ensure early diagnosis of delirium in acute stroke patients. Moreover, it reports on the use of different delirium screening tools in stroke populations. (c) An overview of non-pharmacological and pharmacological treatment strategies in patients with delirium and acute stroke is presented and summarized as key recommendation statements. [ABSTRACT FROM AUTHOR]

ImportanceThe post-thrombotic syndrome (PTS) is the most common long-term complication of deep vein thrombosis (DVT), occurring in up to 40–50% of cases. There are limited evidence-based approaches for PTS clinical management.ObjectiveTo provide an expert consensus for PTS diagnosis, prevention, and treatment.Evidence-ReviewMEDLINE, Cochrane Database review, and GOOGLE SCHOLAR were searched with the terms “post-thrombotic syndrome” and “post-phlebitic syndrome” used in titles and abstracts up to September 2020.Filters WereEnglish, Controlled Clinical Trial / Systematic Review / Meta-Analysis / Guideline. The relevant literature regarding PTS diagnosis, prevention and treatment was reviewed and summarized by the evidence synthesis team. On the basis of this review, a panel of 15 practicing angiology/vascular medicine specialists assessed the appropriateness of several items regarding PTS management on a Likert-9 point scale, according to the RAND/UCLA method, with a two-round modified Delphi method.FindingsThe panelists rated the following as appropriate for diagnosis: 1-the Villalta scale; 2- pre-existing venous insufficiency evaluation; 3-assessment 3–6 months after diagnosis of iliofemoral or femoro-popliteal DVT, and afterwards periodically, according to a personalized schedule depending on the presence or absence of clinically relevant PTS. The items rated as appropriate for symptom relief and prevention were: 1- graduated compression stockings (GCS) or elastic bandages for symptomatic relief in acute DVT, either iliofemoral, popliteal or calf; 2-thigh-length GCS (30–40 mmHg at the ankle) after ilio-femoral DVT; 3- knee-length GCS (30–40 mmHg at the ankle) after popliteal DVT; 4-GCS for different length of times according to the severity of periodically assessed PTS; 5-catheter-directed thrombolysis, with or without mechanical thrombectomy, in patients with iliofemoral obstruction, severe symptoms, and low risk of bleeding. The items rated as appropriate for treatment were: 1- thigh-length GCS (30–40 mmHg at the ankle) after iliofemoral DVT; 2-compression therapy for ulcer treatment; 3- exercise training. The role of endovascular treatment (angioplasty and/or stenting) was rated as uncertain, but it could be considered for severe PTS only in case of stenosis or occlusion above the inguinal ligament, followed by oral anticoagulation.Conclusions and RelevanceThis position paper can help practicing clinicians in PTS management.

Background Cutaneous leishmaniasis (CL) is generally diagnosed by molecular methods, including PCR, using biopsy samples, skin scrapings and clinical exudates. In this study, we assessed the PCR performance for diagnosis of CL using skin of biopsy samples vs PCR of skin lesion exudate samples on filter paper and compared the diagnostic concordance of PCR using both sampling methods. Methods We assessed the PCR performance using 80 skin biopsy samples and 80 filter paper samples containing exudates from skin lesions obtained from 74 patients with clinical suspicion of CL in Cusco, Peru. Results : PCR using skin biopsy samples had superior diagnostic accuracy compared with filter paper PCR (62.5% [50/80] vs 38.7% [31/80], respectively; p˂0.005) and the diagnostic concordance between both sampling methods was 'moderate' (kappa coefficient=0.50, 95% CI 0.98 to 1.0). Conclusions PCR using biopsy samples remains the standard for diagnosis of CL. [ABSTRACT FROM AUTHOR]

Background and objectives: Microscopic agglutination test is the gold standard sero-diagnostic method for detection of leptospirosis. Moreover, it helps identify serovars and their titers in serum samples. For obtaining accurate titer results, proper sampling, collection, storage, and transportation of samples are crucial while maintaining the cold chain. Since storage for long periods and the subsequent deterioration of samples may affect the final titers, we proposed an alternative method of MAT testing using filter paper-dried serum samples. We also evaluated sensitivity and specificity of the MAT test by using filtered-dried serum samples compared with the conventional MAT test. Methods: This experimental study was performed on human and animal serum samples that were sent to a reference leprospirosis laboratory in 2020. Overall, 142 positive samples (with 289 titers for different strains) and 15 negative samples were used for MAT test using filtered-dried serum. For this purpose, each sample was dried on a filter paper (Whatman 903, GE Healthcare) at room temperature (20-30 °C) and kept for four days. On the fifth day, the filter papers were cut into small pieces, soaked in phosphate buffer saline, vortexed, and slowly mixed on shaker for two hours to elute antibodies. The MAT tests were performed simultaneously and under the same environmental conditions. Results: The new MAT test using dried serum samples showed 79% sensitivity and 100% specificity. The test also had positive predictive value of 92% and negative predictive value of 24% when compared with the gold standard MAT test. Conclusion: Filter-dried serum can be used for MAT test to overcome serum storage and transportation problems. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis remains a serious public health issue, and Brazil was among the seven countries with the highest prevalence of this disease worldwide. The measures to control this disease are not easily developed, and the improvement of its diagnosis, surveillance, and control is still needed. This study aimed to carry out the polymerase chain reaction (PCR) diagnosis of Leishmania infantum in vector samples in some municipalities of the State of São Paulo, which included two municipalities with human disease transmission and two with dog transmission only. Vectors were collected in traps with luminous bait. Next, they were killed at −4 °C and kept in 70% alcohol. Groups of ten female insects (pools) were mashed on cation exchange paper (fine cellulose phosphate with 18 µEq/cm² ionic exchange capacity) for DNA extraction. The PCR was carried out to identify the natural infection of the Leishmania genus in female Lutzomyia longipalpis (Lu. Longipalpis). Out of the 3,880 Lu. longipalpis phlebotomines, 1060 were female and 2820 were male (3:1). The method used to extract the DNA in pools of ten phlebotomines and the PCR resulted in sensitivity, specificity, practicality, and faster analyses when compared to the individual analysis method. The procedure described can be used on a large scale in the leishmaniasis epidemiological surveillance, enabling a higher number of analyses and the optimization of human resources because the traditional diagnostic method is carried out via desiccation of the insect digestive system and microscopic examination, which is time-demanding and there is the need of manual skills.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life. [ABSTRACT FROM AUTHOR]

This ENETS guidance paper, developed by a multidisciplinary working group, provides up‐to‐date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11–12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first‐line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second‐line treatment. Immunotherapy plays a minor role in biomarker‐unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease. [ABSTRACT FROM AUTHOR]

Molecularly imprinted polymers are efficient and selective adsorbents which act as artificial receptors for desired compounds with the ability to recognize the size, shape, and functional groups of the compounds simultaneously. A molecularly imprinted polymer is prepared by the polymerization of functional monomers around a template (analyte) molecule. Afterward, the removal of the template from the polymer matrix leaves a selective cavity behind. The fabrication and development of molecularly imprinted polymers grew rapidly, due to their low cost, simple preparation, selectivity, sensitivity, and stable physicochemical properties. Traditionally, molecularly imprinted polymers can be synthesized using two main methods, namely bulk and surface imprinting. For more efficient use of the latter method, researchers have developed molecularly imprinted polymers grafted on the solid-phase matrix (substrate). This grafting technique would be particularly useful for surface imprinting of macromolecules, such as proteins. Cellulose fibers of papers with unique properties such as being abundant, retaining a porous structure, having good adsorption properties, and possessing hydroxyl groups naturally have gained much attention as substrate. The goal of this review is to introduce molecularly imprinted polymer-grafted or molecularly imprinted polymer-coated paper, as an interesting, simple, and efficient method in the detection and separation of small and large molecules. Therefore, in the present paper, several recent preparation techniques and applications of molecularly imprinted polymer-grafted paper are reviewed and discussed in detail. [ABSTRACT FROM AUTHOR]

In vitro diagnosis (IVD) has become a hot topic in laboratory research and achievement transformation. However, due to the high cost, and time-consuming and complex operation of traditional technologies, some new technologies are being introduced into IVD, to solve the existing problems. As a result, IVD has begun to develop toward point-of-care testing (POCT), a subdivision field of IVD. The pandemic has made governments and health institutions realize the urgency of accelerating the development of POCT. Microfluidic paper-based analytical devices (μPADs), a low-cost, high-efficiency, and easy-to-operate detection platform, have played a significant role in advancing the development of IVD. μPADs are composed of paper as the core material, certain unique substances as reagents for processing the paper, and sensing devices, as auxiliary equipment. The published reviews on the same topic lack a comprehensive and systematic introduction to μPAD classification and research progress in IVD segmentation. In this paper, we first briefly introduce the origin of μPADs and their role in promoting IVD, in the introduction section. Then, processing and detection methods for μPADs are summarized, and the innovative achievements of μPADs in IVD are reviewed. Finally, we discuss and prospect the upgrade and improvement directions of μPADs, in terms of portability, sensitivity, and automation, to help researchers clarify the progress and overcome the difficulties in subsequent μPAD research. [ABSTRACT FROM AUTHOR]

Exercise-induced respiratory symptoms describe acute airway narrowing that occurs as a result of exercise. It includes exercise-induced bronchoconstriction (EIB) and exercise-induced asthma (EIA) issues. To provide clinicians with practical guidelines, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB/EIA and to develop evidence-based guidelines for the diagnosis and treatment. Recommendations for the diagnosis and treatment of EIB were developed. High-intensity exercise in polluted environment (cold air, humidity, contamination, allergens) may increase the risk of EIB and asthma symptoms in athletes. Diagnostic procedures should include history taking, physical examination, atopy assessment and functional tests of the respiratory system. A strong recommendation was made for regular use of inhaled glucocorticosteroids and avoidance of short-acting 2-agonists as the only treatment. The treatment of asthma in athletes should always take into account current anti-doping regulations. This position paper reflects the currently available evidence.

Abstract Drug hypersensitivity reactions (DHRs) in childhood are mainly caused by betalactam or non-betalactam antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs). Laboratory tests for identifying children who are allergic to drugs have low diagnostic accuracy and predictive value. The gold standard to diagnose DHR is represented by the drug provocation test (DPT), that aims of ascertaining the causative role of an allergen and evaluating the tolerance to the suspected drug. Different protocols through the administration of divided increasing doses have been postulated according to the type of drug and the onset of the reaction (immediate or non immediate reactions). DPT protocols differ in doses and time interval between doses. In this position paper, the Italian Pediatric Society for Allergy and Immunology provides a practical guide for provocation test to antibiotics and NSAIDs in children and adolescents.

Abstract INTRODUCTION: The objective of this study was to evaluate the performance of filter paper (FP) for lesion scraping collection in a polymerase chain reaction (PCR) for cutaneous leishmaniasis (CL) diagnosis. METHODS: Lesion scrapings from 48 patients were collected and analyzed for PCR. RESULTS: PCR with FP detected up to three Leishmania braziliensis promastigotes. Considering the direct search by microscopy or PCR of samples collected in STE buffer as standards, the sensitivity of PCR with FP was 100%. CONCLUSIONS: FP can be useful for CL diagnosis in remote regions, allowing high sensitivity in the detection of the parasite by PCR.

Aims: The epidemiologic Study of Women's Health Across the Nation (SWAN) includes urinary incontinence (UI) questionnaire items. We introduced an independently self‐administered paper towel test (PTT‐ISA; invention disclosure #2021‐347) to objectively demonstrate UI. Aims were to determine: (1) PTT‐ISA compliance and (2) relationship to questionnaire results. Methods: 276 community women were invited to complete both SWAN questionnaire and PTT‐ISA. For PTT‐ISA, a woman holds a trifold brown paper towel against her perineum while coughing hard three times. She checks the towel for wetness and compares it with pictorial showing wetted area gradations (dry towel through >6 ml/saturated). She then selects the best photo match for her towel. A newly conceptualized variable constructed as PTT‐ISA plus questionnaire results was formed. Results: Of 276 women, noncompliance with PTT‐ISA was 2.2% (6 women). Four others (1.5%) were missing questionnaires. For the remaining 266 women, conceptual cohesiveness between questionnaire‐only and PTT‐ISA + questionnaire was demonstrated in 165 (62.0%). Lack of cohesiveness occurred in 101 (38.9%), including 41 women who said "no" to the questionnaire item indicative of stress UI and had leakage on PTT‐ISA; leakage degree varied across the full pictorial spectrum from drops to saturated. Conclusion: PTT‐ISA demonstrates high compliance, with rate comparable to survey compliance. It is a novel measure for objective sign of urine loss when independently self‐administered by community women outside of a clinic environment. Further research comparing PTT‐ISA with clinician‐observed cough test is warranted. As independently self‐administered, PTT‐ISA is simple, noninvasive, inexpensive, and an acceptable test that adds value to otherwise survey‐dependent research. [ABSTRACT FROM AUTHOR]

This study describes a novel fabrication method of a multi-pad paper plate (MP 3 ) for transfer and optimisation of enzyme-linked immunosorbent assays (ELISA) on paper. The plate was fabricated using a combination of laser cutting and lamination for rapid and low-cost production of a multi-pad paper plate compatible with a standard 96 well microplate format. The plate was used to transfer a sandwich ELISA assay for detection of the acute phase protein bovine haptoglobin, allowing assay optimisation in the new format. The optimised protocol was also applied to detection of haptoglobin in bovine serum, demonstrating significant correlation with the traditional lab-based ELISA. [ABSTRACT FROM AUTHOR]

Gastro‐oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA‐associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA‐associated GORD and medical and dietary management. The task force (TF) on non‐IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web‐based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA‐associated GORD. [ABSTRACT FROM AUTHOR]

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Visceral leishmaniasis remains a serious public health issue, and Brazil was among the seven countries with the highest prevalence of this disease worldwide. The measures to control this disease are not easily developed, and the improvement of its diagnosis, surveillance, and control is still needed. This study aimed to carry out the polymerase chain reaction (PCR) diagnosis of Leishmania infantum in vector samples in some municipalities of the State of São Paulo, which included two municipalities with human disease transmission and two with dog transmission only. Vectors were collected in traps with luminous bait. Next, they were killed at −4 °C and kept in 70% alcohol. Groups of ten female insects (pools) were mashed on cation exchange paper (fine cellulose phosphate with 18 µEq/cm² ionic exchange capacity) for DNA extraction. The PCR was carried out to identify the natural infection of the Leishmania genus in female Lutzomyia longipalpis (Lu. Longipalpis). Out of the 3,880 Lu. longipalpis phlebotomines, 1060 were female and 2820 were male (3:1). The method used to extract the DNA in pools of ten phlebotomines and the PCR resulted in sensitivity, specificity, practicality, and faster analyses when compared to the individual analysis method. The procedure described can be used on a large scale in the leishmaniasis epidemiological surveillance, enabling a higher number of analyses and the optimization of human resources because the traditional diagnostic method is carried out via desiccation of the insect digestive system and microscopic examination, which is time-demanding and there is the need of manual skills. [ABSTRACT FROM AUTHOR]

Allergy and respiratory disorders are common in young athletic individuals. In the context of elite sport, it is essential to secure an accurate diagnosis in order to optimize health and performance. It is also important, however, to consider the potential impact or consequences of these disorders, in recreationally active individuals engaging in structured exercise and/or physical activity to maintain health and well‐being across the lifespan. This EAACI Task Force was therefore established, to develop an up‐to‐date, research‐informed position paper, detailing the optimal approach to the diagnosis and management of common exercise‐related allergic and respiratory conditions. The recommendations are informed by a multidisciplinary panel of experts including allergists, pulmonologists, physiologists and sports physicians. The report is structured as a concise, practically focussed document, incorporating diagnostic and treatment algorithms, to provide a source of reference to aid clinical decision‐making. Throughout, we signpost relevant learning resources to consolidate knowledge and understanding and conclude by highlighting future research priorities and unmet needs. [ABSTRACT FROM AUTHOR]

AbstractBackground.Establishing a valid communication is not only a basic clinical need to be met but also a relevant ethical commitment.Methods.On the basis of the relevant literature, ethical issues arising from specific, important situations in clinical practice were identified.Results.The main ethical problems regarding communication about the disorder, both in general and in relation to prodromal stages, were described and discussed together with those regarding communication about voluntary and involuntary treatments, “dual roles” enacted in clinical practice, genetic counseling, and end-of-life conditions; on the basis of what emerged, ethically driven indications and suggestions were provided.Conclusions.Several situations put the psychiatrist in front of relevant dilemmas and doubts which are no easy to face with; an ethically driven approach based upon the principle of the best interest of patients may support clinicians in their decisions.

Background and Purpose: Multiple sclerosis (MS) is an unpredictable disease characterised by a highly variable disease onset and clinical course. Three main clinical phenotypes have been described. However, distinguishing between the two progressive forms of MS can be challenging for clinicians. This article examines how the diagnostic definitions of progressive MS impact clinical research, the design of clinical trials and, ultimately, treatment decisions. Methods: We carried out an extensive review of the literature highlighting differences in the definition of progressive forms of MS, and the importance of assessing the extent of the ongoing inflammatory component in MS when making treatment decisions. Results: Inconsistent results in phase III clinical studies of treatments for progressive MS, may be attributable to differences in patient characteristics (e.g., age, clinical and radiological activity at baseline) and endpoint definitions. In both primary and secondary progressive MS, patients who are younger and have more active disease will derive the greatest benefit from the available treatments. Conclusions: We recommend making treatment decisions based on the individual patient's pattern of disease progression, as well as functional, clinical and imaging parameters, rather than on their clinical phenotype. Because the definition of progressive MS differs across clinical studies, careful selection of eligibility criteria and study endpoints is needed for future studies in patients with progressive MS. [ABSTRACT FROM AUTHOR]