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This ENETS guidance paper for well‐differentiated nonfunctioning pancreatic neuroendocrine tumours (NF‐Pan‐NET) has been developed by a multidisciplinary working group, and provides up‐to‐date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF‐Pan‐NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF‐Pan‐NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms. This ENETS guidance paper provides up‐to‐date practical advice on the NF‐Pan‐NET diagnosis and treatment. Management of NF‐Pan‐NET patients requires a NET‐dedicated MDT decision. ENETS Centres of Excellence should be strongly considered to be involved in the diagnostic‐therapeutic strategy of these patients. Further studies are needed to fulfil the unmet needs in this field focusing on prognostic molecular markers, dilemmas concerning the selection of a therapeutic approach as well as the sequence of their use to achieve success in the management of NF‐Pan‐NETs patients. [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]

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug‐induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work‐up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment. [ABSTRACT FROM AUTHOR]

In order to use 3D imaging technology in medical treatment, some strict rules must be followed. This is consistent with the previous article [1] that five conditions must be followed to obtain ideal three‐dimensional (3D) imaging. This paper continues to provide some important supplements. It is importent especially in remote 3D telemedicine. The condition of "simultaneous arrival" should be added to the second condition to make it more accurate. Otherwise, the imagery will cause dizziness, and cannot even form a stereo image. Especially in VR and AR, the head sometimes needs to rotate left and right. We cooperated with Ms. Liu, the chief stomatologist of Yayi Hospital (the co‐author of this paper), and based on the theory of non‐paraxial optics, we designed some additional instruments, such as bilateral screen stereo imager and stereo glasses, that were applied to stomatology, and achieved some preliminary results. For example, the plane image of skull that can be rotated 360 degrees by CT scan can be converted into stereoscopic images of various angles. The three dimensional distribution of root canal and artificial fixation post can be seen by moving X‐ray light to take two X‐ray photos of gingiva and then viewing with stereoscopic glasses. The stereo "image pair" of the upper jaw or lower jaw in the reflector can be photographed with a self‐madestereo camera by two side‐by‐side mobile phones. The stereo image of the oral cavity can be seen by the self‐designed stereo Imager or stereo glasses. This is just the beginning and this device can be extended into use in other medical subjects. Our 3D imaging technology has a promising future in the medical field due to the following qualities: its definition can reach to 5K ~ 8K, the color saturation and gray scale are never reduced, as well as the high magnification and brightness. [ABSTRACT FROM AUTHOR]

To examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers.We searched Ovid EMBASE for publications indexed by the category′therapeutic agents′, and the subcategory′adverse effects′, by country for 43 countries.We counted 1 810 202 papers world-wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies.Many local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts. [ABSTRACT FROM AUTHOR]

Abstract: UV‐based (PUVA and narrowband UVB) phototherapy is broadly and commonly used in the treatment of Cutaneous T‐cell Lymphomas (CTCL), yet unfortunately, the evidence for the efficacy of these treatments is based only on case series or prospective but non‐randomized studies. Therefore, no internationally approved guidelines exist and no standardization of schedules has been proposed. Recently, consensus guidelines have been published by the United States Cutaneous Lymphoma Consortium. The aim of this study was to review the biological and clinical evidences on PUVA and NB‐UVB in CTCL and to critically evaluate acceptability and feasibility of these guidelines in the real‐life setting from the perspective of the Cutaneous Lymphoma Task Force of the Italian Lymphoma Foundation (Fondazione Italiana Linfomi, FIL). [ABSTRACT FROM AUTHOR]

The American College of Clinical Pharmacy ( ACCP) published an initial white paper on herbal products in 2000. Since then, the global market for natural products has continued to expand, with tens of millions of consumers using such products on an annual basis in the United States alone. However, despite this expansion, natural products remain largely unregulated compared with prescription medications, have moderate- to low-level clinical evidence for efficacy, and continue to have safety concerns, including adulteration and misbranding. As comprehensive medication management experts, clinical pharmacists are uniquely qualified to navigate these concerns and advise patients appropriately. To develop and recommend a suitable care plan involving natural products, clinical pharmacists must establish a strong pharmacist-patient relationship, assess the appropriateness of therapy, educate the patient regarding key issues, and continuously monitor and follow up on the effectiveness of the care plan. This process should not only occur in an individual community or hospital setting, but also whenever a patient transitions from one care setting to another in cooperation with other clinicians. [ABSTRACT FROM AUTHOR]

The Vitiligo Global Issues Consensus Conference ( VGICC), through an international e-Delphi consensus, concluded that 'repigmentation' and 'maintenance of gained repigmentation' are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e-surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus. [ABSTRACT FROM AUTHOR]

Background Chronic heart failure ( HF) is a relevant and growing public health problem. Although the prognosis has recently improved, it remains a lethal disease, with a mortality that equals or exceeds that of many malignancies. Furthermore, chronic HF is costly, representing a large and growing drain on healthcare resources. Methods This narrative review is based on the material searched for and obtained via PubMed up to May 2017. The search terms we used were as follows: 'heart failure, echocardiography, natriuretic peptides' in combination with 'treatment, biomarkers, guidelines.' Results Recent studies have supported the value of natriuretic peptides ( NPs) and Doppler echocardiographic biomarkers of increased left ventricular ( LV) filling pressures or pulmonary congestion as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of pulsed-wave tissue and blood flow Doppler with NPs appears valuable in guiding HF management in the outpatient setting. In as much as both the echo and the plasma levels of NPs may reflect the presence of fluid overload and elevations of LV filling pressures, integrating NP and echocardiographic biomarkers with clinical findings may help the cardiologist to identify high-risk patients, that is to recognize whether a patient is stable or the condition is likely to evolve into decompensated HF, to optimize treatment, to improve the prognosis and to reduce rehospitalization. Conclusion We discussed the rationale and the clinical significance of combining follow-up echo and NP assessment to guide management of ambulatory patients with chronic HF. [ABSTRACT FROM AUTHOR]

Background Skin diseases constitute up to 40% of all notified occupational diseases in most European countries, predominantly comprising contact dermatitis, contact urticaria, and skin cancer. While insufficient prevention of work-related skin diseases (WRSD) is a top-priority problem in Europe, common standards for prevention of these conditions are lacking. Objective To develop common European standards on prevention and management of WRSD and occupational skin diseases (OSD). Method Consensus amongst experts within occupational dermatology was achieved with regard to the definition of minimum evidence-based standards on prevention and management of WRSD/OSD. Results By definition, WRSDs/OSDs are (partially or fully) caused by occupational exposure. The definition of OSD sensu stricto additionally includes diverging national legal requirements, with an impact on registration, prevention, management, and compensation. With the implementation of the classification of WRSD/OSD in the International Classification of Diseases (ICD) 11th Revision in future, a valid surveillance and comparability across countries will be possible. Currently, WRDS and OSD are still under-reported. Depending on legislation and regulations, huge differences exist in notification procedures in Europe, although notification is crucial to prevent chronic and relapsing disease. Facilities for early diagnosis, essential for individual patient management, should be based on existing guidelines and include a multidisciplinary approach. Patch testing is essential if contact dermatitis persists or relapses. Workplace exposure assessment of WRSD/OSD requires full labelling of product ingredients on material safety data sheets helping to identify allergens, irritants and skin carcinogens. Comparable standards in primary, secondary and tertiary prevention must be established in Europe to reduce the burden of WRSD/OSD in Europe. Conclusion The adoption of common European standards on prevention of WRSD/OSD will contribute to reduce the incidence of OSD and their socio-economic burden. [ABSTRACT FROM AUTHOR]

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals are at increased risk of developing haemolysis following treatment with various antimalarial drugs. Reliable field tests for G6PD deficiency are thus needed in chemotherapy studies and their validity has to be assessed. In two phase II clinical trials on methylene blue (MB) antimalarial therapy in rural Burkina Faso, paediatric and adult participants were tested for G6PD deficiency. The results of a haemoglobin-adjusted nicotinamide adenine dinucleotide phosphate (NADPH) fluorescence test on paper (NFP test) were compared with polymerase chain reaction (PCR)-based G6PD genotyping also using blood samples on filter papers. This is the first study comparing sensitivity and specificity of the two methods. There was good agreement between the NFP test results and the PCR findings. The estimate of the sensitivity of the NFP test was 98·2% (95·8–99·6%) and the specificity was 97·1% (94·2–99·2%). In conclusion, the NFP assay is a reliable and inexpensive method for large-scale G6PD deficiency screening in rural West Africa. [ABSTRACT FROM AUTHOR]

Cannabis-based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis-based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and nonspecialist prescribers on appropriate use of cannabis-based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis-based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline-recommended first- and second-line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer, non-neuropathic noncancer pain), the use of cannabis-based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis-based medicines should be terminated.Significance: This position paper provides expert recommendations for nonspecialist and specialist healthcare professionals in Europe, on the importance and the appropriate use of cannabis-based medicines as part of a multidisciplinary approach to pain management, in properly selected and supervised patients. [ABSTRACT FROM AUTHOR]

Fluorescence‐guided surgery (FGS) and other interventions are rapidly evolving as a class of technologically driven interventional approaches in which many surgical specialties visualize fluorescent molecular tracers or biomarkers through associated cameras or oculars to guide clinical decisions on pathological lesion detection and excision/ablation. The technology has been commercialized for some specific applications, but also presents technical challenges unique to optical imaging that could confound the utility of some interventional procedures where real‐time decisions must be made. Accordingly, the AAPM has initiated the publication of this Blue Paper of The Emerging Technology Working Group (TETAWG) and the creation of a Task Group from the Therapy Physics Committee within the Treatment Delivery Subcommittee. In describing the relevant issues, this document outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS technology and its applications. The presentation is not intended to be conclusive, but rather to inform the field of medical physics and stimulate the discussions needed in the field with respect to a seemingly low‐risk imaging technology that has high potential for significant therapeutic impact. This AAPM Task Group is working toward consensus around guidelines and standards for advancing the field safely and effectively. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is a major risk factor for development of coronary heart disease. Proper diagnosis and adequate treatment are vital to reducing morbidity and mortality associated with elevated serum lipid levels. The amount of literature in this area is overwhelming. To aid practitioners and educators in organizing this large body of information, we compiled key articles, guidelines, and consensus papers relative to the treatment of dyslipidemias. Research articles were chosen based on the significance of findings, relevance to practice, quality of research, and timeliness; recent articles were given priority over earlier ones unless they demonstrated groundbreaking findings. [ABSTRACT FROM AUTHOR]

The article presents information on Rhinosinusitis. Rhinosinusitis is a significant health problem which seems to mirror the increasing frequency of allergic rhinitis and which results in a large financial burden on society. The last decade has seen the development of a number of guidelines, consensus documents and position papers on the epidemiology, diagnosis and treatment of rhinosinusitis and nasal polyposis. The diagnosis of rhinosinusitis is made by a wide variety of practitioners, including allergologists, otolaryngologists, pulmonologists, primary care physicians and many others.

Based on the principle of non‐paraxial optics and through accurate calculation, an eccentric lens is designed which is specially used for viewing the stereoscopic image with two vertical screens composed of two mobile phones. If it is made into glasses, called them "stereoscopic glasses for mobile phone". If the display screen and stereoscopic glasses are packaged together, it is called "stereoscopic viewer with double vertical screens", It corresponds to the previous " stereoscopic viewer with double side horizontal screen o The former mainly watches stereoscopic images taken vertically, such as personal stereoscopic photo, remote stereoscopic medical treatment, precious cultural relics collection, etc., while the latter matches the 16:9 standard film and television taken horizontally. Mobile phone stereoscopic glasses can not only watch two vertical screen stereoscopic programs, but also watch left and right side‐by‐side programs on the screen of one mobile phone. It is easy to carry and has good imaging quality with no dizziness. It comes with 4G and 5G system, and the price of 3D viewing device is low. Therefore it is expected to become the standard configuration of mobile phones. [ABSTRACT FROM AUTHOR]

Aims Assessment of the impact of health research is a growing but problematic field. We examined how a combination of approaches might together inform assessment of the impact of a body of diabetes research published in 1981 and help identify factors behind success. Methods Three broad approaches were applied to the work of one team leader of acknowledged influence. Standard bibliographic analysis was complemented by a second approach which categorized the importance of the primary publications to the papers citing them, in four domains. In parallel, a third approach involved qualitative assessment using surveys, critical pathway analysis by, and interviews of, co-authors and external experts. Extending the approach incorporated key additional publications from other years. Results In 1981, the team leader published 29 papers. Citations to these 29 first generation papers varied from 1 to 76 and resulted in 799 second generation papers. Citations to these produced 12 891 third generation papers. Analysis of second generation papers suggested the cited first generation paper was thought to be of considerable or essential significance in only 9% of cases. While much research made little impact, qualitative analysis included a wealth of information, sometimes missed by standard bibliographic techniques, on where the identified research influenced important streams of clinical development. Analysis covered major research studies (such as the Diabetes Control and Complications Trial), insulin pump therapy, and career development of co-authors. Conclusions Understanding the impact of research requires multiple approaches. With refinement, these techniques could be employed more widely and potentially could inform research policy. [ABSTRACT FROM AUTHOR]

Background: The novel proteasome inhibitor carfilzomib alone or in combination with other agents is already one of the standard therapies for relapsed and/or refractory multiple myeloma (MM) patients and produces impressive response rates in newly diagnosed MM as well. However, carfilzomib-related cardiovascular adverse events (CVAEs) - including hypertension (all grades: 12.2%; grade ≥3: 4.3%), heart failure (all grades: 4.1%; grade ≥3: 2.5%) and ischemic heart disease (all grades: 1.8%; grade ≥3: 0.8%) - may lead to treatment suspensions. At present, there are neither prospective studies nor expert consensus on the prevention, monitoring and treatment of CVAEs in myeloma patients treated with carfilzomib.Methods: An expert panel of the European Myeloma Network in collaboration with the Italian Society of Arterial Hypertension and with the endorsement of the European Hematology Association aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk-benefit ratio of diagnostic and therapeutic tools, thereby achieving myeloma response with novel combination approaches whilst preventing CVAEs.Results: Patients scheduled to receive carfilzomib need a careful cardiovascular evaluation before treatment and an accurate follow-up during treatment.Conclusions: A detailed clinical assessment before starting carfilzomib treatment is essential to identify patients at risk for CVAEs, and accurate monitoring of blood pressure and of early signs and symptoms suggestive of cardiac dysfunction remains pivotal to safely administer carfilzomib without treatment interruptions or dose reductions. [ABSTRACT FROM AUTHOR]

The article discusses metformin therapy for the management of infertility in women with polycystic ovary syndrome (PCOS). Topics discussed include contribution of high levels of circulating insulin to excess androgen production and to anovulation; study comparing metformin with placebo in 320 women with PCOS and recommendation for the use of other insulin sensitisers such as thiazolidinediones.

The paper of the Change Process Study Group of Boston addresses an unsolved conceptual problem: How does one codify intersubjective states? The transfer of concepts from infant research to the adult therapeutic dyad is more than an analogy in that certain primitive aspects of mind appear in infancy, but persist throughout life. The regulation of consciousness is one salient example. The adult therapeutic dyad and the mother–infant dyad can be viewed as self-regulating dynamic systems that are also self-reparative. The concept of implicit relational knowledge is offered as an alternative way of thinking about internal object relations. © 1998 Michigan Association for Infant Mental Health [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses various reports published within the issue on topics including the shift from therapy as a healing relationship to therapy as the application of specific techniques, the specific nature of bureaucracy, and rituals that generate a feeling of mechanical repetition.

Idiopathic constipation in children can be difficult to manage with conventional therapies. The present study aimed to evaluate the efficacy of adjunctive botulinum toxin injection in children attending our regional centre with refractory idiopathic constipation associated with internal anal sphincter hypertonicity. Children suffering refractory constipation after a minimum of 3 months bowel training, dietary and laxative treatments were evaluated by anorectal manometry. Those with idiopathic anal sphincter hypertonicity (resting pressure > 60 mmHg with normal recto-anal reflex) were recruited for botulinum toxin injection. Pretreatment evaluation also included bowel-function score and the degree of megarectum as measured transpubically by ultrasound. Each child received 60 units of Botox intrasphincterically under general anaesthesia. Follow-up evaluations were carried out at 6 weeks and 6 months. Eleven Chinese children, mean age 6.1 years, underwent botulinum toxin treatment. The mean sphincter pressure decreased from 73 mmHg to 55 mmHg and the mean symptom score improved from 2.5 to 6.3 ( P = 0.003, Wilcoxon signed rank-sum test). The mean rectal diameter decreased from 3.7 cm to 3.4 cm. Findings were sustained at 6 months with no treatment complications. Botulinum toxin intrasphincteric injection is a safe, non-invasive and effective adjunct to conventional therapies in managing children with refractory idiopathic constipation associated with sphincter hypertonicity. Timely definitive therapy to facilitate pain-free habitual defecation plays an important role in these children in their potty training, as demonstrated by the sustained 'sphincterotomy' effects outlasting the transient toxin paralysis. [ABSTRACT FROM AUTHOR]

Background: miRNA‐based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity‐independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT‐ PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia. [ABSTRACT FROM AUTHOR]

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients’ inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis. [ABSTRACT FROM AUTHOR]

The article presents different studies related to a variety of internal medicines and respective illness that can be treated. These include the early warning score (EWS), which is considered a useful tool in detecting patients who deteriorate their clinical condition. Meanwhile, physicians should also address issues manifesting a poor vascular health. It also notes that benchmarking method have confounded the estimates of the treatment outcomes.

Comments on two research on pharmacologic therapy for prehypertension and therapeutic inertia as a barrier to blood pressure control. Blood pressure values of prehypertension; Results of the Trial of Preventing Hypertension that began in 1999; Definition of therapeutic inertia.

The article comments on the study "Prevention of Cardiovascular Events With an Antihypertensive Regimen of Amlodipine Adding Perindopril as Required Versus Atenolol Adding Bendroflumethiazide as Required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm: A Multicentre Randomised Controlled Trial," by B. Dahlof, P. S. Sever, N. R. Poulter and colleagues. It explains that the trial suggests that atenolol is not an acceptable therapy for the treatment hypertension. Further, it suggests that a strategy using a calcium channel blockers is more effective than the β-blocker atenolol. It argues that the trial was not a trial of combination agent therapy and should not be interpreted as such. It also states the blood pressure in the trial was poorly controlled.

Discusses several research on hypertension. Comments regarding the use of atenolol as a drug for hypertension; Cardiovascular benefits that can be derived from angiotensin-converting enzyme inhibit therapy by low-risk patients with coronary artery disease and preserved left ventricular function; Information on protection against fracture offered by beta blockers.

In the absence of an internationally agreed classification of haemorrhoids, evaluation of the ever increasing number of therapeutic options available is impossible. A new classification is proposed which relates symptoms to our knowledge of haemorrhoidal development, the use of which should provide a more accurate way of comparing treatments and in the evaluation of new techniques. The evidence for such a classification is presented in detail. [ABSTRACT FROM AUTHOR]

Dysregulation of fibroblast growth factor receptor 3 ( FGFR3) by the translocation t(4;14)(p16;q32) occurs in 15% of multiple myeloma (MM) patients and confers a growth and survival advantage to malignant plasma cells. As FGFR3 is a molecular target, we assessed the therapeutic potential of the FGFR-specific tyrosine kinase inhibitors SU5402 and SU10991 in MM. SU5402 inhibited FGFR3 phosphorylation in vitro and in murine MM tumour models. B cells dependent on FGFR3 for survival were specifically sensitive to SU5402. A panel of 11 human myeloma cell lines was studied, five bearing the t(4;14) translocation. The KMS11 human myeloma cell line, which expresses constitutively active mutant FGFR3, displayed an 85% decrease in S-phase cells, a 95% increase in G0/G1 cells, and 4·5-fold increase in apoptotic cells after 72 h treatment with 10 μmol/l SU5402. Activated extracellular signal-regulated kinases  1 and 2 and signal transducer and activator of transcription 3 were rapidly down-regulated after SU5402 treatment. In human myeloma cell lines expressing wild-type FGFR3 the stimulating effect of aFGF ligand was abrogated by SU5402 treatment. Myeloma cells lacking the t(4;14) or with the t(4;14) and a secondary RAS mutation did not respond to therapy. These findings support the development of clinical trials of early intervention with FGFR3 inhibitors in t(4;14) myeloma. [ABSTRACT FROM AUTHOR]

Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was set out to assess the functional properties of CD27 expressed on PCL plasma cells by triggering with its ligand CD70. Using CD27-expressing purified plasma cells from a PCL patient we demonstrated that CD27-triggering modestly inhibited spontaneous and dexamethasone-induced apoptosis. In vitro stimulation and Western blotting showed that activation of p38 and extracellular-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPK) was associated with CD27-mediated signal transduction. Specific inhibition of p38 and ERK1/2 MAPK abolished the anti-apoptotic effects of CD27-triggering. Interestingly, simultaneous inhibition of p38 and ERK1/2 strongly sensitized PCL cells for dexamethasone-induced apoptosis. Finally, in dexamethasone-treated PCL cells, CD27-triggering was associated with persistent DNA-binding activity of activator protein 1 (AP-1) but not of nuclear factor- κB. These findings suggest that, in primary PCL, specific anti-apoptotic pathways exist that might provide novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Our objective was to test a theoretical model that explains quality of life as a function of the intrusiveness of illness encroaching on the different domains of one’s life. The intrusiveness of illness is explained not only by disease and treatment related factors, but also by one’s psychological and social resources (Devins, 1994). To investigate this issue, a sample of 336 women aged 50 and under, recently diagnosed with breast cancer were interviewed in their homes. Consistent with Devins’ model, intrusiveness of illness mediated the effect of disease and treatment factors on quality of life. Contrary to his model, some treatment factors also had direct effects while social and psychological factors had only direct effects on quality of life. Neither time post-diagnosis nor type of treatment affected the psychological component of quality of life. © 1998 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses the role of salpingopharyngostomy in treating certain cases of guttural pouch mycosis in horses. Topics discussed include treatment of fibrotic myopathy; tenotomy of the semitendinosus muscle in horses with fibrotic myopathy; and the issues relating to the Inflammatory disease.

Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in‐depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation. [ABSTRACT FROM AUTHOR]

Objectives: A prospective parallel cohort trial was conducted to compare outcomes of patients treated with maxillary protraction vs LeFort 1 maxillary advancement surgery.Setting and Sample Population: The primary site for the clinical trial is Children's Hospital Los Angeles; the satellite test site is Seattle Children's Hospital. All patients have isolated cleft lip and palate and a skeletal Class III malocclusion.Material and Methods: A total of 50 patients, ages 11-14, will be recruited for the maxillary protraction cohort. The maxillary surgery cohort consists of 50 patients, ages 16-21, who will undergo LeFort 1 maxillary advancement surgery. Patients with additional medical or cognitive handicaps were excluded from the study.Results: Current recruitment of patients is on track to complete the study within the proposed recruitment period.Conclusion: This observational trial is collecting information that will examine dental, skeletal, financial and quality-of-life issues from both research cohorts. [ABSTRACT FROM AUTHOR]

Reviews of several articles related to prevalence of headshaking, efficacy of ivermectin (IVE) and moxidectin (MOX) on faecal egg counts, and bronchopneumonia treatment with tulathromycin which appeared in the previous issue of the periodical, were presented.

Background Internal anal sphincter tone depends on the intrinsic myogenic properties of smooth muscle and external neural influences, specifically a continuous sympathetic input. Reduction of maximum resting anal canal pressure (MRP) increases the vascularity of ischaemic chronic anal fissures and promotes healing. Methods Ten patients with chronic anal fissures (median age 35.5 (28-65) years) and 10 healthy volunteers (median age 28 (21-38) years) were administered 20 mg indoramin (α[sub 1]-antagonist) or 4 mg salbutamol (&beta[sub 2]-agonist) orally in a doubleblinded manner. MRP, pulse, and blood pressure were measured prior to and at hourly intervals until 3 h after administration. Results Patients with chronic anal fissures had a significantly higher MRP compared with volunteers (P < 0.05, MannWhitney U-test). In each group there was a significant reduction in MRP at 1, 2 and 3 h (P < 0.05, Wilcoxon signed ranks test). Indoramin and salbutamol demonstrated no significant difference in effect when comparing reduction of MRP in patients and volunteers (Mann-Whitney U-test). The reduction in patients' MRP at 3 h was comparable to that after lateral sphincterotomy. Tremors were noted with salbutamol in four volunteers, and five patients. Three patients complained of light-headedness with indoramin without a significant change in diastolic blood pressure. The reduction in MRP in subjects who took indoramin did not correlate with a reduction in diastolic blood pressure (Pearson correlation coefficient, r = 0. 166, P = NS). Conclusion Oral indoramin causes a sustained reduction in MRP, without serious side effects, and may have a beneficial role in the treatment of anal fissures. (MRP - maximum resting anal canal pressure). [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients. In this review, past and present management is discussed based on a comprehensive literature search. A treatment algorithm is presented based on available evidence and our overall clinical experience. In addition, unmet needs with regard to treatment are highlighted and discussed. We describe the development of various treatment options for IPF from the first consensus to recent guidelines based on evidence from large-scale, multinational, randomized clinical trials, which have led to registration of the first drugs for IPF. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Comparison of Methods for the Repair of Acute Tympanic Membrane Perforations: Silk Patch vs Paper Patch" by J.Kim et al.

Progression‐free survival (PFS) is an important clinical metric for comparing and evaluating similar treatments for the same disease within oncology. After the completion of a clinical trial, a descriptive analysis of the patients' PFS is often performed post hoc using the Kaplan–Meier estimator. However, to perform predictions, more sophisticated quantitative methods are needed. Tumor growth inhibition models are commonly used to describe and predict the dynamics of preclinical and clinical tumor size data. Moreover, frameworks also exist for describing the probability of different types of events, such as tumor metastasis or patient dropout. Combining these two types of models into a so‐called joint model enables model‐based prediction of PFS. In this paper, we have constructed a joint model from clinical data comparing the efficacy of FOLFOX against FOLFOX + panitumumab in patients with metastatic colorectal cancer. The nonlinear mixed effects framework was used to quantify interindividual variability (IIV). The model describes tumor size and PFS data well, and showed good predictive capabilities using truncated as well as external data. A machine‐learning guided analysis was performed to reduce unexplained IIV by incorporating patient covariates. The model‐based approach illustrated in this paper could be useful to help design clinical trials or to determine new promising drug candidates for combination therapy trials. [ABSTRACT FROM AUTHOR]

Background: People with motor neuron disease (pwMND) are routinely offered gastrostomy feeding tube placement and (non‐invasive and invasive) ventilation to manage the functional decline associated with the disease. This study aimed to synthesise the findings from the qualitative literature to understand how individual, clinical team and organisational factors influence pwMND decisions about these interventions. Methods: The study design was guided by the enhancing transparency in reporting the synthesis of qualitative research (ENTREC) statement. The search of five bibliography databases and an extensive supplementary search strategy identified 27 papers that included qualitative accounts of pwMND, caregivers and healthcare professionals' (HCPs) experiences of making decisions about gastrostomy and ventilation. The findings from each study were included in a thematic synthesis. Findings: Making decisions about interventions is an emotional rather than simply a functional issue for pwMND. The interventions can signal an end to normality, and increasing dependence, where pwMND consider the balance between quality of life and extending survival. Interactions with multiple HCPs and caregivers can influence the process of decision‐making and the decisions made. These interactions contribute to the autonomy pwMND are able to exert during decision‐making. HCPs can both promote and threaten pwMND perceived agency over decisions through how they approach discussions about these interventions. Though there is uncertainty over the timing of interventions, pwMND who agree to interventions report reaching a tipping point where they accept the need for change. Conclusion: Discussion of gastrostomy and ventilation options generate an emotional response in pwMND. Decisions are the consequence of interactions with multiple external agents, including HCPs treading a complex ethical path when trying to improve health outcomes while respecting pwMND right to autonomy. Future decision support interventions that address the emotional response and seek to support autonomy have the potential to enable pwMND to make informed and timely decisions about gastrostomy placement and ventilation. Patient or Public Contribution: The lead author collaborated with several patient and participant involvement (PPI) groups with regards to the conceptualisation and design of this project. Decisions that have been influenced by discussions with multiple PPI panels include widening the scope of decisions about ventilation in addition to gastrostomy placement and the perceptions of all stakeholders involved (i.e., pwMND, caregivers and HCPs). [ABSTRACT FROM AUTHOR]

Background: For acute cholecystitis in the latter 19th century and early 20th century, the diagnosis was difficult and the management not defined. Methods and Results: Bernhard Riedel of Jena in Germany documented his patients, analysed his results, and described his method of cholecystectomy. Conclusions: Riedel advocated early operation for acute cholecystitis when the conditions were favourable, as for acute appendicitis. He stressed the importance of good lighting, an experienced surgeon and trained assistants. He advocated conservative treatment for minor cholecystitis (biliary colic) until the diagnosis was certain, followed by elective cholecystectomy to reduce the risk of subsequent acute cholecystitis or bile duct stones. Caution was advised when analysing previous statistics, to ensure appropriate patient comparison. [ABSTRACT FROM AUTHOR]

This document provides abstracts of papers presented at the 2024 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. The papers cover a wide range of topics related to clinical pharmacology and therapeutics, including the use of machine learning in predicting adverse events, the integration of brain- and blood-derived markers in antidepressant pharmacotherapy, and the use of NLP-powered topic modeling in drug repurposing. Other studies focused on the pharmacokinetics and safety of different drugs, the development of population pharmacokinetic models, and potential drug-drug interactions involving cannabidiol. These studies offer valuable insights into drug behavior and can help guide personalized treatment strategies in different populations. The document also discusses the use of computational tools and machine learning techniques to improve drug pharmacokinetics and clinical trial design. Overall, these studies contribute to our understanding of how drugs interact with the body and can inform more effective and personalized treatment approaches. [Extracted from the article]

This paper examines cyberbullying concerning therapeutic interventions. A section on bullying and how bullying impacts the therapeutic environment is included. The author provides his definition of bullying to incorporate cyberbullying and how it is no longer a "new issue" but an evolving one. The current status of therapeutic interventions used to support victims of cyberbullying has been explored, emphasising their effectiveness in assisting those experiencing bullying. A segment has been implemented to comprehend whether practitioners fully understand the potential implications of cyberbullying on clients, whether bullying is still seen as a "rite of passage" and what the possible consequences of this could be. Peer interventions and support groups concerning cyberbullying have been referenced, including The KiVa Programme, the Shared Concern Method and The Circle of Friends Method. These have highlighted specific examples of therapeutic and nontherapeutic approaches to intervene with cyberbullying. A section on potential further training is presented for practitioners working within educational environments. Moreover, physical, psychological, sexual and relational bullying are discussed in the article when applicable, with the umbrella term "bullying" used to discuss all forms of bullying at once. The paper has uncovered two key messages: (1) cyberbullying requires more awareness in counselling and is no longer a new issue and (2) more extensive training is required to assist therapists to work with cyberbullying victims. [ABSTRACT FROM AUTHOR]

Background: Research is beginning to shed light on the practices employed by speech‐language therapists (SLTs) for the management of acquired dysarthria. However, studies that explore SLTs' satisfaction with the effectiveness of current therapies and their interest in new treatment methods for this population have not been carried out. One potential new method is neuromuscular electrical stimulation (NMES): the pool of evidence for its use in rehabilitation is increasing, yet it has not been widely explored for use with dysarthria. Aim: To extend the understanding of acquired dysarthria management practices employed by SLTs across the globe and determine their satisfaction with current therapy options. To explore their interest in using NMES with this population. Methods and Procedures: A cross‐sectional international online survey was developed and disseminated to SLTs working with adults with acquired dysarthria through international professional associations. The survey collected information on demographic characteristics, dysarthria management practices, satisfaction with treatment effectiveness and interest in and knowledge of NMES. Survey responses were analysed using descriptive and inferential statistics, and quantitative content analysis. Outcomes and Results: A total of 211 SLTs (North America, 48.8%; Europe, 36%; Asia, 8.1%; Oceania, 5.7%; Africa, 0.9%; South America, 0.5%) completed the survey in full. Management practices varied considerably. There was a clear preference for informal assessments, mainly oral‐motor examinations, focusing on body functions and structures. The majority of respondents rejected the use of non‐speech oral motor exercises as a clinical or carryover exercise. Variable satisfaction with current speech subsystem treatments was noted; however, overall, there was a general dissatisfaction. Whilst a strong interest in the use of NMES for dysarthria was evidenced, it was noted that most SLTs lacked fundamental knowledge of NMES principles and application. Conclusion: SLTs' management practices and satisfaction with acquired dysarthria treatments differed substantially. Investigations of the potential use of NMES for dysarthria treatment are of interest. WHAT THIS PAPER ADDS: What is already known on the subject: Recent country‐specific surveys have explored speech‐language therapists' (SLTs') assessment and intervention practices for acquired dysarthria. These studies indicate that although clinical management for this speech disorder mainly involves informal assessment tools and impairment‐focused treatment, communication beyond the impairment, such as the activity and participation domains, is also frequently assessed and treated. What this paper adds to existing knowledge: The majority of SLTs are dissatisfied with the overall benefits of current acquired dysarthria treatment. Phonatory, respiration and speech rate therapies are perceived to be more effective than prosody, articulation and resonance treatments. Despite a general lack of theoretical knowledge, most SLTs are interested in neuromuscular electrical stimulation treatment for acquired dysarthria. What are the potential or actual clinical implications of this work?: New, evidence‐based treatments are needed for SLTs to be confident in the effectiveness of their acquired dysarthria treatment. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a growing paediatric clinical emergency that is difficult to diagnose because a consensus definition was lacking until recently. Many European countries have no specific guidelines for anaphylaxis. This position paper prepared by the EAACI Taskforce on Anaphylaxis in Children aims to provide practical guidelines for managing anaphylaxis in childhood based on the limited evidence available. Intramuscular adrenaline is the acknowledged first-line therapy for anaphylaxis, in hospital and in the community, and should be given as soon as the condition is recognized. Additional therapies such as volume support, nebulized bronchodilators, antihistamines or corticosteroids are supplementary to adrenaline. There are no absolute contraindications to administering adrenaline in children. Allergy assessment is mandatory in all children with a history of anaphylaxis because it is essential to identify and avoid the allergen to prevent its recurrence. A tailored anaphylaxis management plan is needed, based on an individual risk assessment, which is influenced by the child’s previous allergic reactions, other medical conditions and social circumstances. Collaborative partnerships should be established, involving school staff, healthcare professionals and patients’ organizations. Absolute indications for prescribing self-injectable adrenaline are prior cardiorespiratory reactions, exercise-induced anaphylaxis, idiopathic anaphylaxis and persistent asthma with food allergy. Relative indications include peanut or tree nut allergy, reactions to small quantities of a given food, food allergy in teenagers and living far away from a medical facility. The creation of national and European databases is expected to generate better-quality data and help develop a stepwise approach for a better management of paediatric anaphylaxis. [ABSTRACT FROM AUTHOR]

Objective: Acromegaly is a condition characterized by an overproduction of growth hormone which infers high morbidity and mortality if left untreated. The objective of this review is to analyse and appraise the current evidence for the generalized use of preoperative medications and the various surgical approaches as described in the literature. Design: A thorough search from MEDLINE via PubMed, EMBASE, and Cochrane Library has been performed which identified a total of 37 papers. Conclusion: The preoperative use of somatostatin receptor agonists (SAs) in acromegaly is a controversial topic with current guidelines suggesting against their generalized routine use. Most authors noticed an insignificant long‐term remission of acromegaly when given SAs compared with nil preoperative therapy, except for invasive macroadenomas as SAs have been found to reduce the tumour volume and aid towards the total resection of the adenoma. Furthermore, according to the evidence available, endoscopic transsphenoidal surgery is the optimum method for hypophysectomy in terms of its remission and safety profile. [ABSTRACT FROM AUTHOR]