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Objective: Patients taking antiresorptive medications in dental clinics are at risk of medication-related osteonecrosis of the jaw (MRONJ), which poses daily challenges for their clinicians. This paper aimed to summarize and revisit the three most recognized practice guidelines for the management and prevention of MRONJ, which were proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), and presented by the Journal of Bone and Mineral Research (JBMR) and the Journal of Clinical Oncology (JCO). Results and case studies: The AAOMS position paper focused on risk stratification by different medications, management decision trees, risk factors, pathophysiology, and disease staging. The JBMR international consensus presented eight focused questions, which were addressed by systematic reviews. The JCO clinical practice guideline presented six clinical questions, and each concluded with practical recommendations. Practical information was summarized and converted into an adoptable patient care workflow for clinicians to follow and apply in daily practice. Three case studies presented were treated following these guidelines. Each patient underwent advanced surgeries including alveoloplasty, tooth extraction, implant placement, and particulate bone grafting. Some of the considerations not fully informed were discussed and illustrated in each step of the patient care workflow, which included specifics for risk communication, updates on the use of antibiotics, biomarkers, and drug holidays. Conclusion and practical implications: Structured risk communication with official informed consent documentation should be considered before initiating invasive treatments. Disease control phase with home care therapy should be provided prior to staged reconstructive therapy. Drug holidays and antibiotics coverage can be customized based on individual conditions and related procedures with interprofessional coordination. [ABSTRACT FROM AUTHOR]

ABSTRACT We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg‐positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg‐positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0‐1 and S0‐1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754–0.809) than the EASL (AUC 0.765, 95% CI 0.737–0.793), AASLD (AUC 0.749, 95% CI 0.720–0.778) and APASL (AUC 0.720, 95% CI 0.690–0.750) criteria for identifying G0‐1 and S0‐1. Adding quantitative HBsAg levels (> 104 IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg‐positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg‐positive chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background: Additional surgery with lymph node (LN) dissection is recommended for pT1 colorectal carcinoma (CRC) resected by endoscopy, based on pathological risk factors for LN metastasis (LNM), according to guidelines by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO). Methods: We retrospectively analyzed 560 consecutive patients with T1 CRC who underwent endoscopic resection alone (n=190) or initial or additional surgery with LN dissection (n=370) between 1992 and 2017 at Hiroshima University Hospital. Patients were classified into LNM low- and high-risk groups according to guidelines by the JSCCR, NCCN, and ESMO as follows. Patients without any specified pathological LNM risk factor were included in the LNM low-risk group, while the high-risk group comprised all other patients. We analyzed the LNM predictive ability of each guideline. Results: The LNM high-risk rate, sensitivity, specificity, positive and negative predictive values, accuracy of LNM risk, and AUC for LNM predictive ability were 82%, 100%, 19%, 9%, 100%, 26% and 0.596 in the JSCCR guidelines; 52%, 98%, 52%, 15%, 99%, 56%, and 0.749 in the NCCN; and 54%, 98%, 50%, 15%, 99%, 54%, and 0.743 in the ESMO, respectively. Conclusions: The JSCCR guidelines could diagnose LNM in all cases but had the highest false-positive rate. It is important to reduce unnecessary additional surgeries for pT1 CRCs after ER. [ABSTRACT FROM AUTHOR]

Objective: To develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA). Method: A joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated. Results: A total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients' values and willingness as well as the objective of testing in the local context. Conclusion: This guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionsA chronic subdural haematoma (cSDH) is an encapsulated collection of fluid and blood degradation products in the subdural space. It is increasingly common, affecting older people and those living with frailty. Currently, no guidance exists to define optimal care from onset of symptoms through to recovery. This paper presents the first consensus-built recommendations for best practice in the care of cSDH, co-designed to support each stage of the patient pathway.Guideline development was led by a multidisciplinary Steering Committee with representation from diverse clinical groups, professional associations, patients, and carers. Literature searching to identify relevant evidence was guided by core clinical questions formulated through facilitated discussion with specially convened working groups. A modified Delphi exercise was undertaken to build consensus on draft statements for inclusion in the guideline using survey methodology and an in-person meeting. The proposed guideline was subsequently endorsed by the Society for British Neurological Surgeons, Neuroanaesthesia and Critical Care Society, Association of Anaesthetists, British Association of Neuroscience Nurses, British Geriatric Society, and Centre for Perioperative Care.We identified that high quality evidence was generally lacking in the literature, although randomised controlled trial (RCT) data were available to inform specific recommendations on aspects of surgical technique and use of corticosteroids. The final guideline represents the outcome of synthesising available evidence, consensus-built expert opinion and patient involvement. The guideline comprises 67 recommendations across eight major themes, covering: presentation and diagnosis, neurosurgical triage and shared decision-making, non-operative management, perioperative management (including anticoagulation), timing of surgery, intraoperative and postoperative care, rehabilitation and recovery.We present the first multidisciplinary guideline for the care of patients with cSDH. The recommendations reflect a paradigm shift in the care of cSDH, recognising and formalising the need for multidisciplinary and collaborative clinical management, communication and decision-making delivered effectively across secondary and tertiary care. [ABSTRACT FROM AUTHOR]

Patients with epilepsy often require long‐term treatment with antiseizure medications, and their impact on daily activities, particularly driving, is of significant concern. The recently published “Guideline for Evaluating Effects of Psychotropic Drugs on the Performance to Drive a Motor Vehicle” in Japan provides a framework that can be referred to for not only the evaluation of new drugs but also the reevaluation of approved drugs. This study conducted a literature review regarding the effects of carbamazepine, valproate, lamotrigine, lacosamide, and levetiracetam, which are frequently prescribed for epilepsy, on driving performance following the guideline's tiered evaluation approach. Analyses of pharmacological, pharmacodynamic, and adverse events suggested that these drugs primarily affect arousal function. Driving studies showed that acute administration of carbamazepine, but not chronic monotherapy with carbamazepine, valproate, lamotrigine, and levetiracetam, significantly impairs driving performance. Epidemiological studies have not identified a definitive association between these drugs and traffic accidents. Initial administration of these five antiseizure medications may affect driving performance, warranting special attention, but the influence appears to diminish with continued use. Nevertheless, while long‐term administration of these five drugs may not have a clinically meaningful effect on driving performance, safe driving is not guaranteed for each individual patient, and appropriate individualized guidance is important in clinical practice. [ABSTRACT FROM AUTHOR]

Background and objective: Cognitive impairment and dementia as well as affective disorders are common and debilitating syndromes that develop in people with Parkinson's disease (PwPD). The authors summarized recommendations for the 2023 updated German guidelines on "Parkinson's disease" from the German Neurological Society (DGN), focusing on the diagnosis and treatment of these disorders. Methods: The recommendations were based on literature reviews, other relevant guidelines, and expert opinions. Results: Measurements to assess cognitive and affective states were reviewed for psychometric properties, use in routine clinical practice, and availability in German. To improve mild cognitive impairment, cognitive training and physical aerobic training are recommended. To treat Parkinson's disease (PD)-related dementia, cognitive stimulation (as a non-pharmacological intervention) and acetylcholinesterase inhibitors (AChEIs, i.e., rivastigmine) are recommended. Cognitive behavioral therapy is recommended to treat depression, anxiety, and fear of progression. Physical interventions are recommended to treat depression, fatigue, and apathy. Optimized dopaminergic treatment is the first-line pharmacological strategy recommended to manage depression, apathy, anhedonia, fatigue, and mood swings. Major depression can be additionally treated using venlafaxine or desipramine, while moderate depression can be treated pharmacologically according to its clinical phenotype (psychomotor retardation or agitation) and comorbidities (e.g., sleep disturbances, pain). Venlafaxine and nortriptyline can be used to treat anhedonia, while citalopram can be used for anxiety. Conclusions: In addition to the updated pharmacological treatment options, new insights into recommendations for standardized diagnostics and non-pharmacological interventions were provided for the German health care system. However, more studies are needed to explore the full potential of non-pharmacological interventions to treat and prevent cognitive impairment and affective disorders. [ABSTRACT FROM AUTHOR]

Objectives: Preschooler physical activity (PA) is vital for growth and development. The World Health Organization PA guidelines state preschoolers should achieve ≥ 180 min/day of Total PA (TPA) of which ≥ 60 min is moderate‐to‐vigorous PA (MVPA). A step/day recommendation to match these guidelines may be a more practical metric for caregivers to promote PA. The purpose of our investigation is to improve upon existing step recommendations by creating one for indoor‐based activities, acknowledging where preschoolers spend most of their time, and various cut‐points for PA. Methods: In a laboratory study (Aim 1), a validated direct observation protocol was used to quantify preschooler PA intensity while performing indoor activities (n = 35). Actigraph GT3x accelerometers were placed on the waist, wrist, and ankle to measure step count. In a field study (Aim 2), habitual PA of 881 preschoolers (7113 valid days) via waist‐worn accelerometers was used to assess the agreement between created guidelines (Aim 1) and other step recommendations with PA guidelines using Receiver Operating Characteristic and Area Under the Curve (ROC‐AUC). Results: In the laboratory study, calculated indoor step ranges were 6960–7440 (waist), 7200–8640 (wrist), and 7680–9120 (ankle) to align with existing PA guidance. In the field, the higher step guidelines (> 12 000) achieved very limited agreement, due to few preschoolers achieving this metric. The 6000 step/day guidelines had the highest agreement (AUCs: TPA: 0.637; MVPA: 0.751; TPA + MVPA: 0.761) with PA guideline. Conclusions: When preschoolers are indoors, 6000 steps may be the minimum for adequate PA. [ABSTRACT FROM AUTHOR]

This guideline was developed according to the British Society for Rheumatology Guidelines Protocol by a Guideline Development Group comprising healthcare professionals with expertise in SSc and people with lived experience, as well as patient organization representatives. It is an update of the previous 2015 SSc guideline. The recommendations were developed and agreed by the group and are underpinned by published evidence, assessed by systematic literature review and reinforced by collective expert opinion of the group. It considers all aspects of SSc including general management, treatment of organ-based complications, including cardiopulmonary, renal and gastrointestinal tract manifestations, as well as broader impact of disease. Whilst it is focused on adults with SSc we expect that the guideline will be relevant to people of all ages and expert input and review by paediatric rheumatologists and other relevant specialists considered where the guideline was, or may not be, applicable to young people with SSc and juvenile-onset disease. In addition to providing guidance on disease assessment and management the full guideline also considers service organization within the National Health Service and future approaches to audit of the guideline. The lay summary that accompanies this abstract can be found in Supplemental information 1. [ABSTRACT FROM AUTHOR]

The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment. The larger the variability of the imaging endpoint, the more animals are needed to be able to observe statistically significant differences between groups. Therefore, preclinical imaging requires quality control procedures to maintain reliability, reproducibility, and repeatability of imaging procedures, and to ensure the accuracy and precision of SPECT and PET quantification. While the Physics Committee of the European Association of Nuclear Medicine (EANM) has already published excellent procedure guidelines for Routine Quality Control Recommendations for Nuclear Medicine Instrumentation that also includes procedures for small animal PET systems, and important steps have already been made concerning preclinical quality control aspects, this new guideline provides a review and update of these previous guidelines such that guidelines are also adapted to new technological developments. [ABSTRACT FROM AUTHOR]

The article offers information on evidence-based approaches for treating obsessive-compulsive disorder (OCD) as outlined in the latest clinical guideline. Topics discussed include the evolution of OCD's classification in the DSM-5; the effectiveness of cognitive-behavioral therapy (CBT) as a frontline treatment; and the incorporation of recent advances in therapeutic practices and access to treatment.

Female hypogonadism (FH) is a relatively common endocrine disorder in women of premenopausal age, but there are significant uncertainties and wide variation in its management. Most current guidelines are monospecialty and only address premature ovarian insufficiency (POI); some allude to management in very brief and general terms, and most rely upon the extrapolation of evidence from the studies relating to physiological estrogen deficiency in postmenopausal women. The Society for Endocrinology commissioned new guidance to provide all care providers with a multidisciplinary perspective on managing patients with all forms of FH. It has been compiled using expertise from Endocrinology, Primary Care, Gynaecology and Reproductive Health practices, with contributions from expert patients and a patient support group, to help clinicians best manage FH resulting from both POI and hypothalamo‐pituitary disorders, whether organic or functional. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the capacity of chat-generative pre-trained transformer (Chat-GPT) to understand the S2k guideline of the German Society for Gynecology and Obstetrics on intrauterine growth restriction. Methods: The German-language free Chat-GPT version was used to test the ability of Chat-GPT to understand the definition of small for gestational age and intrauterine growth restriction, to indicate the correct time and place of delivery and to evaluate ist ability to recommend a spontaneous delivery versus a primary caesarean section in accordance with the guideline recommendations. In order to objectively evaluate the suggestions a simple three-color 'traffic light' evaluation system was employed. Results: Almost all Chat-GPT's suggestions in the context of definition of small for gestational age/intrauterine growth restriction as well as correct time of delivery were adequate, whereas more than half of the suggestions made in terms of correct delivery mode needed reformulation or even correction. Conclusion: Chat-GPT appears to be a valuable form of artificial intelligence that could be integrated into everyday clinical practice. [ABSTRACT FROM AUTHOR]

This European Society of Clinical Microbiology and Infectious Diseases guideline provides evidence-based recommendations to support a selection of appropriate antibiotic use practices for patients seen in the emergency department (ED) and guidance for their implementation. The topics addressed in this guideline are (a) Do biomarkers or rapid pathogen tests improve antibiotic prescribing and/or clinical outcomes? (b) Does taking blood cultures in common infectious syndromes improve antibiotic prescribing and/or clinical outcomes? (c) Does watchful waiting without antibacterial therapy or with delayed antibiotic prescribing reduce antibiotic prescribing without worsening clinical outcomes in patients with specific infectious syndromes? (d) Do structured culture follow-up programs in patients discharged from the ED with cultures pending improve antibiotic prescribing? An expert panel was convened by European Society of Clinical Microbiology and Infectious Diseases and the guideline chair. The panel selected in consensus the four most relevant antimicrobial stewardship topics according to pre-defined relevance criteria. For each main question for the four topics, a systematic review was performed, including randomized controlled trials and observational studies. Both clinical outcomes and stewardship process outcomes related to antibiotic use were deemed relevant. The literature searches were conducted between May 2021 and March 2022. In April 2022, the panel members were formally asked to suggest additional studies that were not identified in the initial searches. Data were summarized in a meta-analysis if possible or otherwise summarized narratively. The certainty of the evidence was classified according to the Grading of Recommendations Assessment, Development and Evaluation criteria. The guideline panel reviewed the evidence per topic critically appraising the evidence and formulated recommendations through a consensus-based process. The strength of the recommendations was classified as strong or weak. To substantiate the implementation process, implementation trials or observational studies describing facilitators/barriers for implementation were identified from the same searches and were summarized narratively. The recommendations on the use of biomarkers and rapid pathogen diagnostic tests focus on the initiation of antibiotics in patients admitted through the ED. Their effect on the discontinuation or de-escalation of antibiotics during hospital stay was not reported, neither was their effect on hospital infection prevention and control practices. The recommendations on watchful waiting (i.e. withholding antibiotics with some form of follow-up) focus on specific infectious syndromes for which the primary care literature was also included. The recommendations on blood cultures focus on the indication in three common infectious syndromes in the ED explicitly excluding patients with sepsis or septic shock. Most recommendations are based on very low and low certainty of evidence, leading to weak recommendations or, when no evidence was available, to best practice statements. Implementation of these recommendations needs to be adapted to the specific settings and circumstances of the ED. The scarcity of high-quality studies in the area of antimicrobial stewardship in the ED highlights the need for future research in this field. [ABSTRACT FROM AUTHOR]

Objective: Ischemic stroke is a significant cause of disability and death worldwide. Randomized clinical trials (RCTs) are important in changing guidelines and treatment strategies. This study aimed to analyze the progress of RCTs in ischemic stroke and to guide future research directions. Methods: Ischemic stroke‐related RCT articles were identified in six high‐impact medical journals using the Web of Science Core Collection database. Google Scholar was used to check whether relevant articles were included in the guidelines. The characteristics of these articles were analyzed and future research hotspots were predicted. Results: 389 relevant articles were included in the analysis. The number of articles increased rapidly from 1972 to 2022, from 5 (1.3%; 1972–1982) to 208 (53.5%; 2013–2022) articles. 338 (86.9%) articles were included in relevant guidelines. According to corresponding author location, Europe was the source of the highest number of publications (183; 47.0%), followed by the Americas (152; 39.1%) and the Western Pacific (54; 13.9%). The number of publications steadily increased over time in the USA, England, Canada, Australia, Germany, and France, and surged in China and Spain, especially in the last 5 years. In recent years, endovascular therapy has accounted for the majority of ischemic stroke‐related RCT articles. Conclusions: Numerous RCTs related to ischemic stroke have been conducted in recent decades, and both the number of articles and their contribution to guideline updates are increasing. Also, a shift in research topics was observed. However, great regional imbalances in this research exist, calling for more research to be conducted in specific regions to promote the generalizability of trial conclusions. [ABSTRACT FROM AUTHOR]

The Canadian Association of Radiologists (CAR) Cardiovascular Expert Panel is made up of physicians from the disciplines of radiology, cardiology, and emergency medicine, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 30 clinical/diagnostic scenarios, a rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 48 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 125 recommendation statements across the 30 scenarios (27 unique scenarios as 2 scenarios point to the CAR Thoracic Diagnostic Imaging Referral Guideline and the acute pericarditis subscenario is included under 2 main scenarios). This guideline presents the methods of development and the referral recommendations for acute chest pain syndromes, chronic chest pain, cardiovascular screening and risk stratification, pericardial syndromes, intracardiac/pericardial mass, suspected valvular disease cardiomyopathy, aorta, venous thrombosis, and peripheral vascular disease. [ABSTRACT FROM AUTHOR]

The increasing global drug shortage poses a substantial challenge to national healthcare systems and affects access to essential therapies. In Japan, this problem is exacerbated by a large-scale government campaign to switch from brand-name products to generic drugs and manufacturing/marketing authorization holders with poor development and manufacturing controls. Regulatory bodies, such as the U.S. Food and Drug Administration and the European Medicines Agency have developed guidelines aimed at ensuring continuous drug supply and mitigating manufacturing risks. However, Japan's efforts have primarily relied on voluntary industry guidelines, lacking the robust regulatory frameworks of other developed nations. Therefore, this study proposes a draft guideline for Japan's pharmaceutical industry to manage drug shortages effectively. The Japanese government needs to establish a framework system that will enable pharmaceutical companies to effectively maintain a stable supply based on the proposals developed in this study. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the fourth most common cancer and the fourth leading cause of mortality in women worldwide. It is strongly associated with high-risk human papillomavirus infection. High-income countries that have implemented human papillomavirus (HPV) vaccination and screening programs have seen dramatic reductions in CC incidence, while developing countries where these programs are not available continue to experience high rates of CC deaths. In early-stage CC, the primary treatment is surgery or radiotherapy, whereas concurrent chemo-radiotherapy (CRT) remains the conventional approach in locally advanced stages until the upcoming approval of immunotherapy. The incorporation of immunotherapy in combination with chemotherapy (with or without bevacizumab) in first line and as monotherapy in second line after platinum-based chemotherapy, has significantly increased overall survival (OS) in recurrent or metastatic CC. The purpose of this guideline is to summarize the most relevant evidence in the diagnosis, treatment, and follow-up of CC and to provide evidence-based recommendations for clinical practice. [ABSTRACT FROM AUTHOR]

In recent years, the incorporation of new strategies to the therapeutic armamentarium has completely changed the outcomes of epithelial ovarian cancer (EOC). The identification of new predictive and prognostic biomarkers has also enabled the selection of those patients more likely to respond to targeted agents. Nevertheless, EOC is still a highly lethal disease and resistance to many of these new agents is common. The objective of this guideline is to summarize the most relevant strategies to manage EOC, to help the clinician throughout the challenging diagnostic and therapeutic processes and to provide evidence-based recommendations. [ABSTRACT FROM AUTHOR]

The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis. Though slow-growing and having a low proliferative index, grade 2 gliomas are incurable by surgery and complementary treatments are vital to improving prognosis. This guideline provides recommendations on the multidisciplinary treatment of grade 2 astrocytomas and oligodendrogliomas based on the best evidence available. [ABSTRACT FROM AUTHOR]

The development of the ulnar collateral ligament (UCL) guideline was undertaken in accordance with the British Society for Surgery of the Hand Evidence for Surgical Treatment (BEST) Process Manual, which has been accredited by the National Institute for Health and Care Excellence, UK. This review article serves as a summary of the systematic reviews and the final guideline. The group included two patients, a radiologist, a commissioner, an emergency medicine doctor, hand therapists and hand surgeons. The group's recommendations are that patients with acute UCL injuries should be assessed with a history, clinical examination and radiographs. Patients without significant joint laxity can be treated non-surgically. Patients with significant joint laxity on clinical examination may be treated with non-surgical joint immobilization or surgical repair and should reach a shared decision with their clinician about the definitive treatment within 2 weeks of presentation. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is the most common childhood intraocular malignancy. Delayed presentation due to a lack of awareness and advanced intraocular tumors are a common scenario in low-middle income countries (LMICs). Remarkable treatment advances have been made in the past few decades allowing globe salvage in advanced intraocular RB (IORB) including systemic chemotherapy with focal consolidation and targeted treatments like intraarterial chemotherapy and intravitreal chemotherapy. However, a lack of availability and affordability limits the use of such advances in LMICs. External beam radiotherapy, despite risk of second cancers in RB with germline mutations, still remains useful for recalcitrant RB not responding to any other treatment. When choosing conservative treatment for advanced IORB, the cost and long duration of treatment, morbidity from multiple evaluation under anesthesias (EUAs), side effects of treatment and risk of treatment failure need to be taken into account and discussed with the parents. In this article, the authors discuss the ICMR consensus guidelines on the management of IORB. [ABSTRACT FROM AUTHOR]

Background: In accordance with the guidelines of the Association of Scientific Medical Societies in Germany (AWMF), the DEGAM ("Deutsche Gesellschaft für Allgemeinmedizin") S1 guideline "Chronic pain" required updating. Methods: A selective nonsystematic literature search was performed and comments from the DEGAM guideline commission were obtained. Results: The content of the previous version can largely be maintained. The content was expanded, particularly in the areas of assessment, nondrug therapy approaches and self-care and opioid management. The short version was supplemented by a document with explanations and implementation aids. Conclusions: Chronic noncancer pain is a very common reason for consultation with a general practitioner (GP). Recommendations for action and instruments specifically for the GP setting are urgently needed. An upgrade of the guideline to S2 or S3 level and practical aids for joint decision-making for individual long-term patient support should be developed in the future. [ABSTRACT FROM AUTHOR]

The diagnosis of common bile duct (CBD) stones is conducted through various imaging tests, endoscopic examinations, and the patient's clinical presentation. In patients with symptomatic gallstone disease, initial tests such as liver function tests, abdominal ultrasound, and abdominal computed tomography can be performed. Based on the results of these initial tests, symptomatic patient with cholelithiasis can be classified into low risk, intermediate risk, and high risk groups. Low risk of choledocholithiasis is characterized by normal liver function test results and absence of CBD dilation on abdominal ultrasound. For patients in this category, additional tests are not necessary unless symptoms indicating CBD stones persist. Intermediate risk of choledocholithiasis is identified by abnormal liver function test results or CBD dilation on abdominal ultrasound. Additional tests such as endoscopic ultrasound or magnetic resonance cholangiopancreatography can be performed. If CBD stones are confirmed in the additional tests, endoscopic retrograde cholangiopancreatography (ERCP) is required. High risk of choledocholithiasis is diagnosed when there is clinical evidence of cholangitis or CBD stones are identified on imaging tests. In such cases, ERCP is recommended for both diagnosis and treatment purposes without the need for further additional tests. [ABSTRACT FROM AUTHOR]

Common bile duct (CBD) stones carry a risk of complications including biliary obstruction, acute cholangitis and pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) is regarded as the standard of treatment for CBD stones nowadays. However, ERCP can cause severe adverse events such as bleeding, post-ERCP pancreatitis and perforation. Therefore, it is important to provide practical guideline to manage CBD stones for clinicians. The Korean Pancreatobiliary Association (KPBA) established the first Korean guidelines for the management of CBD stones in 2013. Taking together the recently developed techniques for CBD stones and evidence newly obtained, the committee of the KPBA decided to perform an extensive revision of the guidelines. These revised guidelines were developed based on consensusbased guideline using Delphi methods. The main topics of these guidelines fall under the following topics: 1) diagnosis, 2) endoscopic management, 3) endoscopic management for difficult CBD stones. The specific recommendations are presented with the quality of evidence and classification of recommendations. [ABSTRACT FROM AUTHOR]

Objective(s): Pediatric epistaxis is a common, often non‐operative condition encountered by Otolaryngologists. The present study seeks to (1) describe our outcomes of epistaxis management, (2) estimate the associated healthcare burden, and (3) propose a clinical model to optimize care coordination with primary care and advanced practice providers. Methods: Retrospective case series of pediatric patients treated outpatient for epistaxis by a single otolaryngologist from 2021 to 2022. The primary outcome after treatment with nasal lubricants was defined as (1) refractory epistaxis, (2) improvement, or (3) complete resolution. Cost data for office versus operative nasal cautery were analyzed. Results: In total, 122 patients were included for analysis. Over a follow‐up duration of 20.5 months (IQR 8–36), 24.6% of patients experienced refractory epistaxis, 41.8% of patients found improvement, and 33.6% had complete resolution (n = 122). Refractory epistaxis was associated with a family history of coagulopathy (p =.007), daily epistaxis episodes (p =.043), and anemia (p <.001). Average direct hospital costs associated with nasal cautery were $187 for in‐office cauterization and $2179 for intraoperative cauterization. Estimated patient/third party payors savings were $1617 and $15,412 for in‐office and intraoperative procedures, respectively, and $541.59 for specialty office visits alone. The average charge for laboratory work‐up was $576. Conclusion: Approximately 75% of patients with epistaxis experienced improvement or resolution of symptoms with nasal lubrication alone. Refractory epistaxis was associated with a family history of coagulopathy, daily epistaxis episodes, and anemia. Otolaryngology visits for epistaxis were associated with a direct healthcare expense burden. Adaptation of our clinical model may mitigate these costs while improving patient care. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

This document is a guideline on endoscopic surgery for qualified surgeons, specifically focusing on the pancreas. It provides a historical overview of laparoscopic pancreatectomy and discusses the insurance coverage for this procedure in Japan. The document also evaluates the use of laparoscopic distal pancreatectomy (LDP) and laparoscopic pancreatoduodenectomy (LPD) for pancreatic tumors, comparing them to open surgery. The guideline recommends LDP for benign or low-grade lesions and LPD for benign and low-grade tumors in facilities with experience in this surgery. However, further research is needed, particularly for LPD in pancreatic cancer. [Extracted from the article]

This article provides practice guidelines for qualified surgeons on the use of laparoscopic surgery for various conditions related to colorectal cancer. The guidelines recommend laparoscopic surgery for colon cancer due to its comparable long-term results and superior short-term outcomes compared to open surgery. However, the use of laparoscopic surgery for transverse colon and rectal cancer is still controversial. The guidelines also discuss the applicability of laparoscopic surgery based on disease stage, comorbidities, and age. Overall, laparoscopic surgery is considered safe and effective, but individual patient factors should be carefully considered. The article also mentions the use of laparoscopic surgery for acute appendicitis, diverticula of the large intestine, ulcerative colitis, Crohn's disease, elderly patients, obese patients, and Stage IV colorectal cancer, providing insights into the short-term and long-term outcomes of laparoscopic surgery for these conditions. The article concludes that further research is needed, particularly in the area of robotic surgery for colorectal cancer. [Extracted from the article]

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this article, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. [ABSTRACT FROM AUTHOR]

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. [ABSTRACT FROM AUTHOR]

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this guideline, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. [ABSTRACT FROM AUTHOR]

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute diverticulitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. [ABSTRACT FROM AUTHOR]

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intraabdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this article, the panel provides recommendations for diagnostic imaging of suspected acute cholecystitis and acute cholangitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. [ABSTRACT FROM AUTHOR]

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America (IDSA). In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. [ABSTRACT FROM AUTHOR]

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides a recommendation for risk stratification according to severity of illness score. The panel's recommendation is based on evidence derived from systematic literature reviews and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. [ABSTRACT FROM AUTHOR]

As the first part of an update to the clinical practice guideline on the diagnosis and management of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, the panel presents 21 updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. [ABSTRACT FROM AUTHOR]

A substantial portion of patients with advanced cancer cannot be cured, regardless of the therapeutic methods employed. Hence, rational palliative causal treatment becomes crucial. Representative studies specifically addressing the exclusive palliative treatment of patients diagnosed with tracheal cancers have not been identified. In most studies, patients treated palliatively constituted a subset of the overall evaluated group. A thorough literature review was conducted, focusing on three types of palliative treatment: palliative radiotherapy, palliative surgical procedures, and systemic treatment for advanced disease. This review uniquely fills a significant gap in the existing literature by providing the first comprehensive and updated clinical practice guidelines specifically focused on the palliative treatment of tracheal tumors. The proposed guidelines emphasize the unique clinical challenges and treatment strategies pertinent to palliative care in tracheal tumors, which are not adequately covered in existing guidelines for other thoracic malignancies. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection, which mostly causes a subclinical infection early in life, has important clinical consequences in certain patient groups. CMV is the most common congenital infection and can cause permanent disabilities such as hearing loss and motor- and cognitive deficits in affected infants. In allogeneic haematopoietic stem cell and solid organ transplant recipients, CMV still is an important infectious complication with a risk for life-threatening disease. The previous Swedish recommendations for the management of CMV infections were updated by an expert group under the guidance of The Swedish Reference Group for Antiviral Treatment (RAV) and published at the website of RAV in August 2023 (). We here provide a translation of the updated recommendations, with minor modifications regarding diagnosis of CMV pneumonia. In the present recommendations, we discuss aspects of old and new CMV antivirals, including dosing for different age groups, and cover the management of congenital infections and CMV in immunocompromised patients. The recommendations are evidence-graded in accordance with the Oxford Centre for Evidence-Based Medicine. [ABSTRACT FROM AUTHOR]

Background: The selection of statistical analysis methods in research is a critical and nuanced task that requires a scientific and rational approach. Aligning the chosen method with the specifics of the research design and hypothesis is paramount, as it can significantly impact the reliability and quality of the research outcomes. Methods: This study explores a comprehensive guideline for systematically choosing appropriate statistical analysis methods, with a particular focus on the statistical hypothesis testing stage and categorization of variables. By providing a detailed examination of these aspects, this study aims to provide researchers with a solid foundation for informed methodological decision making. Moving beyond theoretical considerations, this study delves into the practical realm by examining the null and alternative hypotheses tailored to specific statistical methods of analysis. The dynamic relationship between these hypotheses and statistical methods is thoroughly explored, and a carefully crafted flowchart for selecting the statistical analysis method is proposed. Results: Based on the flowchart, we examined whether exemplary research papers appropriately used statistical methods that align with the variables chosen and hypotheses built for the research. This iterative process ensures the adaptability and relevance of this flowchart across diverse research contexts, contributing to both theoretical insights and tangible tools for methodological decision-making. Conclusions: This study emphasizes the importance of a scientific and rational approach for the selection of statistical analysis methods. By providing comprehensive guidelines, insights into the null and alternative hypotheses, and a practical flowchart, this study aims to empower researchers and enhance the overall quality and reliability of scientific studies. [ABSTRACT FROM AUTHOR]

Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability. [ABSTRACT FROM AUTHOR]

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations. [ABSTRACT FROM AUTHOR]

Purpose: Clinical registries have great potential for quality control of medical procedures regarding the indications, therapeutic processes and results, including their possible complications. This is particularly true when providing patients with severe hearing loss or deafness with a cochlear implant (CI). This treatment represents a lifelong care process that requires continuous quality control over time. On the initiative of the Executive Committee of the German Society of Otorhinolaryngology (Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V., DGHNO-KHC), a national German CI registry (Deutsches Cochlear Implant Register, DCIR) was established in January 2022. This article focuses on the first demographic and baseline data of the DCIR. Methods: The DCIR covers the complete therapeutic process from indication, surgery, fitting and lifelong aftercare in CI therapy. By the end of 2022, 75 hospitals in Germany had agreed to contribute to the DCIR. Results: During the year 2022, 63 hospitals actively contributed data to the DCIR. Pseudonymized data from 2,292 CI implantations (2,176 primary implantations, 99 explantations with immediate re-implantations and 17 re-implantations following an earlier explantation) in 2,108 patients were documented. Cochlear implantation was accomplished in 1,807 adults (≥ 18 years) and 301 children (< 18 years). Fourty patients (1,9%) were children < 1 year of age and 55 (2,6%) were patients > 85 years. From the total of 2,292 implantations, 226 (9.9%) were performed as simultaneous bilateral implantations (CI implantation in both ears of 113 patients on the same day of surgery) and 412 implantations (19.1% of 2,162 implantations with data provided on the contralateral ear's hearing status) were in patients with single sided deafness (normal hearing in the contralateral ear). In addition, the reported complications in 2022 were also evaluated. Seven reports (0.4%) of mild to moderate severe facial nerve dysfunctions were documented. No reports of severe or total facial nerve dysfunction (House-Brackmann grade V/VI), meningitis or death related to CI therapy were documented. Conclusion: Although still in the start-up phase, these initial DCIR data already provide an interesting first insight into the demographic structure and baseline data of CI therapy in Germany. The successful implementation of the DCIR represents an important step towards continuous quality control of CI care. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a bundle to increase safety of intra-hospital transport in critically ill patients. A qualitative design with Delphi approach was conducted for creation of an intra-hospital transport bundle in 3 steps. First, doctors and nurses were questioned about their encounters with intra-hospital transport incidents. Second, several databases were looked through to find published checklists and recommendations for intra-hospital transport. Third, using this strategy, a bundle was created and reviewed with subject matter experts. The content validity index (CVI), which assesses the degree of expert agreement, was utilized to evaluate each item in the generated bundle. Two evaluation cycles were required before a minimal index could be reached. We looked at the content validity and important weighting of the items. The scale-CVI was calculated using the average of all the elements, and it was 1. The created bundle serves as a framework for directing doctors and nurses during intra-hospital transportation and offers continuity of care to improve patient safety. The techniques suggested in this study can be used to adapt this bundle to the needs of other hospitals. [ABSTRACT FROM AUTHOR]

Background: The objectives of this work were as follows: (1) to develop holistic recommendations for physical activity, sleep, sedentary behaviours and eating habits adapted to children and adolescent life stage (5–17 years) and targeting optimal metabolic cycle and achieving energy balance; (2) to provide evidence-based information that can be used by the government, policy makers, healthcare professionals, community, schools as well as families to endorse active, healthy, living in apparently healthy children and youth aged 5–17 years, and as a base for monitoring the activities, particularly the physical ones, on the people level. The Egyptian Academy of Bone and Muscle Health followed an established guideline development process to create the Egyptian 24-h movement clinical guideline for children and adolescents. Online databases (PubMed, Embase and Cochrane Library) were searched for relevant peer-reviewed studies that met the a priori inclusion criteria. Results: A total of 41 studies met the inclusion criteria. Leveraging evidence from the review of the literature led to the development of 11 key questions covering 8 domains. Fifteen statements focus on the overall identified targets through integration of the movement activities and eating behaviour. Results revealed a major change in the previous basic understandings as it shifts away from segregated into integrated movement behaviour and dietary habit paradigm. Based on this, the final guideline was developed providing evidence-based recommendations for a "Healthy 24-h day", for Egyptian children and adolescents. Conclusion: The 24-h composition of movement behaviours has principal implications for health at all ages. The developed guideline provides an up-to-date evidence-based recommendation towards a holistic approach for favourable daily life activities and adopts a feasible perspective by outlining these activities within a 24-h period. In addition, eating and dietary elements have been included to complete the energy cycle. Children and adolescents who meet the 24-h movement guidelines generally report more favourable health indicators than those who do not. [ABSTRACT FROM AUTHOR]

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More than 80% of newborn infants experience jaundice as a result of elevated bilirubin during the first few weeks after birth. In most cases, hyperbilirubinemia is physiologic, but persistent and extreme elevations can lead to serious long-term complications, such as kernicterus. To avoid these complications and help clinicians in the successful assessment, evaluation, and treatment of hyperbilirubinemia, the American Academy of Pediatrics updated its clinical practice guideline for neonatal hyperbilirubinemia. This article reviews the guideline and highlights significant updates, such as an elevation in the threshold for phototherapy and exchange transfusion, inclusion of gestational age, and removal of racially based norms. [ABSTRACT FROM AUTHOR]

Cancer is a heterogeneous and multifaceted disease with a significant global footprint. Despite substantial technological advancements for battling cancer, early diagnosis and selection of effective treatment remains a challenge. With the convenience of large-scale datasets including multiple levels of data, new bioinformatic tools are needed to transform this wealth of information into clinically useful decision-support tools. In this field, artificial intelligence (AI) technologies with their highly diverse applications are rapidly gaining ground. Machine learning methods, such as Bayesian networks, support vector machines, decision trees, random forests, gradient boosting, and K-nearest neighbors, including neural network models like deep learning, have proven valuable in predictive, prognostic, and diagnostic studies. Researchers have recently employed large language models to tackle new dimensions of problems. However, leveraging the opportunity to utilize AI in clinical settings will require surpassing significant obstacles—a major issue is the lack of use of the available reporting guidelines obstructing the reproducibility of published studies. In this review, we discuss the applications of AI methods and explore their benefits and limitations. We summarize the available guidelines for AI in healthcare and highlight the potential role and impact of AI models on future directions in cancer research. [ABSTRACT FROM AUTHOR]

Oncobiosis has emerged as a key contributor to the development, and modulator of the treatment efficacy of cancer. Hereby, we review the modalities through which the oncobiome can support the progression of tumors, and the emerging therapeutic opportunities they present. The review highlights the inherent challenges and limitations faced in sampling and accurately characterizing oncobiome. Additionally, the review underscores the critical need for the standardization of microbial analysis techniques and the consistent reporting of microbiome data. We provide a suggested metadata set that should accompany microbiome datasets from oncological settings so that studies remain comparable and decipherable. [ABSTRACT FROM AUTHOR]

Background: High-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data. Methods: The retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time. Results: The sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p <.001), receiving predominantly strong opioids (OR = 6.79, p <.001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p <.001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time. Conclusions: The results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal. Trial registration: German Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021. [ABSTRACT FROM AUTHOR]