Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study.

BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

Consensus guidelines for the diagnosis and management of isolated sulfite oxidase deficiency and molybdenum cofactor deficiencies.

Sulfite intoxication is the hallmark of four ultrarare disorders that are caused by impaired sulfite oxidase activity due to genetic defects in the synthesis of the molybdenum cofactor or of the apoenzyme sulfite oxidase. Delays on the diagnosis of these disorders are common and have been caused by their unspecific presentation of acute neonatal encephalopathy with high early mortality, followed by the evolution of dystonic cerebral palsy and also by the lack of easily available and reliable diagnostic tests. There is significant variation in survival and in the quality of symptomatic management of affected children. One of the four disorders, molybdenum cofactor deficiency type A (MoCD-A) has recently become amenable to causal treatment with synthetic cPMP (fosdenopterin). The evidence base for the rational use of cPMP is very limited. This prompted the formulation of these clinical guidelines to facilitate diagnosis and support the management of patients. The guidelines were developed by experts in diagnosis and treatment of sulfite intoxication disorders. It reflects expert consensus opinion and evidence from a systematic literature search.

Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials.

INTRODUCTION: Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation of a common data model would further enhance biomarker discovery by enabling effective concatenation of data from multiple studies. METHODS: The Response Evaluation in Neurofibromatosis and Schwannomatosis biomarker working group reviewed published data on emerging trends in neurofibromatosis 1 and schwannomatosis biomarker research and developed recommendations in a series of consensus meetings. RESULTS: Liquid biopsy has emerged as a promising assay for neurofibromatosis 1/schwannomatosis biomarker discovery and validation. In addition, we review recommendations for a range of biomarkers in clinical trials, neurofibromatosis 1/schwannomatosis-specific data annotations, and common data models for data integration. CONCLUSION: These Response Evaluation in Neurofibromatosis and Schwannomatosis consensus guidelines are intended to provide best practices for the inclusion of biomarker studies in neurofibromatosis 1/schwannomatosis clinical trials, data, and sample annotation and to lay a framework for data harmonization and concatenation between trials.

French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN) guidelines for the management of patients with partially responsive depression and treatment-resistant depression: Update 2024.

INTRODUCTION: The purpose of this update is to add newly approved nomenclatures and treatments as well as treatments yet to be approved in major depressive disorder, thus expanding the discussions on the integration of resistance factors into the clinical approach. METHODS: Unlike the first consensus guidelines based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed an update of these guidelines for the management of partially responsive depression (PRD) and treatment-resistant depression (TRD). The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for PRD and TRD. RESULTS: The recommendations addressed three areas judged as essential for updating the previous 2019 AFPBN guidelines for the management of patients with TRD: (1) the identification of risk factors associated with TRD, (2) the therapeutic management of patients with PRD and TRD, and (3) the indications, the modalities of use and the monitoring of recent glutamate receptor modulating agents (esketamine and ketamine). CONCLUSION: These consensus-based guidelines make it possible to build bridges between the available empirical literature and clinical practice, with a highlight on the 'real world' of the clinical practice, supported by a pragmatic approach centred on the experience of specialised prescribers in TRD.

Consensus guidelines, Delphi methods, and evidence around anaesthetic technique for endoscopic retrograde cholangiopancreatography.

Consensus guidelines on the anaesthetic management of endoscopic retrograde cholangiopancreatography (ERCP) have recently been published. The rigorous synthesis of expert opinion is invaluable when there are limited data, and these guidelines are a significant step forward. This review both guides practice and identifies important research questions. We challenge those working in this field to collaborate and produce the evidence for whether monitored anaesthesia care (MAC) is associated with a lower incidence of adverse events and better outcomes than general anaesthesia for ERCP.

Taiwanese dermatological association (TDA) consensus for the management of pemphigus.

Pemphigus is an uncommon but life-threatening autoimmune blistering disease characterized by the presence of antibodies against desmogleins. Without effective treatment, pemphigus can result in significant morbidity and mortality. Existing consensus statements on pemphigus management from international medical groups provide varying guidelines, especially on treatment. Thus, on January 4, 2020, a panel of seven dermatology experts from the Taiwanese Dermatological Association (TDA) and one rheumatology expert convened to develop a consensus for the management of pemphigus. These experts with extensive experience in pemphigus management were recommended by their respective teaching hospitals and primary care clinics in Taiwan and by the TDA. The meeting reviewed the available consensus statements from international dermatology groups, including the European Dermatology Forum (EDF), the European Academy of Dermatology and Venereology (EADV), and the International Bullous Diseases Consensus Group. Using these guidelines as a basis for discussion and consensus formulation, these experts formulated their consensus statement that provides practical, concise but comprehensive recommendations as to the diagnosis, treatment, and monitoring of pemphigus patients in Taiwan. This consensus serves as a clinical reference for physicians for the management of pemphigus in Taiwan or wherever it may be applicable.

Pancreatic Cystic Lesions: Review of the Current State of Diagnosis and Surveillance.

Pancreatic cystic lesions (PCLs) are both common and often incidental. These encompass a range of pathologies with varying degrees of concern for malignancy. Although establishing a diagnosis is helpful for determining malignant potential, many PCLs are either too small to characterize or demonstrate nonspecific morphologic features. The most salient modalities involved in diagnosis and surveillance are magnetic resonance imaging, multidetector computerized tomography, and endoscopic ultrasound. Fine needle aspiration has a role in conjunction with molecular markers as a diagnostic tool, particularly for identifying malignant lesions. Although several major consensus guidelines exist internationally, there remains uncertainty in establishing the strength of the association between all PCLs and pancreatic adenocarcinoma, and in showing a benefit from extended periods of imaging surveillance. No consensus exists between the major guidelines, particularly regarding surveillance duration, frequency, or endpoints. This review paper discusses PCL subtypes, diagnosis, and compares the major consensus guidelines with considerations for local adaptability along with questions regarding current and future priorities for research.

Update of evidence- and consensus-based guidelines for the treatment of juvenile idiopathic arthritis (JIA) by the German Society of Pediatric and Juvenile Rheumatic Diseases (GKJR): New perspectives on interdisciplinary care.

BACKGROUND: New therapeutic strategies for juvenile idiopathic arthritis (JIA) have evolved within the past ten years, and as a result, an update of the 2011 recommendations of the German management guidelines was initiated. METHODS: A systemic literature review was performed, overarching principles were proposed and pre-selected via an online survey followed by two multidisciplinary consensus conferences. Pharmacological and non-pharmacological treatments were discussed, statements were proposed and ultimately agreed upon by nominal group technique (NGT). RESULTS: 12 overarching therapeutic principles, as well as 9 recommendations on pharmacological and 5 on non-pharmacological treatments for JIA were agreed upon. CONCLUSION: This report summarizes the recent update of the interdisciplinary, consensus-based German guidelines on the management of JIA. The multi- and interdisciplinary participation of all caregivers was central for this patient-focused update. With these guidelines, physicians can choose an evidence-based approach, which allows better tailored treatment in this vulnerable cohort of children and adolescents.

Incidental Adrenal Masses: Adherence to Guidelines and Methods to Improve Initial Follow-Up: A Systematic Review.

OBJECTIVE: Incidental adrenal masses (IAMs) are detected in approximately 1%-2% of abdominal computed tomography (CT) scans. Recent estimates suggest that more than 70-million relevant CT scans are performed annually in the United States; thus, IAMs represent a significant clinical entity. Most clinical guidelines recommend an initial follow-up evaluation that includes imaging and biochemical testing after index IAM detection. METHODS: Systematic review of literature in the PubMed, EMBASE and Web of Science databases to determine whether guidelines regarding IAM evaluation are followed and to identify effective management strategies. Our initial search was in January 2018 and updated in November, 2019. RESULTS: 31 studies met inclusion criteria. In most institutions, only a minority of patients with IAMs undergo initial follow-up imaging (median 34%, IQR 20%-50%) or biochemical testing (median 18%, IQR 15%-28%). 2 interventions shown to improve IAM evaluation are IAM-specific recommendations in radiology reports and dedicated multi-disciplinary teams. Interventions focused solely on alerting the ordering clinician or primary care provider to the presence of an IAM have not demonstrated effectiveness. Patients who are referred to an endocrinologist are more likely to have a complete IAM evaluation, but few are referred. DISCUSSION: Most patients with an IAM do not have an initial evaluation. The radiology report has been identified as a key component in determining whether IAMs are evaluated appropriately. Care teams dedicated to management of incidental radiographic findings also improve IAM follow-up. Although the evidence base is sparse, these interventions may be a starting point for further inquiry into optimizing care in this common clinical scenario.

Challenges and opportunities in the establishment of a hereditary breast cancer clinic at an academic medical center in a low-middle income country.

It is now standard of care to offer genetic testing to patients at risk of hereditary breast cancer and make management decisions based on these results. Although great strides have been made in ensuring access to genetic testing and genetic counseling by establishing hereditary breast cancer clinics in well-resourced countries, these are essentially non-existent in low-middle income countries like Pakistan. We established a hereditary breast cancer clinic involving a multidisciplinary team, including a medical geneticist and a genetic counselor. Our efforts were based on consensus guidelines and included educating medical providers about the importance of genetic testing in breast cancer care and the mandatory presence of a genetics team member at the weekly Breast Tumor Board meeting. This resulted in an increase in the number of referrals of breast cancer patients for genetic testing. In this report, we describe the challenges we faced in setting up such a system in Pakistan and the measures to overcome them. There is a need to establish such hereditary breast cancer clinics, which can also be replicated at other centers in low-resource settings, to improve standardized assessment and management of the patients with hereditary breast cancer according to consensus guidelines.

Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan.

BACKGROUND: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. METHODS: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. RESULTS: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. CONCLUSIONS: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency.

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided.

Patient-centered Opioid Prescribing: Breaking Away From One-Size-Fits-All Prescribing Guidelines.

BACKGROUND: Procedure-based opioid-prescribing guidelines have reduced the amount of opioids prescribed after surgery; however, many patients are still overprescribed opioids. The 24-h predischarge opioid consumption (PDOC) metric has been proposed to guide patient-centered prescribing. MATERIALS AND METHODS: This is a single-institution, retrospective study of patients who underwent major abdominal surgery. We assessed the correlation between inpatient opioid use and discharge prescriptions using morphine milligram equivalents (MMEs). The adequacy of discharge prescriptions for individual patients was assessed using 2 models, one assuming constant opioid use (based on 24-h PDOC) and the other assuming a linear taper. RESULTS: Of 596 included patients, gastric bypass and colectomy were the most common operations. Median length of stay was 3.5 d. Inpatient opioid use and discharge prescriptions were weakly correlated (r = 0.35). Patients with no opioid use 24 h before discharge (n = 133, 22.3%) were frequently discharged with opioid prescriptions. Patients with high opioid use (24-h PDOC >60 MME) were often discharged with prescriptions that would have lasted <48 h (164/200, 82%). Assuming constant opioid use, discharge prescriptions would have lasted patients a median of 5.1 d. With linear opioid tapering, 440 (72.9%) patients would have had leftover pills. A theoretical discharge prescription of 4 times 24-h PDOC would reduce the median prescription by 130 MMEs and allow a linear taper for 97.6% of patients. CONCLUSIONS: At our institution, opioid prescribing was rarely patient-centered, with little correlation between patient's inpatient opioid use and discharge prescriptions. This leads to overprescribing for most patients and underprescribing for others.

Prioritizing cervical cancer screening services during the COVID-19 pandemic: Response of an academic medical center and a public safety net hospital in California.

The expeditious diagnosis and treatment of high-grade cervical precancers are fundamental to cervical cancer prevention. However, during the COVID-19 pandemic healthcare systems have at times restricted in-person visits to those deemed urgent. Professional societies provided some guidance to clinicians regarding ways in which traditional cervical cancer screening might be modified, but many gaps remained. To address these gaps, leaders of screening programs at an academic medical center and an urban safety net hospital in California formed a rapid-action committee to provide guidance to its practitioners. Patients were divided into 6 categories corresponding to various stages in the screening process and ranked by risk of underlying high-grade cervical precancer and cancer. Tiers corresponding to the intensity of the local pandemic were constructed, and clinical delays were lengthened for the lowest-risk patients as tiers escalated. The final product was a management grid designed to escalate and de-escalate with changes in the local epidemiology of the COVID-19 pandemic. While this effort resulted in substantial delays in clinical screening services as mandated by the healthcare systems, the population effects of delaying on both cervical cancer outcomes as well as the beneficial effects related to decreasing transmission of severe acute respiratory coronavirus 2 have yet to be elucidated.

The changing paradigm of an aesthetic practice during the COVID-19 pandemic: An expert consensus.

Until vaccination for the SARS-CoV-2 becomes a reality, it appears that the infection is here to stay. With many countries lifting lockdown restrictions, aesthetic clinics have started reopening with strict standard operating procedures in place. It is pertinent that the physician today understands the infection, disinfection measures, and personal protective equipment to reduce chances of viral transmission and provide safe clinical settings for oneself, the staff and the patients. An online meeting of eight experts in the field of aesthetic dermatology was convened, which particularly focussed on PPE in detail, risk categorization of aesthetic procedures, preprocedure recommendations, and generalized and specialized SOP's for aesthetic procedures. These recommendations were aimed to bridge the gap between published guidelines and clinical practice and are by no means fully conclusive, but signify learnings over the past few months in an active clinical aesthetic practice.

Consensus guidelines for the diagnosis and management of invasive candidiasis in haematology, oncology and intensive care settings, 2021.

Patients with haematological malignancies, haemopoietic stem cell transplant recipients and patients requiring admission to intensive care settings are at high risk for invasive candidiasis (IC). Over the past decade, there has been increased reporting of non-albicans species and fluconazole resistance in Australia. These guidelines provide updated evidence-based recommendations for the diagnosis and management of IC in adult and paediatric haematology, oncology and intensive care settings. Optimal pharmacological and non-pharmacological management are discussed. Recent studies strengthen the recommendation for an echinocandin agent as first-line therapy for high-risk patients with IC. Mortality benefit has also been demonstrated for non-pharmacological management, including removal of central venous catheters, infectious diseases consultation and use of care bundles. Healthcare facilities managing immunocompromised patient populations should therefore adopt implementation strategies for these multimodal interventions.

THE PROCESS OF DEVELOPING CONSENSUS GUIDELINES BY DENTAL ONCOLOGISTS FOR PRE-RADIOTHERAPY DENTAL CARE IN HEAD AND NECK CANCER PATIENTS USING THE MODIFIED DELPHI TECHNIQUE.

BACKGROUND: There is a range of pre-radiation therapy (RT) dental care strategies used to prevent the side effects associated with the use of RT in the treatment of head and neck cancer. However, there is a paucity of evidence-based, prospectively tested clinical practice guidelines for dentists to utilize in the provision of care prior to RT. PURPOSE: The aim of this study is to describe the process of creating consensus guidelines for dental care in head and neck cancer patients undergoing RT using the Modified Delphi Technique. PROCEDURE: We invited 44 dental oncologists to participate as panelists in the study. Three rounds of iterative structured surveys were completed within eight months, followed by a virtual meeting to conclude the modified Delphi process. Questions were divided into six main domains and patients were categorized as low, moderate, and high-risk based on factors identified by panelists and agreed upon during the first round. The threshold value set for each round of the Delphi process was a 70% response rate and 75% Consensus level. FINDINGS: Eighteen panelists out of the forty-four (41% overall response rate) completed the study. The number of questions that achieved the set consensus level in rounds 1,2,3 and the virtual meeting were 24%, 62%,61% and 81%, respectively. A confidence level of 95% and a response rate of >75% were reached throughout the process. CONCLUSION: Consensus was attained in most of the questions in all domains, which will be utilized to develop guidelines for dental care in head and neck cancer patients before the commencement of RT.

Therapeutic Monitoring of Vancomycin for Serious Methicillin-resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400-600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.

COVID-19 Pandemic: Consensus guidelines for preferred practices in an aesthetic clinic.

Strict infection control measures in response to the current COVID-19 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS-CoV-2 infection. Consensus guidelines for "preferred practices" were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low-risk, moderate risk, and high-risk based on the likelihood of transmission of SARS-CoV-2 virus from the patient to the treating physician or therapist. While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID-19 infection in aesthetic clinics.