Medicine Clinical Practice Guideline Research Articles

Choice of resuscitation fluids in critically ill adults: key messages from the European Society of Intensive Care Medicine 2024 clinical practice guideline.

The 2024 European Society of Intensive Care Medicine clinical practice guideline provide clinicians with evidence-based recommendations on intravenous fluid in critically ill adults across a range of common conditions. These guidelines aim to improve the practices of fluid therapy by adopting a global perspective that considers both clinical efficacy and resource utilization in diverse healthcare settings. The guidelines address three key questions: (1) albumin versus crystalloids, (2) balanced crystalloids versus isotonic saline, and (3) small-volume hypertonic solutions versus isotonic crystalloids. Recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, ensuring a rigorous and transparent evaluation of the evidence across critical outcomes. Albumin was generally not favored over crystalloids due to its lack of demonstrated mortality benefit, higher cost, and limited availability in resource-limited settings. Balanced crystalloids were suggested over isotonic saline in most scenarios due to their potential to reduce mortality and mitigate the harmful effects of hyperchloremia, although the certainty of evidence was low. Small-volume hypertonic solutions were not shown to provide significant advantages over isotonic crystalloids, leading to a preference for the latter based on very low certainty evidence. This review provides an overview of the guideline development process and a detailed summary of their recommendations, highlighting key considerations for clinical practice. The guidelines also identify critical evidence gaps in fluid therapy research, underscoring the need for future studies to refine and optimize fluid management strategies in critically ill patients.

Effectiveness of using implementation frameworks to facilitate the implementation of a stroke management guideline in the traditional Chinese medicine hospitals in China: protocol for a factorial randomised controlled trial

IntroductionTraditional Chinese medicine (TCM) is commonly used alongside Western medicine for stroke management in China. However, there is significant variation in TCM practice, and the utilisation of evidence-based clinical practice...

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline.

This guideline establishes clinical practice recommendations for Treatment of Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD) in adults and pediatric patients. The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RLS. The following recommendations are intended as a guide for clinicians in choosing a specific treatment for RLS and PLMD in adults and children. Each recommendation statement is assigned a strength ("Strong" or "Conditional"). A "Strong" recommendation (i.e., "We recommend…") is one that clinicians should follow under most circumstances. The recommendations listed below are ranked in the order of strength of recommendations and grouped by class of treatments within each PICO question. Some recommendations include remarks that provide additional context to guide clinicians with implementation of this recommendation.

Liberation from Mechanical Ventilation in Critically Ill Patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

Successful liberation from mechanical ventilation is one of the most crucial processes in critical care, because it is the first step through which a respiratory failure patient begins to transition out of the intensive care unit, and return to normal life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider scientific and systematic approaches, as well as the individual experiences of healthcare professionals. Recently, numerous studies have investigated methods and tools to identify when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians for liberation from the ventilator. Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. These evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved the recommendations. Recommendations for nine questions on ventilator liberation about Population, Intervention, Comparator, and Outcome (PICO) are presented in this document. This guideline presents seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

European Society of Intensive Care Medicine clinical practice guideline on fluid therapy in adult critically ill patients. Part 1: the choice of resuscitation fluids.

This is the first of three parts of the clinical practice guideline from the European Society of Intensive Care Medicine (ESICM) on resuscitation fluids in adult critically ill patients. This part addresses fluid choice and the other two will separately address fluid amount and fluid removal. This guideline was formulated by an international panel of clinical experts and methodologists. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was applied to evaluate the certainty of evidence and to move from evidence to decision. For volume expansion, the guideline provides conditional recommendations for using crystalloids rather than albumin in critically ill patients in general (moderate certainty of evidence), in patients with sepsis (moderate certainty of evidence), in patients with acute respiratory failure (very low certainty of evidence) and in patients in the perioperative period and patients at risk for bleeding (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than albumin in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using albumin rather than crystalloids in patients with cirrhosis (very low certainty of evidence). The guideline provides conditional recommendations for using balanced crystalloids rather than isotonic saline in critically ill patients in general (low certainty of evidence), in patients with sepsis (low certainty of evidence) and in patients with kidney injury (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than balanced crystalloids in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using isotonic crystalloids rather than small-volume hypertonic crystalloidsin critically ill patients in general (very low certainty of evidence). This guideline provides eleven recommendations to inform clinicians on resuscitation fluid choice in critically ill patients.

The American Society of Addiction Medicine Clinical Practice Guideline Development Methodology.

The American Society of Addiction Medicine (ASAM) has published clinical practice guidelines (CPGs) since 2015. As ASAM's CPG work continues to develop, it maintains an organizational priority to establish rigorous standards for the trustworthy production of these important documents. In keeping with ASAM's mission to define and promote evidence-based best practices in addiction prevention, treatment, and recovery, ASAM has rigorously updated its CPG methodology to be in line with evolving international standards. The CPG Methodology and Oversight Subcommittee was formed to establish and publish a methodology for the development of ASAM CPGs and to develop an ASAM CPG strategic plan. This article provides a focused overview of the ASAM CPG methodology.

Characteristics and Quality of Traditional Chinese Therapies and Integrative Medicine Clinical Practice Guidelines for Musculoskeletal Disorders Published in Mainland China

Background: Musculoskeletal disorders are prevalent in adults. Traditional Chinese medicine (TCM) and integrative medicine (IM) are commonly used treatments which have clinical practice guidelines (CPGs). This study aimed to determine the characteristics and quality of these CPGs.Methods: CPGs which recommended TCM/IM therapies in musculoskeletal conditions/diseases published in Chinese or English between January 2018 to December 2022 in mainland China were retrieved and analyzed for guideline classification, funding source, conflict of interest, and methodology. Appraisal of Guideline for Research and Evaluation Ⅱ including 6 domains, was applied to assess CPG quality.Results: Of the 50 CPGs included, there were 19 TCM, 5 IM, and 26 western conventional medicine (WCM) guidelines of which osteoporosis (13, 26%), osteoarthritis (11, 22%) and rheumatoid arthritis (6, 12%) were the most frequent diseases. The TCM therapies recommended by the CPGs successively were acupuncture and moxibustion, Chinese patent medicine, and TCM decoction based on syndrome differentiation. Nearly half of the CPGs reported funding source (52%) and conflict of interest (48%). Thirty-six CPGs used the Grading of Recommendations, Assessment, Development, and Evaluations method to present summaries of evidence, the remaining did not report the method. Based on Appraisal of Guideline for Research and Evaluation Ⅱ scores, “clarity of presentation” scored the highest (55%), while “applicability” was the lowest (6%). No CPG was recommended without change, and 23 CPGs were not recommended.Conclusion: The quality of CPGs for musculoskeletal conditions/diseases in China is generally low. Future CPGs should pay more attention to standardized developing procedures.

PEER simplified lipid guideline 2023 update: Prevention and management of cardiovascular disease in primary care.

To update the 2015 clinical practice guideline and provide a simplified approach to lipid management in the prevention of cardiovascular disease (CVD) for primary care. Following the Institute of Medicine's Clinical Practice Guidelines We Can Trust, a multidisciplinary, pan-Canadian guideline panel was formed. This panel was represented by primary care providers, free from conflicts of interest with industry, and included the patient perspective. A separate scientific evidence team performed evidence reviews on statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors, fibrates, bile acid sequestrants, niacin, and omega-3 supplements (docosahexaenoic acid with eicosapentaenoic acid [EPA] or EPA ethyl ester alone [icosapent]), as well as on 11 supplemental questions. Recommendations were finalized by the guideline panel through use of the Grading of Recommendations Assessment, Development and Evaluation methodology. All recommendations are presented in a patient-centred manner designed with the needs of family physicians and other primary care providers in mind. Many recommendations are similar to those published in 2015. Statins remain first-line therapy for both primary and secondary CVD prevention, and the Mediterranean diet and physical activity are recommended to reduce cardiovascular risk (primary and secondary prevention). The guideline panel recommended against using lipoprotein a, apolipoprotein B, or coronary artery calcium levels when assessing cardiovascular risk, and recommended against targeting specific lipid levels. The team also reviewed new evidence pertaining to omega-3 fatty acids (including EPA ethyl ester [icosapent]) and proprotein convertase subtilisin-kexin type 9 inhibitors, and outlined when to engage in informed shared decision making with patients on interventions to lower cardiovascular risk. These updated evidence-based guidelines provide a simplified approach to lipid management for the prevention and management of CVD. These guidelines were created by and for primary health care professionals and their patients.

Clinical Practice Patterns for Benign Prostatic Hyperplasia: An Online Survey

Objectives: This study investigated Korean medicine doctors’ perspectives on clinical practice patterns in the process of developing Korean medicine clinical practice guidelines for benign prostatic hyperplasia.Methods: A questionnaire was developed for Korean medicine doctors. A total of 323 oriental medicine doctors participated in the survey, which was live for a total of 9 days from September 22, 2022, to September 30, 2022.Results: Regarding awareness of treatments for benign prostatic hyperplasia, 63.8% of respondents showed high awareness of Korean medical treatments. However, items such as diagnostic criteria (17.7%), evaluation methods (17.0%), and Western medical treatments (22.9%) showed low recognition rates. In clinical practice, 76.2% of respondents were found to treat five or fewer patients with benign prostatic hyperplasia per month, and the average treatment period was 1 to 3 months for most at 41.2%. Korean medicine doctors diagnosed benign prostatic hyperplasia based on clinical features. The main interventions used were acupuncture, herbal medicine (prescription medicine), and moxibustion. This study has several limitations because of the low response rate for this survey; therefore, the participants are not representative of all Korean medicine doctors. In addition, because the study was conducted broadly on various topics related to benign prostatic hyperplasia, sufficient quality management was not carried out. Further studies that include a larger sample size and more in-depth studies on benign prostatic hyperplasia are needed.Conclusions: It is necessary to develop appropriate and reasonable Korean medicine clinical practice guidelines for benign prostatic hyperplasia.

Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Interpretation of new concepts and approaches in the ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies

Acute respiratory distress syndrome (ARDS) continues to be one of the most life-threatening conditions for patients in the intensive care unit (ICU). The 2023 European Society of Intensive Care Medicine guidelines on ARDS: definition, phenotyping and respiratory support strategies (2023 Guideline) update the 2017 An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: mechanical ventilation in adult patients with ARDS (2017 Guideline), including 7 aspects of 3 topics of definitions, phenotyping, and respiratory support strategies [including high flow nasal cannula oxygen (HFNO), non-invasive ventilation (NIV), neuromuscular blocking agents (NMBA), extracorporeal life support (ECLS), positive end-expiratory pressure (PEEP) with recruitment maneuvers (RM), tidal volume (VT), and prone positioning]. 2023 Guideline review and summarize the literature since the publication of the 2017 Guideline, covering ARDS and acute hypoxemic respiratory failure, as well as ARDS caused by novel coronavirus infection. Based on the most recent medical evidence, the 2023 Guideline provide clinicians with new ideas and approaches for nonpharmacologic respiratory support strategies for adults with ARDS. This article provides interpretation of the new concepts, the new approaches, the new recommended grading and new levels of evidence for ARDS in the 2023 Guideline.

Korean Medicine Clinical Practice Guideline Update for Temporomandibular Disorders: An Evidence-Based Approach.

Many updated clinical research results have been published since the Korean Medicine Clinical Practice Guidelines (KMCPGs) for temporomandibular disorders (TMDs) were published in 2018. Therefore, it is necessary to update the existing clinical practice guidelines (CPGs). This study presents updated recommendations for TMD treatment based on current research data published up to February 2020. The draft version of the level of evidence and grade of recommendation was determined through an assessment of the risk of bias and a meta-analysis of selected literature based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The final guidelines were derived using the Delphi method. Eighteen recommendations were derived for eight items of Korean medicine treatment for TMDs. Compared with previous Korean medicine CPGs for TMDs, the grades of seven recommendations, including acupuncture, pharmacopuncture, and Chuna manual therapy, were increased. The grades of the two recommendations have been changed. Six new recommendations were added to fully reflect clinical reality. Acupuncture, pharmacopuncture, and Chuna manual therapy are recommended for TMD patients in clinical practice. Concurrent conventional conservative therapy with Korean medicine or a combination of Korean medicines should be considered in clinical practice in patients with temporomandibular disorders.

A Rapid Systematic Review of Pharmacologic Sleep Promotion Modalities in the Intensive Care Unit.

Background: The Society of Critical Care Medicine Clinical Practice Guidelines for Management of Pain, Agitation, Delirium, Immobility, and Sleep recommend protocolized non-pharmacologic sleep improvement. Pharmacologic interventions are frequently initiated to promote sleep but the evidence supporting these strategies remains controversial. Purpose: To systematically search and synthesize evidence evaluating pharmacologic sleep promotion modalities in critically ill adults. Methods: A rapid systematic review protocol was used to search Medline, Cochrane Library, and Embase for reports published through October 2022. We included randomized controlled trials (RCTs) and before-and-after cohort studies evaluating pharmacologic modalities intended to improve sleep in adult intensive care unit (ICU) patients. Sleep-related endpoints were the primary outcome of interest. Study and patient characteristics and relevant safety and non-sleep outcome data were also collected. The Cochrane Collaboration Risk of Bias or Risk of Bias in Non-Randomized Studies of Interventions were used to assess the risk of bias for all included studies. Results: Sixteen studies (75% RCTs) enrolling 2573 patients were included; 1207 patients were allocated to the pharmacologic sleep intervention. Most studies utilized dexmedetomidine (7/16; total n = 505 patients) or a melatonin agonist (6/16; total n = 592 patients). Only half of the studies incorporated a sleep promotion protocol as standard of care. Most (11/16, 68.8%) studies demonstrated a significant improvement in ≥1 sleep endpoint (n = 5 dexmedetomidine, n = 3 melatonin agonists, n = 2 propofol/benzodiazepines). Risk of bias was generally low for RCTs and moderate-severe for cohort studies. Conclusions: Dexmedetomidine and melatonin agonists are the most studied pharmacologic sleep promotion modalities, but current evidence does not support their routine administration in the ICU to improve sleep. Future RCTs evaluating pharmacologic modalities for ICU sleep should consider patients' baseline and ICU risks for disrupted sleep, incorporate a non-pharmacologic sleep improvement protocol, and evaluate the effect of these medication interventions on circadian rhythm, physiologic sleep, patient-perceived sleep quality, and delirium.

A Survey on Korean Medicine Doctors’ Recognition for Developing Korean Medicine Clinical Practice Guidelines for Gastric Cancer

Objective: The purpose of this study was to provide data for the development of Korean medicine (KM) clinical practice guidelines (CPG) for gastric cancer (GC) by identifying the awareness and knowledge needs of KM doctors (KMD) through an online survey.Methods: A survey questionnaire was produced by referring to the previous recognition survey studies for clinical KMDs. The survey questionnaire was composed of questions regarding the current status of clinical care for GC, the knowledge level of clinicians about GC, and other details that clinicians use during practice. The survey was conducted from September 20 to October 22, 2021. An online survey was conducted with 195 KMDs from the Society of Korean Medicine and the Korean Association of Traditional Oncology of KM.Results: A total of 195 respondents participated in the online survey regarding the current status of GC treatment. Of this number, 10.3% of the respondents specialize in GC, but even if they do not currently specialize in GC, they are more likely to treat patients with GC in the future. In terms of the specifics of KM treatment, there was a demand for information on comprehensive KM treatment methods, such as herbal medicine, acupuncture, moxibustion, cupping, and chuna, as well as on analyzing the effectiveness of combined treatment with chemotherapy and radiation.Conclusion: In this study, we were able to understand the clinical KMDs’ perception of GC, knowledge level, and requirements in the CPG. The results of this study will provide the basic data for the development of CPG for GC.

National Health Insurance Data Analysis for the Second-Wave Development of Korean Medicine Clinical Practice Guidelines in South Korea

National Health Insurance Data Analysis for the Second-Wave Development of Korean Medicine Clinical Practice Guidelines in South Korea

0573 Application of AASM Clinical Significance Thresholds to Once-Nightly Sodium Oxybate for Improvement in Narcolepsy Symptoms

Abstract Introduction Once-nightly sodium oxybate (ON-SXB; FT218), an investigational, extended-release treatment, was evaluated for the treatment of narcolepsy in adults in the phase 3 REST-ON clinical trial (NCT02720744). The 3 co-primary endpoints, mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement rating, and weekly number of cataplexy attacks (NCA), and the secondary endpoint of Epworth Sleepiness Scale (ESS) score were significant for ON-SXB vs placebo at weeks 3 (6-g dose), 8 (7.5-g dose), and 13 (9-g dose; all P< 0.001). These data were published after the cutoff for inclusion in the American Academy of Sleep Medicine (AASM) clinical practice guidelines for narcolepsy treatment; thus, REST-ON results were analyzed according to AASM clinical significance thresholds (CSTs). Methods Individuals with narcolepsy type 1/2 and age ≥16 years were randomized 1:1 to receive double-blind ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or matching placebo. For each dose (6 g, week 3; 7.5 g, week 8; and 9 g, week 13), least-squares mean (LSM) difference from placebo was calculated for change from baseline in mean sleep latency on the MWT, ESS score, and percentage reduction in NCA. As defined in the 2021 AASM guidelines, CSTs were the following changes vs placebo: MWT, ≥2-minute increase; ESS, ≥2-point decrease; and cataplexy, ≥25% decrease in NCA. Results 190 participants (ON-SXB, n=97; placebo, n=93) were in the modified intent-to-treat population. On the MWT, difference in LSM change from baseline was 5.0, 6.2, and 6.1 minutes for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM change from baseline ESS scores were −2.1, −3.2, and −3.9 for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM percentage reduction in NCA were 26.0%, 34.2%, and 36.1% for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Conclusion Clinically significant improvement in excessive daytime sleepiness and cataplexy per AASM-established criteria was met with ON-SXB 6, 7.5, and 9 g doses. If FDA approved, ON-SXB will provide a once-nightly treatment for improving EDS and cataplexy in adults with narcolepsy. Support (if any) Avadel Pharmaceuticals

0260 Establishment of a polysomnography databank for sleep disorders in Japan

Abstract Introduction Polysomnography (PSG) has been suggested to be useful as an objective indicator (biomarker) that contributes to the diagnosis and severity evaluation of various sleep disorders. However, its regular use is still limited to the specialized institutions for sleep disorders. Therefore, PSG is essential for clinical diagnosis of only some sleep disorders, and further application of PSG in conjunction with biomarker development of disorders including such as insomnia, and psychiatric disorders with comorbid sleep disorders is expected. The aim of this project is to establish a PSG databank for sleep disorders in collaboration with major PSG laboratories in Japan. Methods This project is collaborated with medical and research institutions that conduct PSG on a large scale in Japan. The National Center of Neurology and Psychiatry (NCNP) serves as the core institution. The initial collaborating institution is the Tokyo Medical University, which is in cooperation with the Yoyogi Sleep Disorder Center, the largest PSG facility in the Kanto region. We also collaborate with three other core PSG facilities in the Kanto, Tohoku and Kyushu regions: the Nihon University, the Akita University (in cooperation with the Akita Sleep Clinic), and the Kurume University. This project has been approved by the Ethics Committee of the NCNP. Results We have stored about 3,000 PSG data evaluated by the standard of the American Academy of Sleep Medicine clinical practice guideline or the traditional Rechtschaffen & Kales standard with adjunct clinical metadata for the past 9 years at the NCNP, about 17,900 at the Tokyo Medical University, about 1,900 at the Nihon University, about 500 at the Akita University, and about 3,000 at the Kurume University. We are continuously collecting and banking data for enhancing research availability of the PSG databank for sleep disorders. Conclusion The collected data will be used for research on the development of objective indices for sleep disorders or neuropsychiatric disorders, for which objective indices are lacking in diagnosis and pathological evaluation. Support (if any) This work was supported by the Intramural Research Grant (#2-1) for Neurological and Psychiatric Disorders of NCNP.

Sequencing and combination of current small-molecule inhibitors for chronic lymphocytic leukemia: Where is the evidence?

Small-molecule inhibitors have revolutionized the treatment of chronic lymphocytic leukemia (CLL), a landscape once dominated by chemoimmunotherapy (i.e., an anti-CD20 monoclonal antibody in combination with systemic chemotherapy) in fit and unfit individuals. Key challenges include the management of refractory disease as well as the optimization of the therapy sequence. Decreased responsiveness has been observed with prolonged treatment, especially with Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) inhibitors which are given continuously, while venetoclax, an agent that targets dysregulations in intrinsic apoptosis signaling, has a fixed duration when combined with anti-CD20 monoclonal antibodies or BTK inhibitors. Combination therapy aims to synergistically target different oncogenic signaling pathways to abrogate the proliferation of resistant clones and thereby allows for fixed-duration treatments. An advantage of fixed-duration therapy is the potential to decrease financial and drug-induced toxicities. Sequencing of therapies is important to individualize treatment decisions based on factors such as age, comorbidities, tolerability, and patient preferences. However, to date, there are limited data to guide the rational sequencing or combination of these therapies, since conventional chemoimmunotherapy or chemotherapy regimens were used as comparators against these small-molecule inhibitors in trials that led to their regulatory approvals. In this article, we examined and evaluated the current evidence for sequencing versus the combination of small-molecule inhibitors for CLL by conducting comprehensive searches of the United States National Library of Medicine PubMed database, key meeting abstracts, and clinical practice guidelines. We also summarized findings from expert opinions to elucidate best practices for clinical scenarios with limited evidence to guide treatment selection.

Recent applications of Kampo treatment for neurological diseases

AbstractBackgroundAlthough various new drugs have been developed for neurological diseases, many diseases have no effective treatment or only inadequate efficacy. Here we introduce some examples of effective Kampo treatment.Key Findings(1) Parasomnia in the elderly is preceded by the onset of diffuse Lewy body disease, with symptoms such as nightmares and loud screaming in the middle of the night. Keishikaryukotsuboreito (KSTRB), indicated in the classics for treating parasomnia, was effective in alleviating the symptoms. KSTRB is also used for enuresis that persists into adulthood. (2) Chronic subdural hematomas (CSDHs), treated by hematoma removal with burr‐hole surgery, recur at a rate of up to 20%. Goreisan (GRS) reduces hematoma volume and prevents postoperative CSDH recurrence. Homogeneous CSDH was most responsive to GRS in preventing recurrence. (3) Migraine frequently interferes with daily life. Keishibukuryogan (KBG), which alleviates blood stasis, was effective for patients with both menstruation‐associated migraine and scintillating scotomas. (4) Many traditional herbal medicines are listed in the Korean Medicine Clinical Practice Guideline for Stroke in Korea. Chunghyuldan, a related formula of Orengedokuto (OGT), is mainly used to prevent stroke.ConclusionKampo medicine is being applied in new and effective ways to treat various neurological diseases. Hopefully, more clinicians will recognize the usefulness of such Kampo medicines and utilize them in their daily practice.

A Framework on Developing an Integrative Medicine Clinical Practice Guideline (CPG) for Systemic Lupus erythematosus (SLE) with Comorbidities Management in Hong Kong

A Framework on Developing an Integrative Medicine Clinical Practice Guideline (CPG) for Systemic Lupus erythematosus (SLE) with Comorbidities Management in Hong Kong