Clinical Questions Research Articles

Application of near-infrared spectroscopy to assess the effect of the cupping size on the spatial hemodynamic response from the area inside and outside the cup of the biceps.

Cupping therapy is a popular intervention for improving muscle recovery after exercise although clinical evidence is weak. Previous studies demonstrated that cupping therapy may improve microcirculation of the soft tissue to accelerate tissue healing. However, it is unclear whether the cupping size could affect the spatial hemodynamic response of the treated muscle. The objective of this study was to use 8-channel near-infrared spectroscopy to assess this clinical question by assessing the effect of 3 cupping sizes (35, 40, and 45 mm in inner diameter of the circular cup) under -300 mmHg for 5 min on the muscle hemodynamic response from the area inside and outside the cup, including oxyhemoglobin and deoxy-hemoglobin in 18 healthy adults. Two-way factorial design was used to assess the interaction between the cupping size (35, 40, and 45 mm) and the location (inside and outside the cup) and the main effects of the cupping size and the location. The two-way repeated measures ANOVA demonstrated an interaction between the cupping size and the location in deoxy-hemoglobin (P = 0.039) but no interaction in oxyhemoglobin (P = 0.100), and a main effect of the cup size (P = 0.001) and location (P = 0.023) factors in oxyhemoglobin. For the cupping size factor, the 45-mm cup resulted in a significant increase in oxyhemoglobin (5.738±0.760 μM) compared to the 40-mm (2.095±0.312 μM, P<0.001) and 35-mm (3.134±0.515 μM, P<0.01) cup. Our findings demonstrate that the cupping size and location factors affect the muscle hemodynamic response, and the use of multi-channel near-infrared spectroscopy may help understand benefits of cupping therapy on managing musculoskeletal impairment.

Efficacy and safety of upstream unfractionated heparin compared with downstream administration in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention

Abstract Funding Acknowledgements None. Background Unfractionated heparin (UFH) is frequently administered before percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI)1,2. However, current guidelines do not provide clear recommendations for UFH pretreatment before arrival at the coronary catheterisation laboratory1,3. Methods Between June and July 2023, we systematically searched PubMed, Embase and Cochrane databases for studies comparing UFH pretreatments in patients with STEMI. A random-effects meta-analysis and meta-regression analyses were performed. Results Fourteen studies were included, of which four were randomised clinical trials (RCTs). A total of 76446 patients were included: 31238 in the pretreatment group and 39208 in the control group. Our meta-analysis revealed a lower all-cause mortality for the pretreatment strategy when compared with the control group, albeit with high heterogeneity (pooled odds ratio (OR) = 0.61, 95% confidence interval (CI) [0.49-0.76], P &amp;lt; 0.01; I² = 77%); lower in-hospital cardiogenic shock (pooled OR = 0.68, 95% CI [0.58-0.78], P &amp;lt; 0.21; I² = 27%) and a higher rate of spontaneous reperfusion events (pooled OR = 1.68, 95% CI [1.47-1.91], P &amp;lt; 0.01; I² = 79%). In terms of major bleeding, the UFH pretreatment strategy further revealed a decreased rate of events (pooled OR = 0.85, 95% CI [0.73-0.99], P = 0.40; I² = 4%). Conclusions From our study, UFH pretreatment in patients with STEMI undergoing primary PCI shows important benefits by reducing all-cause mortality, cardiogenic shock, enhancing reperfusion rates, whilst diminishing major bleeding events High-scale and high-quality RCTs will be required to fully address this clinical question in the future.1) Characteristics of included studies.2) Analyzed outcomes.

Which Diabetes Patients Will Benefit the Most from Once-Weekly Basal Insulin Analogs? A Review with a Special Focus on Type 1 Diabetes Patients

Basal insulin analogs, typically administered once or twice daily, have been one of the two pillars of the multiple daily injection (MDI) insulin therapy of patients with type 1 diabetes (T1D) for the last twenty years. Recently, once-weekly basal insulin analogs have been developed and are in late-phase clinical trials. One of these analogs is insulin icodec (icodec), appropriately developed to bind reversibly to albumin and to be gradually released into the patient’s circulation. Icodec has been tried mostly in clinical trials of adult patients with type 2 diabetes. A recent phase 3a clinical trial comprising adult patients with T1D was designed to evaluate icodec’s efficacy and safety compared with a daily basal insulin analog (degludec) after a 26-week main phase plus a safety extension of another 26 weeks. Icodec showed non-inferiority to once-daily degludec in glycated hemoglobin (HbA1c) reduction at week 26, and no significant differences in time in range (TIR) (70–180 mg/dL) and in time above range (TAR) (&gt;180 mg/dL). On the other hand, it was associated with increased rates of clinically significant hypoglycemia (blood glucose &lt; 54 mg/dL) and severe hypoglycemia (external assistance need for recovery), remaining either below or close to the internationally recommended targets for hypoglycemia. Another once-weekly insulin analog, basal insulin Fc (BIF), has been investigated in a phase 2 clinical trial comprising adult patients with T1D, with equally promising results. These preliminary data suggest that once-weekly insulin analogs could be of use for some patients with T1D, for example, patients not taking insulin regularly or those who are on MDI and wish for fewer injections. In addition, due to its prolonged mode of action, it could decrease the risk of diabetic ketoacidosis and the need for hospitalization. Additionally, patients with T1D that struggle with wearing diabetes mellitus devices/closed-loop insulin pumps either due to the cost or due to skin issues may also benefit from long-acting insulin. There is increasing evidence of the benefits of adjunctive therapies to insulin in T1D patients, but these therapies are not FDA-approved due to a possible higher risk of diabetic ketoacidosis. These long-acting insulin analogues could be used with adjunctive therapies in selected patients. This review aims to present available data on the mode of action, clinical trial results, and possible benefits of once-weekly insulin analogs for patients with T1D. In addition, it intends to suggest a future research framework for important clinical questions, such as once-weekly insulin analog use and exercise, sick days, or surgery, that will enhance our knowledge regarding this indisputable innovation in insulin management.

Evaluating and Comparing the Tensile Strength and Clinical Behavior of Monofilament Polyamide and Multifilament Silk Sutures: A Systematic Review

Objective: This systematic review was carried out with the primary objective of verifying which suture (polyamide or silk) of two non-resorbable suture materials with different structures had better/greater tensile strength/resistance to tension, thereby presenting better mechanical behavior. The secondary objective was to verify which one had better performance. The null hypothesis was that both types of sutures had the same behavior. Methods: This systematic study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The focused clinical question was: “In patients that underwent oral surgery treatment (P), is there significantly higher tensile strength/resistance for silk sutures (I) or for polyamide sutures (C) when comparing the outcomes (O)?” The bibliographic search was conducted on ScienceDirect, B-On, and PubMed/MedLine between March and May 2023. The following MeSH terms were defined: sutures, breaking strength, tensile strength, oral surgery, and dentistry, which were articulated and combined using Boolean operators. There were restrictions, such as articles published in Portuguese, Spanish, or English between 1 January 2018 and 3 April 2023. The quality assessment involved the use of the Joanna Briggs Institute (JBI) checklist for RCTs and the QUIN tool (Quality Assessment Tool For In Vitro Studies) for in vitro assays. Results: Ten articles were included in this review (eight in vitro studies and two RCTs). For the RCTs, there were moderate and high levels of bias, whereas in the in vitro studies, three were classified as having a high risk of bias and five as moderate risk. The results proved that suture thread with a monofilament polyamide physical structure causes a less inflammatory reaction owing to less bacterial retention and capillarity, while multifilament sutures, such as silk, have superior mechanical characteristics. Regarding hydration, the evidence demonstrated that the preservation and stability of mechanical properties lacked uniformity. Otherwise, hyaluronic acid (HA) presents a promising solution with the same characteristics and antibacterial capabilities. Conclusion: It was possible to reject the null hypothesis that both types of sutures had the same behavior and result. It was proven by the results above that sutures with a monofilament polyamide physical structure cause a less inflammatory reaction owing to less bacterial retention and capillarity. In contrast, multifilament sutures (silk) have superior mechanical characteristics. Regarding hydration using chlorohexidine in surgical sites, the evidence demonstrated in the preservation and stability of mechanical properties lacks uniformity and congruence. However, HA seems to present a promising option with the same characteristics and antibacterial capabilities.

Ultrasound assessment of the gravid cervix to assess for risk of spontaneous preterm birth: Introducing an evidence‐based clinical guideline for sonographers

AbstractThis article introduces a new evidence‐based clinical practice guideline (CPG) for sonographers; Ultrasound assessment of the gravid cervix to assess for risk of spontaneous preterm birth (sPTB). The purpose of this new CPG is to provide evidence‐based guidance for sonographers in Australia and New Zealand when making decisions on how and when they should sonographically assess the cervix in the gravid patient. Clinical questions relevant to the sonographic assessment of the gravid cervix were developed to inform the CPG. The primary sources to answer the clinical questions were relevant, existing CPGs. Recommendations in these existing CPGs were appraised for the level of evidence on which they were based and adapted for use in the new CPG. New recommendations were adapted from 19 existing CPGs rated as being based on best evidence and were applicable to three specific patient groups, each at different risk for sPTB. ‘How to Guidance’, statements about safety, acceptability, feasibility of ultrasound techniques, sonographer training and supplementary material were also developed using information from existing CPGs, relevant literature and the clinical experience of clinical guideline group members. The CPG recommendations, ‘how to guides’ and areas of future research are presented in this article. The full guideline and its supplementary materials are available at https://www.sonographers.org/resources-tools/clinical-guidance.

Evaluation of ChatGPT’s responses to information needs and information seeking of dementia patients

Many people in the advanced stages of dementia require full-time caregivers, most of whom are family members who provide informal (non-specialized) care. It is important to provide these caregivers with high-quality information to help them understand and manage the symptoms and behaviors of dementia patients. This study aims to evaluate ChatGPT, a chatbot built using the Generative Pre-trained Transformer (GPT) large language model, in responding to information needs and information seeking of such informal caregivers. We identified the information needs of dementia patients based on the relevant literature (22 articles were selected from 2442 retrieved articles). From this analysis, we created a list of 31 items that describe these information needs, and used them to formulate 118 relevant questions. We then asked these questions to ChatGPT and investigated its responses. In the next phase, we asked 15 informal and 15 formal dementia-patient caregivers to analyze and evaluate these ChatGPT responses, using both quantitative (questionnaire) and qualitative (interview) approaches. In the interviews conducted, informal caregivers were more positive towards the use of ChatGPT to obtain non-specialized information about dementia compared to formal caregivers. However, ChatGPT struggled to provide satisfactory responses to more specialized (clinical) inquiries. In the questionnaire study, informal caregivers gave higher ratings to ChatGPT's responsiveness on the 31 items describing information needs, giving an overall mean score of 3.77 (SD 0.98) out of 5; the mean score among formal caregivers was 3.13 (SD 0.65), indicating that formal caregivers showed less trust in ChatGPT's responses compared to informal caregivers. ChatGPT’s responses to non-clinical information needs related to dementia patients were generally satisfactory at this stage. As this tool is still under heavy development, it holds promise for providing even higher-quality information in response to information needs, particularly when developed in collaboration with healthcare professionals. Thus, large language models such as ChatGPT can serve as valuable sources of information for informal caregivers, although they may not fully meet the needs of formal caregivers who seek specialized (clinical) answers. Nevertheless, even in its current state, ChatGPT was able to provide responses to some of the clinical questions related to dementia that were asked.

Abstract PO3-13-09: Personalized ctDNA testing for detection of molecular residual disease in patients with localized HR+ breast cancer: temporal dynamics and impact on clinical outcomes

Abstract Background: Molecular residual disease (MRD) describes detectable circulating tumor DNA (ctDNA) after definitive surgery and is an expanding field in breast oncology. Multiple studies have demonstrated detectable MRD to be poorly prognostic, and clinical trials are now underway assessing the efficacy of therapeutic interception. However, most retrospective studies did not obtain baseline imaging at the time of MRD detection, such that the proportion of patients with detectable ctDNA and concurrent radiographically evident recurrent disease is not known. Furthermore, the role of serial ctDNA testing in the adjuvant setting remains unclear. Meanwhile, tumor-informed assays such as the SignateraTM platform are now covered by Medicare. To address these outstanding clinical questions, we aimed to determine the temporal dynamics of MRD detection in HR+/HER2- breast cancer, association with radiographic recurrence, and impact on clinical outcomes. Methods: Patients with HR+/HER2- breast cancer who underwent MRD testing either as part of a clinical trial or via an expanded access program were reviewed for MRD positivity and assessed alongside clinically annotated data. All patients completed surgical resection prior to MRD testing. Whole exome sequencing of primary tumor tissue and personalized ctDNA primers were designed for multiplex PCR targeting up to 16 single nucleotide variants for MRD testing via the SignateraTM platform. Clinical data was determined through focused chart review. Results: Among 185 patients with HR+/HER2- breast cancer who underwent MRD testing, 37 patients (20%) did not complete testing due to factors including tumor tissue not meeting pathology parameters, insufficient quantity of primary tissue, or tumor/normal discordance. 14 patients (8%) had detectable ctDNA (1, 5, and 8 patients had stage I, II, and III breast cancer, respectively). Among the 6 patients who did not have stage III disease, 3 had other high-risk features (Oncotype 40; grade 3 disease x2). Overall, 71% (n=10) of the +MRD population tested positive at the first test, while 29% (n=4) tested positive only on serial sampling. Median time from surgery to positive test was 3.5 years (range: 1 month – 10.2 years). Twelve patients (86%) were on adjuvant endocrine therapy at the time of detectable MRD. Among the 14 +MRD patients, 9 underwent staging scans shortly after positive MRD testing, and among these patients, 3 (33%) had radiographic evidence of asymptomatic metastatic recurrence (2 bone-only; 1 visceral); two of these pts had 1 MRD test, while the other had a negative test followed by a positive test 11 months later. The other 3 patients with radiographic recurrences had scans prompted only by clinical symptoms &amp;gt;6 months after +MRD. Among the 4 patients with serial data after first +MRD testing, none experienced subsequent ctDNA clearance. Serial testing occurred over a median of 11.5 months (range 1.1-21.7 months). With median follow up of 8.6 months, 43% (n=6) of patients with +MRD had distant disease recurrence. Conclusions: Personalized tumor-informed ctDNA testing identified patients with high risk of recurrence, including patients without classic high-risk clinical, pathologic, or genomic features, suggesting a complementary role of MRD testing for risk assessment. Serial monitoring was necessary to identify MRD in more than a quarter of patients. Furthermore, one-third of patients with +MRD disease had asymptomatic metastatic recurrence, highlighting the importance of staging scans in studies and clinical trials assessing therapeutic interception in the adjuvant setting. Citation Format: Arielle Medford, Elyssa Denault, Zanta Ephrem, Douglas Micalizzi, Yael Bar, Rachel Abelman, Amy Comander, Justine Knape, Minetta Liu, Angel Rodriguez, Steven Isakoff, Beverly Moy, Laura Spring, Aditya Bardia. Personalized ctDNA testing for detection of molecular residual disease in patients with localized HR+ breast cancer: temporal dynamics and impact on clinical outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-09.

Rogue Hairs: A Mixed-Method Characterization of a Previously Unreported Entity

Plain Language SummaryThis research defines a new term called “rogue hairs” which are unusually long hairs on the face outside of the places where long hairs typically grow. These hairs are common but were not previously reported in medical literature. This study describes how often these hairs occur, where they occur, and other details about the people who have them. People with rogue hairs were identified by dermatologists, and social media platforms were searched to find additional people with these hairs. This study also used surveys and social media websites to learn about people with these hairs. The results showed that these hairs are seen in children and adults, men and women, and across races. Eighteen percent of the surveyed patients reported rogue hairs. Social media analysis showed common experiences of sudden appearance, frequent attempts to remove the hairs, and minimal interaction with dermatologists. The cause for these hairs is not known. This study highlights the potential of social media as a tool for answering clinical questions and better understanding the patient experience. The study provides evidence-based information for individuals experiencing rogue hairs and prompts future research into the causes of this common phenomenon.

Abstract PO3-19-01: A Randomized Controlled Trial of Metastasis-directed Therapy for Oligometastases in Breast Cancer (OLIGAMI trial; JCOG2110)

Abstract Background: Oligometastases were initially described as a concept bridging localized disease with widespread distant metastases, but a consensus on its definition has yet to be reached. Recently, the term "metastasis-directed therapy" (MDT) was coined to encompass local therapy for distant metastases, including surgery and radiation therapy (RT), especially stereotactic body radiation therapy (SBRT). Though OLIGO-BC1 and SABR-COMET have indicated the potential benefits of MDT for oligometastases, NRG-BR002 revealed no significant difference in progression-free survival (PFS). As a definitive conclusion to this clinical question has not been reached, there is an increasing demand for phase III trials focusing on breast cancer (BC). We planned the JCOG2110, also called as OLIGAMI trial . Design: OLIGAMI trial is a multi-institutional, two-arm, open-label, randomized controlled phase III trial being conducted with the participation of 50 hospitals belonging to Japan Clinical Oncology Group. After the first registration, all patients will be performed in a 12-week, subtype-specific, systemic therapy consisting of CDK4/6 inhibitors with hormonal therapy for luminal BC, docetaxel with trastuzumab and pertuzumab for HER2-positive BC, chemotherapy with immune checkpoint inhibitors for triple-negative BC expressing PD-L1, and olaparib for cases harboring BRCA mutations. For other triple-negative BC, chemotherapy will be administered. If this 12-week systemic therapy dose not cause any progression or complete response, patients proceed to second registration for randomization; arm A continues same systemic therapy alone, and arm B performs MDT followed by same systemic therapy. The MDT will involve either RT or surgery, and RT will involve mainly SBRT and partly conventional RT. Eligibility criteria: OLIGAMI trial will encompass all subtypes of advanced BC. The key criteria of the first registration are as follows: 1) Histologically diagnosed as invasive BC. Biopsy from oligometastases is desirable but not required. 2) Diagnosed with advanced BC with oligometastases by neck to pelvis enhanced CT, FDG-PET, and brain enhanced MRI. 3) Oligometastases defined as: (i) Maximum diameter of each tumor is 3 cm or less. (ii) Total number of 3 or less. (iii) In case of brain metastasis, maximum diameter is 2 cm or less and asymptomatic. 4) The patient with local recurrence is included. 5) De novo stage IV BC is included. The criteria of secondary registration are as follows: 1) The planned number of courses of systemic therapy has been performed. 2) No progression or new distant metastasis by response evaluation. 3) At least one oligometastaseis remains. Specific Aims: OLIGAMI trial aims to confirm the superiority of MDT to systemic therapy for oligometastases of BC. The primary endpoint is overall survival (OS) after randomization, while the secondary endpoints include OS after first registration, PFS, progression site (oligometastases vs. non-oligometastases), PFS specifically related to MDT (restricted arm B), proportion of adverse events and serious adverse events, and the non-progression proportion of health-related quality of life. Statistical methods: The sample size was calculated as 268 to detect 12% of 5-year OS difference with one-sided alpha of 0.05, power of 70%, 3 years of accrual, and 5 years of follow up. Therefore, we assumed the planned sample size for second registration for randomization as 270. We set the number of first registration as 340, assuming that there may be some patients with progression or complete response after the systemic therapy for 12 weeks. Present accrual and target accrual: The patient accrual will start in August 2023. Enrolment of 340 patients for first registration is planned over a 3-year accrual period. Contact information: Principal investigator, Toshiyuki Ishiba, MD. Ph.D. ishiba0313@gmail.com Citation Format: Toshiyuki Ishiba, Ikuno Nishibuchi, Fumitaka Hara, Keita Sasaki, Ryo Sadate, Yuta Sekino, Ryunosuke Machida, Haruhiko Fukuda, Takahiro Kogawa, Tomomi Fujisawa, Yasuaki Sagara, Yoichi Naito, Kaori Terata, Yukinori Ozaki, Akihiko Shimomura, Takehiko Sakai, Chizuko Kanbayashi, Tsuguo Iwatani, Hideo Shigematsu, Kenji Tamura, Takashi Mizowaki, Michio Yoshimura, Naoto Shikama, Tadahiko Shien, Hiroji Iwata. A Randomized Controlled Trial of Metastasis-directed Therapy for Oligometastases in Breast Cancer (OLIGAMI trial; JCOG2110) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-01.

Therapeutic use of granulocyte colony-stimulating factor (G-CSF) in patients with febrile neutropenia: a comprehensive systematic review for clinical practice guidelines for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question. The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case-control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain. The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27-2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible. A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk.

What Should Healthcare Systems Consider When Modernizing Call Centers? Early Considerations From the Veterans Health Administration.

Growing numbers of hospitals and payers are using call centers to answer patients' clinical and administrative questions, schedule appointments, address billing issues, and offer supplementary care during public health emergencies and national disasters. In 2020, the Veterans Health Administration (VA) implemented VA Health Connect, an enterprise-wide initiative to modernize call centers. VA Health Connect is designed to improve the care experience with the convenience, flexibility, and simplicity of a single toll-free number connected to a range of 24/7 virtual services. The services are organized into four areas: administrative guidance for scheduling and general inquiries; pharmacy support for medication matters; clinical triage for evaluation of symptoms and recommended care; and virtual visits with providers for urgent and episodic care. Through a qualitative evaluation of VA Health Connect, we sought to identify the factors that affected the development of this program and to compile considerations to support the implementation of other enterprise-wide initiatives. The evaluation team interviewed 29 clinical and administrative leads from across the VA. These leads were responsible for the modernization of their local service networks. PhD-level qualitative methodologists conducted the interviews, asking participants to reflect on barriers and facilitators to modernization and implementation. The team employed a rapid qualitative analytic approach commonly used in healthcare research to distill robust results. A review of the early implementation of VA Health Connect found: (1) deadlines proved challenging but provided momentum for the initiative; (2) a balance between standardized processes and local adaptations facilitated implementation; (3) attention to staffing, hiring, and training of call center staff before implementation expedited workflows; (4) establishing national and local leadership commitment to the innovation from the onset increased team cohesion and efficacy; and (5) anticipating information technology infrastructure needs prevented delays to modernization and implementation. Our findings suggest that healthcare systems would benefit from anticipating likely obstacles (e.g., delays in software implementations and negotiations with unions), thus providing ample time to secure leadership buy-in and identify local champions, communicating early and often, and supporting flexible implementation to meet local needs. VA leadership can use this evaluation to refine implementation, and it could also have important implications for regulators, federal health exchanges, insurers, and other healthcare systems when determining resource levels for call centers.

Efficacy of clear aligner therapy over conventional fixed appliances in controlling orthodontic movement: A systematic review

OBJECTIVE: The purpose of the current systematic review was to answer the clinical research question “Is Clear Aligner Therapy (CAT) effective in controlling the orthodontic movement?” by bringing together the most up-to-date information about the available evidence for CAT. METHODOLOGY: On January 1, 2023, a search was conducted in PubMed, ERIC, Embase, and CINHAL for any research papers published in the previous 10 years that provided an overview of the PICO questions. Both the titles and abstracts of the selected studies were evaluated independently by two different authors, and if there was any disagreement between the two review authors, a third reviewer was brought in to settle it. RESULTS: Among included studies, three were retrospective non-randomized and two studies were prospective randomized clinical trials. Various authors reported better outcome for fixed orthodontic appliances than for clear aligner treatment (CAT) in relation to mandibular incisor proclination. The mean objective grading system score was better for braces (17) than for CAT (12) with no clinically significant difference, while staging had a significant impact on treatment efficacy. CONCLUSION: The results of this study suggest that clear aligners may be an effective alternative to traditional braces, but more research is needed to confirm these findings and determine the optimal size of future prospective studies evaluating this treatment.

Practical Answers to Frequently Asked Questions in Anterior Cervical Spine Surgery for Degenerative Conditions.

Surgical counseling enables shared decision making and optimal outcomes by improving patients' understanding about their pathologies, surgical options, and expected outcomes. Here, we aimed to provide practical answers to frequently asked questions (FAQs) from patients undergoing an anterior cervical diskectomy and fusion (ACDF) or cervical disk replacement (CDR) for the treatment of degenerative conditions. Patients who underwent primary one-level or two-level ACDF or CDR for the treatment of degenerative conditions with a minimum of 1-year follow-up were included. Data were used to answer 10 FAQs that were generated from author's experience of commonly asked questions in clinic before ACDF or CDR. A total of 395 patients (181 ACDF, 214 CDR) were included. (1, 2, and 3) Will my neck/arm pain and physical function improve? Patients report notable improvement in all patient-reported outcome measures. (4) Is there a chance I will get worse? 13% (ACDF) and 5% (CDR) reported worsening. (5) Will I receive a significant amount of radiation? Patients on average received a 3.7 (ACDF) and 5.5 mGy (CDR) dose during. (6) How long will I stay in the hospital? Most patients get discharged on postoperative day one. (7) What is the likelihood that I will have a complication? 13% (8% minor and 5% major) experienced in-hospital complications (ACDF) and 5% (all minor) did (CDR). (8) Will I need another surgery? 2.2% (ACDF) and 2.3% (CDR) of patients required a revision surgery. (9 & 10) When will I be able to return to work/driving? Most patients return to working (median of 16 [ACDF] and 14 days [CDR]) and driving (median of 16 [ACDF] and 12 days [CDR]). The answers to the FAQs can assist surgeons in evidence-based patient counseling.

Saudi National Clinical Practice Guidelines for Management of Adult Systemic Lupus Erythematosus.

To provide evidence-based clinical practice recommendations for managing Systemic Lupus Erythematosus (SLE) in Saudi Arabia. This EULAR-adapted national guideline in which a multidisciplinary task force utilized the modified Delphi method to develop 31 clinical key questions. A systematic literature review was conducted to update the evidence since the EULAR publication. After reaching a consensus agreement, two rounds of voting and group discussion were conducted to generate consolidated recommendations/statements. A significant number of patients in Saudi Arabia experience delays in accessing rheumatologists, highlighting the significance of timely referral to SLE specialists or rheumatologists to ensure accurate diagnosis and prompt treatment. The primary goal of Glucocorticoid (GC) therapy in SLE patients is to establish disease control with a minimum dose and duration. Steroid-sparing agent utilization facilitates steroid-sparing goals. Hydroxychloroquine is recommended for all SLE patients, though physicians must carefully monitor toxicity and prioritize regular medication adherence assessment. SLE management during pregnancy starts from preconception time by assessing disease activity, major organ involvement, hypercoagulability status, and concomitant diseases that may negatively impact maternal and fetal outcomes. Multidisciplinary care with close monitoring may optimize both maternal and fetal outcomes. For patients with antiphospholipid antibodies, low-dose aspirin prophylaxis is recommended. Also, Long-term anticoagulant medications are fundamental to prevent secondary antiphospholipid syndrome due to high thrombosis recurrence. This Saudi National Clinical Practice guidelines for SLE management provide evidence-based recommendations and guidance for healthcare providers in Saudi Arabia who are managing patients with SLE. These guidelines will help to standardize healthcare service, improve provider education, and perhaps lead to better treatment outcomes for SLE patients.

Performance of ChatGPT in Answering Clinical Questions on the Practical Guideline of Blepharoptosis.

ChatGPT is a free artificial intelligence (AI) language model developed and released by OpenAI in late 2022. This study aimed to evaluate the performance of ChatGPT to accurately answer clinical questions (CQs) on the Guideline for the Management of Blepharoptosis published by the American Society of Plastic Surgeons (ASPS) in 2022. CQs in the guideline were used as question sources in both English and Japanese. For each question, ChatGPT provided answers for CQs, evidence quality, recommendation strength, reference match, and answered word counts. We compared the performance of ChatGPT in each component between English and Japanese queries. A total of 11 questions were included in the final analysis, and ChatGPT answered 61.3% of these correctly. ChatGPT demonstrated a higher accuracy rate in English answers for CQs compared to Japanese answers for CQs (76.4% versus 46.4%; p = 0.004) and word counts (123 words versus 35.9 words; p = 0.004). No statistical differences were noted for evidence quality, recommendation strength, and reference match. A total of 697 references were proposed, but only 216 of them (31.0%) existed. ChatGPT demonstrates potential as an adjunctive tool in the management of blepharoptosis. However, it is crucial to recognize that the existing AI model has distinct limitations, and its primary role should be to complement the expertise of medical professionals. Observational study under respected authorities. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

2023 clinical practice guidelines on autism spectrum disorder in children and adolescents in Singapore

Introduction: Autism is a neurodevelopmental condition that is increasing in prevalence worldwide. There has been an exponential increase in autism-related research since 2010, when the first Singapore Clinical Practice Guidelines (CPG) on autism was published. Understanding of autism has since evolved to adopt a lifespan approach beyond that of a childhood condition. The aim of this CPG was to provide an updated set of recommendations for children and adolescents to aid clinical practice for professionals. Method: A multidisciplinary workgroup that comprised representatives from various sectors worked on this CPG. Clinical questions were organised into 10 different sections, each with its own subgroup of members. Seventeen existing international guidelines were evaluated using the Appraisal of Guidelines for REsearch &amp; Evaluation II (AGREE-II) framework, of which 4 met criteria to act as references. Literature review across multiple databases was conducted between January 2011 to 2023; Grading of Recommendations, Assessment, Development and Evaluation (GRADE-like) methodology was used to synthesise evidence. Recommendation statements were derived, following Delphi-style consensus surveys among the workgroup. The draft guidelines underwent external review and public consultation before being formalised. Results: Recommendation and good practice statements pertaining to care of children and adolescents on the autism spectrum across 10 different sections were developed. Evidence matrices complement these recommendations and detail relevant evidence behind each recommendation statement. Conclusion: It is intended for these guidelines to promote effective management and healthcare services for children and adolescents on the autism spectrum, by reinforcing good and evidence-based clinical practice within our national context.

A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics with Metabolism, Signaling Networks, and Biomechanics as Plug-In Component Models of a Cancer Digital Twin

The massive amount of human biological, imaging, and clinical data produced by multiple and diverse sources necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell-signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels, as well as their orchestration and links, are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof-of-concept study cases. Personalized simulations of the actual anatomy of a patient have been conducted. The hypermodel has also been applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin-based clinical decision support system and as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary.

Meta-analyses in cholestatic pregnancy: The outstanding clinical questions

Reports of adverse pregnancy outcomes associated with maternal pruritus and liver impairment have circulated since the 1800s, yet the precise diagnosis and management of intrahepatic cholestasis of pregnancy have varied markedly. Recent evidence, including that from individual participant data meta-analyses, has provided an evidence that brings us closer to standardised, and optimal, management of the condition. Based upon increased adverse perinatal outcomes with higher bile acid concentrations, disease management should be according to severity (defined by peak bile acid concentration) in order to recommend appropriate gestation of birth. Similarly, the reduced spontaneous preterm birth rate for patients receiving ursodeoxycholic acid treatment suggests potential benefit for the treatment of patients with moderate-severe disease.

The use of master protocols for efficient trial design to evaluate radiotherapy interventions: a systematic review.

The aim of this review was to highlight why the use of master protocols trial design is particularly useful for radiotherapy intervention trials where complex-set up pathways (including quality assurance, user training, integrating multiple modalities of treatment) may hinder clinical advances. We carried out a systematic review according to PRISMA guidelines, reviewing the findings using a landscape analysis. Results were summarised descriptively, reporting on trial characteristics highlighting the benefits, limitations, and challenges of developing and implementing radiotherapy master protocols with three case studies selected to explore these issues in more detail. 12 studies were suitable for inclusion (4 platform trials, 3 umbrella trials, and 5 basket trials), evaluating a mix of solid tumour sites in both curative and palliative settings. The interventions were categorised into 1. Novel agent and radiotherapy combinations; 2. Radiotherapy dose personalisation; and 3. Device evaluation, with a case study provided for each intervention. Benefits of master protocol trials for radiotherapy intervention include: protocol efficiency for implementation of novel radiotherapy techniques; accelerating the evaluation of novel agent drug and radiotherapy combinations; and more efficient translational research opportunities, leading to cost savings and research efficiency to improve patient outcomes. Master protocols offer an innovative platform under which multiple clinical questions can be addressed within a single trial. Due to the complexity of radiotherapy trial set up, cost and research efficiency savings may be more apparent than in systemic treatment trials. Use of this research approach may be the change needed to push forward oncological innovation within radiation oncology.

From Bytes to Best Practices: Tracing ChatGPT-3.5's Evolution and Alignment With the National Comprehensive Cancer Network® Guidelines in Pancreatic Adenocarcinoma Management.

Artificial intelligence continues to play an increasingly important role in modern health care. ChatGPT-3.5 (OpenAI, San Francisco, CA) has gained attention for its potential impact in this domain. To explore the role of ChatGPT-3.5 in guiding clinical decision-making specifically in the context of pancreatic adenocarcinoma and to assess its growth over a period of time. We reviewed the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines for the Management of Pancreatic Adenocarcinoma and formulated a complex clinical question for each decision-making page. ChatGPT-3.5 was queried in a reproducible fashion. We scored answers on the following Likert scale: 5) Correct; 4) Correct, with missing information requiring clarification; 3) Correct, but unable to complete answer; 2) Partially incorrect; 1) Absolutely incorrect. We repeated this protocol at 3-months. Score frequencies were compared, and subgroup analysis was conducted on Correctness (defined as scores 1-2 vs 3-5) and Accuracy (scores 1-3 vs 4-5). In total, 50-pages of the NCCN Guidelines® were analyzed, generating 50 complex clinical questions. On subgroup analysis, the percentage of Acceptable answers improved from 60% to 76%. The score improvement was statistically significant (Mann-Whitney U-test; Mean Rank = 44.52 vs 56.48, P = .027). ChatGPT-3.5 represents an interesting but limited tool for assistance in clinical decision-making. We demonstrate that the platform evolved, and its responses to our standardized questions improved over a relatively short period (3-months). Future research is needed to determine the validity of this tool for this clinical application.