Clinical Summary Research Articles

Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program

BackgroundInflammation is thought to be an important mechanism for the development and progression of obesity-related heart failure with preserved ejection fraction (HFpEF). In the STEP-HFpEF Program, once-weekly 2.4 mg semaglutide improved heart failure–related symptoms, physical limitations, and exercise function, reduced the levels of C-reactive protein (CRP), a biomarker of inflammation, and reduced body weight in participants with obesity-related HFpEF. However, neither the prevalence nor the clinical characteristics of patients who have various magnitudes of inflammation in the context of obesity-related HFpEF have been well described. Furthermore, whether the beneficial effects of semaglutide on the various HF efficacy endpoints in the STEP-HFpEF Program are modified by the baseline levels of inflammation has not been fully established. Finally, the relationship between weight reduction and changes in CRP across the STEP-HFpEF Program have not been fully defined. ObjectivesThis study sought to: 1) evaluate baseline characteristics and clinical features of patients with obesity-related HFpEF that have various levels of inflammation in the STEP-HFpEF Program; 2) determine if the effects of weekly semaglutide 2.4 mg vs placebo across all key outcomes are influenced by baseline levels of inflammation assessed by CRP levels; and 3) determine the relationship between change in CRP and weight loss in the STEP-HFpEF Program. MethodsThis was a secondary analysis of pooled data from 2 international, double-blind, placebo-controlled, randomized trials (STEP-HFpEF and STEP-HFpEF DM). The outcomes were change in the dual primary endpoints (health status [measured by the Kansas City Cardiomyopathy Questionnaire—Clinical Summary Score (KCCQ-CSS)] and body weight) from baseline to 52 weeks according to baseline CRP levels. Additional efficacy endpoints included change in 6-minute walk distance (6MWD), a hierarchical composite endpoint that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6MWD, and levels of CRP in semaglutide- vs placebo-treated patients. Patients were stratified into 3 categories based on baseline CRP levels (<2, ≥2 to <10, and ≥10 mg/L). ResultsIn total, 1,145 patients were randomized, of which 71% of patients had evidence of inflammation (CRP ≥2 mg/L). At baseline, those with higher levels of inflammation were younger, were more likely to be female, and had higher body mass index, worse health status (KCCQ-CSS), and shorter 6MWD. Semaglutide vs placebo led to reductions in HF-related symptoms and physical limitations as well as body weight, and to improvements in 6MWD and the hierarchical composite endpoint that were consistent across baseline CRP categories (all P interaction nonsignificant). Semaglutide also reduced CRP to a greater extent than placebo regardless of baseline CRP levels (P interaction = 0.32). Change in CRP from baseline to 52 weeks was similar regardless of the magnitude of weight loss (P interaction = 0.91). ConclusionsInflammation is highly prevalent in obesity-related HFpEF. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced body weight across the categories of baseline CRP. Semaglutide also reduced inflammation, regardless of either baseline CRP or magnitude of weight loss during the trials. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF; NCT04788511]; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM; NCT04916470])

Teething - filling in the gaps….

Dentists and dental care professionals may be faced with concerns from parents and carers regarding teething in infants and young children. Teething is a normal physiological and self-limiting process; however, the diverse signs and symptoms that have, over time, been attributed to teething, can make diagnosis challenging. Appropriate diagnosis is crucial in preventing the potentially life-threatening sequalae of dismissing symptoms as teething and delaying appropriate treatment of a systemically unwell child. Management of teething can be approached in a five-step process based on the National Institute for Health and Care Excellence clinical knowledge summary on teething. These include: 1) history-taking, clinical examination, diagnosis and referral of systemically unwell or severely distressed children for urgent medical review; 2) providing parental/carer reassurance, information and preventative advice; 3) simple, non-pharmacological management strategies; 4) pharmacological intervention; 5) safety-netting advice in case the child becomes systemically unwell, has prolonged symptoms, or is in severe distress. The purpose of this article is to bridge knowledge gaps regarding teething to enable appropriate diagnosis and encourage dissemination of preliminary information and ensure appropriate referral by frontline dental professionals.

Safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy: A 36-week analysis from FOREST-HCM.

The aim of this study was to report safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) over 36 weeks in the ongoing FOREST-HCM trial. Patients were started on aficamten 5 mg daily, with doses adjusted in 5-mg increments (5-20 mg) at ≥2-week intervals according to site-read left ventricular ejection fraction (LVEF). Aficamten dose was increased if LVEF ≥55%, maintained if LVEF 50-54%, decreased if LVEF 40-<50%, and temporarily interrupted if LVEF <40%. Safety and efficacy were assessed over 36 weeks. Overall, 34 patients were enrolled (mean age 57.2 ± 15.3 years, 62% female, 41% in New York Heart Association [NYHA] class III). Over 36 weeks, 82.3% achieved 15-20 mg daily dose and there was a modest reduction in LVEF by -4.3% ± 5.2 from 70% ± 6.1 (p < 0.0001). At Week 36, NYHA class improved by ≥1 class in 27 (79.4%) patients. Mean Kansas City Cardiomyopathy Questionnaire clinical summary score improved by 13.8 ± 12.5 points relative to baseline. Median (interquartile range) levels of N-terminal pro-B-type natriuretic peptide were significantly improved from baseline (-665.5 pg/ml [-1244.0, -232.0]; p < 0.0001), while high-sensitivity cardiac troponin I was unchanged (-2.7 ng/L [-11.3, 1.6]; p = 0.25). There were no drug discontinuations due to adverse events. LVEF <50% occurred in 2 (5.9%) patients, one following pulmonary vein isolation and one associated with atrial fibrillation. Over 36 weeks, aficamten appeared safe and effective in the studied patients with nHCM.

Semaglutide in Heart Failure: A Systematic Review of Outcomes of Semaglutide in Heart Failure Patients.

Heart failure (HF) stands as a formidable challenge in global healthcare casting a long shadow over both morbidity and mortality. A significant interplay between HF and type 2 diabetes (T2DM) manifests an elevated risk of adverse cardiovascular events in T2DM patients. Glucagon-like peptide 1emerges as a pivotal player in T2DM, which is released in response to meals rich in glucose and lipids. We aim to assess the outcomes of using semaglutide in HF. A comprehensive literature search was performed using electronic databases, including PubMed/Medline, the Cochrane Library, and Google Scholar, covering all records up to May 10, 2024. Studies meeting inclusion criteria were selected. Qualitative analysis was conducted to analyze the findings of the studies included. Four studies (three randomized controlled trials and one observational study) were included in our manuscript.There was a significant decrease in the Kansas City Cardiomyopathy Questionnaire clinical summary score (p< 0.001), body weight (p< 0.001), six-minute walk distance (p< 0.001), and CRP levels (p< 0.001). A statistically significant decrease in overall major adverse cardiac events was observed with a hazardratio of 0.76 (95% CI 0.62, 0.92). Other factors and adverse effects were also discussed in our manuscript. Our study showed that semaglutide resulted in improvement in HF patients. Although adverse effects were observed,theywere not as significant as the placebo itself.

Office- versus home-based evaluation of quality of life in heart failure with reduced ejection fraction: A randomized study

BackgroundHeart failure (HF) patients often experience poor health-related quality-of-life (HR-QoL). The Kansas City Cardiomyopathy Questionnaire (KCCQ) is frequently used for assessing HR-QoL in HF. Whether KCCQ scores vary in a clinical meaningful manner according to the setting (home vs office) where patients respond to the questionnaire is currently unknown. AimsAssess the differences in the responses to KCCQ-23 questionnaire when completed at home or office. MethodsRandomized parallel-group study, including patients with HF with reduced ejection fraction (HFrEF). Primary outcome was home vs office comparison of overall summary score (KCCQ-OSS). Main secondary outcomes were clinical summary score (KCCQ-CSS) and total symptom score (KCCQ-TSS). ResultsA total of 100 patients were included in the study: 50 home vs 50 office. Mean age was 71 yrs. Most baseline characteristics were well balanced between groups, except male sex, MRA use, and prior HF hospitalizations which were more frequent in the home group. No statistically-significant between-group differences were found regarding KCCQ-OSS (median [percentile25–75]) scores: home 69.1 (42.0–86.5) vs office 63.1 (44.3–82.3) points, P-value = 0.59, or main secondary outcomes: KCCQ-CSS home 62.2 (46.5–79.9) vs office 68.1 (51.9–79.2) points, P-value = 0.69, and KCCQ-TSS home 84.7 (59.7–97.2) vs office 76.4 (66.7–94.4) points, P-value = 0.85. Results remained similar after adjustment for differences in baseline characteristics and using non-parametric regressions. ConclusionsNo major differences were found in KCCQ-23 scores regardless of whether the questionnaire was completed at home or office. These findings can be useful to make HR-QoL more accessible, allowing patients to respond at home using email or cell-phone applications.

P-205 Exploring the influence of platelet rich plasma (PRP) versus PRP with hyaluronic acid on endometrial thickness (ET) and IVF outcome: a pilot study

Abstract Study question What is the impact of sub-endometrial instillation of PRP versus PRP with hyaluronic acid on ET and IVF outcome defined by positive and clinical pregnancy Summary answer PRP with hyaluronic acid group had more endometrial thickness with better vascularity and better pregnancy outcomes as compared to normal PRP What is known already Receptive endometrium is the end result of an interplay of a myriad of cytokines, adhesion molecules growth factors etc. Defect in these can result in thin endometrium. Sub endometrial PRP instillation has been attempted in such cases with promising results and acts by stimulating cell growth and angiogenesis These actions are enhanced by hyaluronic acid along with its antiadhesive effect. PRP with hyaluronic acid has been used previously in orthopedics, dermatology but not documented in thin endometrium. Most of previous studies have focused on endometrial thickness and no comparison has been done between PRP and PRP with hyaluronic acid. Study design, size, duration A retrospective observational study was conducted at Gunjan IVF WORLD Ghaziabad, from January 2022 to Dec 2023. Total 215 patients between the age group of 21-50 years with thin endometrium (ET &amp;lt; 7mm) with zone 2 or less vascularity with at least 1 good quality blastocyst for transfer were selected. They were subjected to hysteroscopic sub endometrial PRP instillation or instillation of PRP with hyaluronic acid Participants/materials, setting, methods Women with diverse reasons for infertility were divided into 2 groups - those receiving PRP (87 subjects) vs PRP with hyaluronic acid (128 subjects). PRP was activated by adding 0.1 ml of Calcium Chloride in 0.9 ml of PRP. Hyaluronic acid (80IU/ML) was added to PRP in the ratio of 1:5. The two groups were compared for positive pregnancy defined as βhCG &amp;gt;100 mIU/ml, clinical pregnancy defined as visualization of gestational sac and endometrial thickness Main results and the role of chance 112 of 215 (52.09%) women had positive pregnancy outcomes (βhCG &amp;gt;100 mIU/ml). Of the 112 subjects having positive outcomes, 40 (35.71%) belonged to normal PRP group and 72 (64.28%) belonged to PRP with hyaluronic acid group. Clinical pregnancy was seen in 37 (33.03%) in normal PRP group and 70(62.5%) in PRP with hyaluronic acid group. Mean βhCG was significantly higher in PRP with hyaluronic acid group (p = 0.013). Mean endometrial thickness was also higher in PRP with hyaluronic acid group (p = 0.05). The findings of the study suggest that PRP with hyaluronic acid has much better results in patients with thin endometrium in terms of not only the endometrial thickness but it also translates into better pregnancy rates. Limitations, reasons for caution 1. Patient pool from limited geographical area. 2. More Randomized controlled trials with larger sample size required to assess efficacy of Platelet rich plasma with hyaluronic acid. 3. The results were analyzed only up to clinical pregnancy and not ongoing pregnancy or live birth rates Wider implications of the findings 1. PRP with hyaluronic acid can be a boon to patients having thin endometrium who otherwise would have sub optimal IVF outcomes 2. Study can encourage larger randomized controlled trials in this direction especially in cases of intrauterine adhesions. Trial registration number not applicable

1021 Accuracy of Clinical Coding in General Surgery and Its Financial Impact

Abstract Aim To analyse the clinical coding performed at a tertiary centre after patient discharge and compare it with the clinical summary to identify any inconsistency and its financial implications. Method Fifty patient episodes were selected randomly between June 2023 and August 2023 under the general surgery department. Clinical notes, discharge summaries and existing clinical codes were scrutinized by liaison with the clinical coding department. Financial losses were noted, and the summary was later presented at the local clinical governance meeting. Results A total of £38,760 was lost in 50 patients. Loss incurred was primarily due to incomplete information in the discharge summary, related to the patient’s comorbidities, incomplete diagnosis, and procedure/investigations. These results were discussed in a clinical governance meeting and a poster was made to disseminate the conclusion and improve the quality of the discharge summary. Conclusions A total of £38,760 of funding was lost due to discrepancies in the clinical coding. An intervention in the form of a poster and teaching session was conducted for junior doctors and a repeat cycle is planned in the due course of time to improve the quality and minimise the loss of funding.

Study on the consistency between CBCT image features of sphenopalatine foramen and those seen in nasal endoscopy

Objective:To study the clinical anatomy of the sphenopalatine foramina by dissecting the sphenopalatine foramina during Vidian nerve branch neurotomy. The anatomy and CBCT images of sphenopalatine foramen were analyzed to facilitate the navigational of clinical operation using CBCT images. Methods:From October 2017 to September 2023, 84 cases（168 sides） of Vidian nerve branch neurotomy in our department were collected. The clinical summary was made according to the anatomy of sphenopalatine foramen during the operation. Preoperative CBCT imaging findings of the sphenopalatine foramina were also studied. Results:The clinical anatomy of sphenopalatine foramen could be divided into four types: middle meatus type（1.19%）, trans-meatus type（62.29%）, superior meatus type（33.33%） and double foramen type（1.19%）. The incidence of ethmoidal ridge was 98.81%. The distance from sphenopalatine foramina to posterior nasal canal were（14.63±2.66） mm to left and（14.65±2.63） mm to right, The position Angle ∠a of lower margin of sphenopalatine foramina were（62.36±10.05）° to left and（61.51±11.82）° to right, respectively. Axial CT images can be used to divide the sphenopalatine foramen into five levels: the upper edge of the sphenopalatine foramen level, the Vidian nerve level, the basal plate interaction level, the lower edge of the sphenopalatine foramen level and the pterygopalatine canal level. The agreement between endoscopic anatomy of sphenopalatine foramen and imaging navigation was 100%. Conclusion:The sphenopalatine foramina exhibit various anatomical types. The preoperative navigational CBCT reading can effectively identify the type of sphenopalatine foramina, guide the choice of surgical method, and help avoid serious complications. This has significant clinical application value.

The effect of SGLT2 inhibitors on health status in patients with heart failure: a systematic review and meta-analysis

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to improve health status in patients with heart failure (HF). We aim to evaluate the effect of SGLT2i on health status [by Kansas City Cardiomyopathy Questionnaire (KCCQ)] and if effect varied by ejection fraction (EF). Randomized clinical trials of SGLT2i in patients with HF till November 2022 were assessed. Change in KCCQ total symptom score (TSS), clinical summary score (CSS), and overall summary score (OSS) from baseline to 12-16 weeks, 32 weeks, and 52 weeks follow-up were assessed. Weighted mean differences (MD) in scores and odds ratios (OR) were pooled using a random-effects model. Twelve trials (n=23,679) were included. SGLT2i significantly improved KCCQ-TSS at 12-16 weeks [MD 2.16 (1.67, 2.65); p&lt;0.001], 32 weeks [MD 1.98 (1.43, 2.54); p&lt;0.001] and 52 weeks [MD 1.94 (1.19, 2.69); p&lt;0.001] follow-up. At 12-16 weeks, patients treated with SGLT2i had significantly higher odds of KCCQ-TSS improvement by ≥5 points [OR 1.27 (1.16, 1.39); p&lt;0.001], ≥10 points [OR 1.21 (1.11, 1.32); p&lt;0.001] and ≥15 points [OR 1.23 (1.14, 1.33); p&lt;0.001]. Similar results were observed at mid- and long-term follow-up, and for CSS and OSS. For all analyses, findings were consistent between patients with HF with reduced or preserved EF, acute/worsening or chronic HF, and which SGLT2i used (p-interaction &gt;0.20 for all). SGLT2i improve health status in patients with HF, with consistent and sustained benefits across all summary scores and HF subtypes. Treatment benefits were apparent within months of initiation and sustained to at least 1 year.

Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials

BackgroundMore women than men have heart failure with preserved ejection fraction (HFpEF). ObjectivesThe purpose of this study was to assess baseline characteristics and treatment effect of semaglutide by sex across the STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) program. MethodsIn a prespecified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes), patients with heart failure (HF), left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to once-weekly semaglutide 2.4 mg or matched placebo for 52 weeks. Dual primary endpoints (KCCQ-CSS change and percentage change in body weight) and confirmatory secondary endpoints (6-minute walking distance [6MWD] change; hierarchical composite endpoint comprising all-cause death, HF events, changes in KCCQ-CSS, and 6MWD; and C-reactive protein) were compared between sexes. ResultsOf 1,145 patients, 570 (49.7%) were women. Women had higher body mass index, left ventricular ejection fraction, C-reactive protein, and worse HF symptoms, and were less likely to have atrial fibrillation or coronary artery disease vs men. Semaglutide improved KCCQ-CSS regardless of sex (mean difference in women +7.6 points [95% CI: 4.5-10.7 points]; men +7.5 points [95% CI: 4.3-10.6 points]; P interaction = 0.94) but reduced body weight more in women (mean difference in women −9.6% [95% CI: −10.9% to −8.4%]; men −7.2% [95% CI: −8.4% to −6.0%]; P interaction = 0.006). Semaglutide improved 6MWD (P interaction = 0.21) and the hierarchical composite endpoint (P interaction = 0.66) in both sexes. Fewer serious adverse events were reported with semaglutide vs placebo. ConclusionsIn patients with obesity-related HFpEF, semaglutide 2.4 mg reduced body weight to a greater extent in women, and produced similar improvements in HF-related symptoms, physical limitations, and exercise function, regardless of sex. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511; and Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM]; NCT04916470)

Translation and Cross-Cultural Adaptation, Reliability and Validation Study of the Persian Version of Kansas City Cardiomyopathy Questionnaire

The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been developed to measure the health status of Congestive heart failure (CHF) patients. This study aimed to translate KCCQ into a Persian version and assess its validity and reliability. We used a forward-backward procedure to translate the questionnaire. In a cross-sectional study, 150 CHF patients and 50 healthy subjects over 30 years old were selected to assess the reliability and construct validity of the instrument. The face and content validity were used for the questionnaire's validity. The validity was examined on a population of patients with CHF using the Persian version of the Minnesota Living Heart Failure Questionnaire (MLHF) health survey. Calculation of the Intraclass correlation coefficient (ICC) and Cronbach's alpha was done to evaluate the questionnaire's reliability. Test-retest reliability was examined by re-administering the KCCQ after 2 weeks. Test-retest results demonstrated that the Persian version has excellent reliability (ICC for all domains was higher than 0.93, P≤0.000). Internal consistency was found by Cronbach's alpha to be 0.86 for the clinical summary and 0.87 for the overall summary, respectively. Also, the correlation between the components of KCCQ and MLHQ showed satisfactory construct validity. Good Pearson's Correlation Coefficient was seen between KCCQ and MLHF (r= -0.44, P≤0.000 for the clinical summary; r= -0.45, P≤0.000 for the overall summary). Analysing the data from 50 healthy persons and 150 patients were shown that the Persian version of KCCQ has acceptable discriminate validity for all domains except self-efficacy. The Persian version of the KCCQ had satisfactory reliability and validity for assessing health-related quality of life status for Iranian CHF patients.

AI-assisted clinical summary and treatment planning for cancer care: A comparative study of human vs. AI-based approaches.

1523 Background: Understanding a patient's clinical narrative, timeline, and history is critical for accurate treatment decision-making. However, reviewing and summarizing complex records is time-consuming and error-prone. Recent advancements in artificial intelligence (AI), specifically large language models (LLM), offer paths to improve quality and efficiency. Methods: A study was conducted on 50 breast cancer cases from an academic medical institution, utilizing all medical records—clinic, pathology, and radiology reports—up until the point of the initial treatment decision. All cases were processed using three different approaches: AI-assisted; full-AI; and human-only. In the AI-assisted method, two oncology physician assistants (PAs) revised AI-generated summaries to create clinical summaries. The full-AI method had AI independently produce clinical summaries, while the human-only method had the PAs compile summaries without AI. Eight board-certified international oncology specialists blindly evaluated summaries for faithfulness, completeness, and succinctness using a 3-point scale, ranked their preferences, and tried to predict which summaries were full-AI. Rankings were assessed using a Friedman test followed by a Wilcoxon signed-rank test, and full-AI prediction was assessed using a two-sided one-sample binomial test. After summarization, a distinct AI system with access to clinical guidelines provided treatment plans. These plans were then evaluated by a board-certified oncologist with access to the original treatment decision. Results: The study found specialists favored AI-assisted, followed by full-AI, and then human-only summaries, with average ranks of 1.73, 1.93, 2.34 respectively (lower is better, p&lt;0.001). The difference between full-AI and AI-assisted was not significant (p=0.11). Evaluation scores (mean±95%CI, higher is better) showed AI-assisted, full-AI, and human-only scored 2.35±0.13, 2.14±0.14, 2.17±0.14 for faithfulness; 2.28±0.12, 2.01±0.12, 1.93±0.14 for completeness; and 2.33±0.12, 2.21±0.12, 1.99±0.13 for succinctness. The average summarization time was 19.71, 1.17, 26.03 minutes. Full-AI identification accuracy was 0.28 (not different from chance 0.33, p=0.46). With AI-assisted summaries, the treatment plans were accurate in 45 cases (90%) and partially accurate in 5 cases (10%). In the 5 partially accurate cases, the system was accurate with the provided input data, but there were inaccuracies with the input data, including incorrect formats or missing data. Conclusions: Incorporating LLMs into the creation of medical summaries has shown improvements in both quality and efficiency, achieving up to 22.2x speed up with full-AI, indicating that AI-assisted summarization tools can potentially enhance care quality. AI-assisted summaries yield accurate treatment plans when the input data is accurate.

Evaluation of mavacamten in patients with hypertrophic cardiomyopathy.

We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients. A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated. We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN. Mavacamten demonstrated significant efficacy in reducing the postexercise LVOT gradient by 49.44 mmHg ( P = 0.0001) and LVEF by 3.84 ( P < 0.0001) and improving pVO 2 by 0.69 ml/kg/min ( P = 0.4547), KCCQ CSS by 8.11 points ( P < 0.0001), and patients with at least one NYHA functional class improvement from baseline by 2.20 times ( P < 0.0001). Importantly, mavacamten increased 1.11-fold adverse events ( P = 0.0184) 4.24-fold reduced LVEF to less than 50% ( P = 0.0233) and 1.06-fold SAEs ( P = 0.8631). Additionally, mavacamten decreased NT-proBNP by 528.62 ng/l ( P < 0.0001) and cTnI by 8.28 ng/l ( P < 0.0001). Mavacamten demonstrates both safety and efficacy in patients with HCM, suggesting its potential as a promising therapeutic strategy for this condition. Further research is warranted to confirm these results and explore its long-term effects.

The quality of reporting in case reports of permanent neonatal diabetes mellitus: a cross-sectional study

BackgroundAlthough randomized trials and systematic reviews provide the best evidence to guide medical practice, many permanent neonatal diabetes mellitus (PNDM) studies have been published as case reports. However, the quality of these studies has not been assessed. The purpose of this study was to assess the extent to which the current case reports for PNDM comply with the Case Report (CARE) guidelines and to explore variables associated with the reporting.MethodSix English and four Chinese databases were searched from their inception to December 2022 for PNDM case reports. The 23 items CARE checklist was used to measure reporting quality. Primary outcome was the adherence rate of each CARE item and second outcome was total reporting score for each included PNDM case report. Linear and logistic regression analyses were used to examine the connection between five pre-specified predictor variables and the reporting quality. The predictor variables were impact factor of the published journal (<3.4 vs. ≥3.4, categorized according to the median), funding (yes vs. no), language (English vs. other language), published journal type (general vs. special) and year of publication (>2013 vs. ≤ 2013).ResultIn total, 105 PNDM case reports were included in this study. None of the 105 PNDM case reports fulfilled all 23 items of the CARE checklist. The response rate of 11 items were under 50%, including prognostic characteristics presentation (0%), patient perspective interpretation (0%), diagnostic challenges statement (2.9%), clinical course summary (21.0%), diagnostic reasoning statement (22.9%), title identification (24.8%), case presentation (33.3%), disease history description (34.3%), strengths and limitations explanation (41.0%), informed consent statement (45.7%), and lesson elucidation (47.6%). This study identified that the PNDM case reports published in higher impact factor journals were statistically associated with a higher reporting quality.ConclusionThe reporting of case reports for PNDM is generally poor. As a result, this information may be misleading to providers, and the clinical applications may be detrimental to patient care. To improve reporting quality, journals should encourage strict adherence to the CARE guidelines.

Semaglutide and NT-proBNP in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program

BackgroundThe glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. ObjectivesThis study sought to determine if semaglutide 2.4 mg reduced N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with obesity-related HFpEF and compare treatment responses by baseline NT-proBNP. MethodsThis was a prespecified secondary analysis of pooled data from 2 double-blind, placebo-controlled, randomized trials (STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes]) testing effects of semaglutide in patients with obesity-related HFpEF. The main outcomes were change in NT-proBNP at 52 weeks and change in the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and body weight by baseline NT-proBNP. ResultsIn total, 1,145 patients were randomized. Semaglutide compared with placebo reduced NT-proBNP at 52 weeks (estimated treatment ratio: 0.82; 95% CI: 0.74-0.91; P = 0.0002). Improvements in health status were more pronounced in those with higher vs lower baseline NT-proBNP (estimated difference: tertile 1: 4.5 points, 95% CI: 0.8–8.2; tertile 2: 6.2 points, 95% CI: 2.4-10.0; tertile 3: 11.9 points, 95% CI: 8.1-15.7; P interaction = 0.02; baseline NT-proBNP as a continuous variable: P interaction = 0.004). Reductions in body weight were consistent across baseline NT-proBNP levels (P interaction = 0.21). ConclusionsIn patients with obesity-related HFpEF, semaglutide reduced NT-proBNP. Participants with higher baseline NT-proBNP had a similar degree of weight loss but experienced larger reductions in HF-related symptoms and physical limitations with semaglutide than those with lower NT-proBNP.

Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.

In the STEP-HFpEF trial programme, treatment with semaglutide resulted in multiple beneficial effects in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Efficacy may vary according to baseline diuretic use, and semaglutide treatment could modify diuretic dose. In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks, we examined whether efficacy and safety endpoints differed by baseline diuretic use, as well as the effect of semaglutide on loop diuretic use and dose changes over the 52-week treatment period. At baseline, across no diuretic (n = 220), non-loop diuretic only (n = 223), and loop diuretic [<40 (n = 219), 40 (n = 309), and >40 (n = 174) mg/day furosemide equivalents] groups, there was progressively higher prevalence of hypertension and atrial fibrillation; and greater severity of obesity and heart failure. Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from -8.8% [95% confidence interval (CI) -10.3, -6.3] to -6.9% [95% CI -9.1, -4.7] from no diuretics to the highest loop diuretic dose category; interaction P = .39). Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042). Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6 min walk distance) across diuretic subgroups (interaction P = .24-.92). Safety also favoured semaglutide vs. placebo across the diuretic subgroups. From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P < .0001). Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P < .001 for both) from baseline to 52 weeks. In patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide vs. placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks. NCT04788511 and NCT04916470.

Post-ICU psychology support during the COVID-19 pandemic.

Critical illness survival rates have improved, but patients frequently face prolonged new or worsened physical, cognitive and psychosocial impairments. These difficulties associated with critical care admission are known as post-intensive care syndrome (PICS). The multidisciplinary Intensive care Syndrome: Promoting Independence and Return to Employment (InS:PIRE) programme was developed to support patients in the recovery period from critical illness. During the COVID-19 pandemic, the psychology support offered by this service was adapted from an in-person group to individual remote review. This audit evaluated both the extent to which this input aligned with the recommended guidelines and the acceptability of this adapted delivery to this patient group, which could help guide post-pandemic psychology input to the service. The records of 207 patients were analysed retrospectively. The nature of support offered to a sub-sample of 50 patients detailed in clinical summary letters was compared with the Faculty of Intensive Care Medicine (2019) guidelines. Telephone calls were made to gather feedback on the virtual psychology support from 10 patients. Psychological difficulties were identified by 111 of the 207 patients who attended the virtual clinic. A total of 88 of these patients accepted referral for virtual psychology support and 67 (76%) of those patients attended. The virtual psychology support offered was found to be largely in accordance with ICU aftercare guidance and acceptable to patients. Patients found the summary letters of consultations accurate and helpful. Most patients expressed a preference for in-person support and the opportunity to meet other patients. The adaptations to the psychology support offered by InS:PIRE during the COVID-19 pandemic were found to be largely in line with ICU aftercare psychology guidelines and were acceptable to patients. Further research is needed on future methods of delivering psychology support for this patient group. This audit highlights issues important to patients in the post-ICU period based on individual consultations not previously possible. Patient opinion was sought on the impact of changing the delivery of post-ICU psychological support, which will help guide future improvements in the service.

Progress in the Study of Temporomandibular Joint Lavage in Temporomandibular Joint Disorder.

With the continuous development and progress of medicine, there are many methods for the treatment of temporomandibular disorders, among which temporomandibular joint lavage is also constantly developed. In the past century, through the efforts of some scholars and clinical summary, the understanding of this disease has been deepened and broadened. At present, through continuous exploration of the treatment methods, the lavage is relatively mature, and has achieved good clinical results. In this paper, the application of temporomandibular joint lavage in the treatment of temporomandibular joint disorders, its treatment methods, treatment mechanism, the auxiliary of other drugs, indications, complications and so on were discussed.

Safety and Efficacy of Metabolic Modulation With Ninerafaxstat in Patients With Nonobstructive Hypertrophic Cardiomyopathy

BackgroundIn nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics. ObjectivesThis study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM. MethodsPatients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints. ResultsA total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better VE/Vco2 (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of −2.1 (95% CI: −3.6 to −0.6; P = 0.006), with no significant difference in peak VO2 (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: −2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; P = 0.04). ConclusionsIn symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a phase 3 study.

SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure

The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported. To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF. The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023. Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included. Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted. Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS). In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes. These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.