Eligible Patients Research Articles

Effect of the National Enhanced Service for weight management on the content of annual review consultations for patients living with obesity and hypertension and/or diabetes.

Guidelines specify that clinicians should support patients living with obesity by referring to weight management programmes (WMPs), but clinicians do so infrequently. To provide additional support to patients living with obesity and weight-related conditions, the UK government instated the National Enhanced Service (NES) for weight management in England, including a reimbursement to general practices for referring eligible patients to WMPs. To assess the impact of the NES on conversations regarding weight and relevant behavioural risk factors in primary care consultations we recruited 11 medical practices in England where the NES was operating and six comparator practices from Scotland and Wales where the NES was not implemented. Clinicians audio-recorded annual review appointments of patients living with obesity and hypertension and/or diabetes. The content of these consultations was synthesised using quantitative content analysis. Consultations with 92 patients were analysed: 58 in England and 34 in Scotland and Wales. No difference was found between the NES sites (England) and non-NES sites (Scotland and Wales) in the proportion of referrals made to WMPs. Clinicians in England weighed patients and took other body measurements more often, mentioned body mass index more often, and had more detailed discussions about patients' diets, but there was no evidence that they differed in their discussion of WMPs or other modifiable risk factors. We found no strong evidence that the NES affected how clinicians addressed weight management or related behavioural risk factors within annual review consultations for patients living with obesity and hypertension and/or diabetes.

Collagenase Chemonucleolysis for Treating Cervical Disc Herniation: An Exploratory, Single-Arm, Open-Label, Multicenter Clinical Trial.

Cervical disc herniation (CDH) is the most common cause of cervical radiculopathy and causes persistent neck pain and neurological deficits. Collagenase chemonucleolysis has been successfully applied to treat lumbar disc herniation, which has a similar pathological mechanism to CDH. However, its application for CDH remains under-researched, and there is an even greater lack of high-quality clinical evidence. This study aims to evaluate the efficacy and safety of collagenase chemonucleolysis for treating CDH. Eligible patients with CDH underwent collagenase chemonucleolysis via anterior cervical intradiscal injection or epidural injection. The primary efficacy endpoint showed an excellent and good rate regarding the Odom criteria, which was not lower than the reference value (≥ 78%) at 6 months postoperatively. The secondary efficacy endpoints were the percentage reduction in Numeric Rating Scale (NRS) and Neck Disability Index (NDI) scores from baseline, which were not lower than the reference values (≥ 40%, ≥ 30%), and improvement in the 36-Item Short Form Health Survey (SF-36) score compared to the preoperative value. The pre- and postoperative CDH index of patients were also compared. Safety endpoints included the incidence of adverse events (AEs) and serious adverse events (SAEs). An excellent and good rate regarding the Odom criteria 6 months postoperatively was 90.5% (133/147), which was significantly higher than 78% (P < 0.004, 95% confidence interval 85.7-95.2%). The reduction in NRS and NDI scores exceeded 40% (P < 0.001) and 30% (P < 0.001), respectively. The SF-36 scores at 3 months and 6 months postoperatively were significantly higher than those preoperatively (P < 0.001). A significant difference was observed in the pre- and postoperative CDH index (109.6 ± 119.1 vs. 70.8 ± 74.8, P < 0.001). The incidence of AEs was 22.5% (33/147), of which 97.8% were grade 1-2. No collagenase-related AEs and SAEs occurred. Collagenase chemonucleolysis treatment for CDH exhibited favorable efficacy and safety and may be a better choice for patients in whom conservative treatment is ineffective. The trial was registered on www.Chictr.org.cn (ChiCTR2200063043).

Feasibility and acceptability of the brief patient-reported experience measure consideRATE within the hospital setting for patients with palliative care needs, their families/carers and clinicians.

Supporting clinical teams to improve care for inpatients with palliative care needs and their carers is a known priority. Patient reported experience measures (PREMs) may assist in improvement work. Evidence about how to collect and feedback PREM data for this population and context is required. To determine the feasibility of implementing a brief, validated PREM, consideRATE and appraise its acceptability as perceived by inpatients with palliative care needs, their carers and clinicians. A prospective study using: 1) PREM administration, screening log and field note completion; and; 2) a focus group with clinicians. Eligible participants recruited from three wards (cancer care and internal medicine) of an Australian tertiary metropolitan hospital. Participants included patients screened to have palliative care needs (using the SPICTTM criteria), their carers and multidisciplinary clinicians (including clinical managers). Feasibility: A 71% response rate was achieved (n = 80 from 112 eligible patients approached). Mean screening time to inform eligible patients for PREM completion was 7.5 min. More than half of eligible participants (n = 47, 59%) opted for electronic completion of consideRATE and mean completion time was 6.12 min. A third of participants required assistance for PREM completion (n = 27, 34%). Score distribution varied across response options, albeit with a positive skew towards 'very good' and 'good'. Two thirds of respondents (n = 50, 62.5%) provided ⩾1 free-text response. Acceptability: Clinicians valued consideRATE data noting feedback needed to be: accessible, supported by free-text and responsive to local contexts. It is feasible to implement consideRATE for inpatients with palliative care needs. Clinicians note consideRATE data is acceptable in informing improvement foci.

First-line benmelstobart plus anlotinib and chemotherapy in advanced or metastatic/recurrent esophageal squamous cell carcinoma: a multi-center phase 2 study

Although first-line immunochemotherapy has improved prognosis for patients with advanced esophageal squamous cell carcinoma (ESCC), more effective strategies still require further investigation. This multi-center, phase II study (ClinicalTrials.gov NCT05013697) assessed the feasibility of benmelstobart (a novel PD-L1 inhibitor) plus anlotinib (multitargeted TKI) and chemotherapy in advanced or metastatic/recurrent ESCC. Eligible patients received 4–6 cycles (21-day) of benmelstobart (1200 mg), anlotinib (10 mg) plus paclitaxel (135 mg/m2)/cisplatin (60–75 mg/m2), then maintained with benmelstobart and anlotinib. Primary endpoint was progression-free survival (PFS) assessed according to RECIST v1.1. Secondary endpoints were tumor response, overall survival (OS), and safety assessed by adverse events (AEs). From September 2021 to November 2023, 50 patients were enrolled and received study treatment. With median follow-up of 23.7 months as of April 1, 2024, median PFS was 14.9 months (95% CI, 11.4-not estimable [NE]) and the 1-year PFS was 58.5% (95% CI, 41.9%–71.9%). Among 50 patients, confirmed objective response rate was 72.0% and disease control rate was 84.0%. Median duration of response of 36 responders was 16.2 months (95% CI, 10.2-NE). At the cutoff date, 31 patients remained alive; median OS was not reached (95% CI, 13.2 months-NE) with 1-year OS of 74.8% (95% CI, 59.8%–84.8%). Forty-six (92.0%) patients reported treatment-related AEs, with 37 (74.0%) were grade ≥3. Overall, benmelstobart plus anlotinib and chemotherapy showed promising efficacy and acceptable toxicity in advanced or metastatic/recurrent ESCC.

Effect of Minimally Invasive Gastrectomy on Return to Intended Oncologic Therapy for Gastric Cancer.

Adjuvant chemotherapy offers survival benefit to patients with gastric cancer. Only 50-65% of patients who undergo neoadjuvant chemotherapy and gastrectomy are able to receive adjuvant therapy. It is optimal to start adjuvant therapy within 8weeks after gastrectomy. We compared the rate of return to intended oncologic therapy (RIOT) between minimally invasive gastrectomy (MIG) and open gastrectomy (OG). Retrospectively, we analyzed patients who underwent gastrectomy within a multi-hospital university-based health system (2019-2022). Data on patient demographics, comorbid conditions, operative approach, and postoperative outcomes were assessed with univariate analysis and multivariable analysis (MVA) to determine the association with RIOT. Among 87 eligible patients, 33 underwent MIG and 54 underwent OG. There were no differences in demographics, performance status, comorbid conditions, or type of gastrectomy between the two groups. MIG patients were significantly more likely to RIOT compared with OG patients (87.9% vs. 63%, p=0.003), with 73.1% of MIG patients starting adjuvant therapy within 8weeks compared with 53.1% of OG patients. Factors associated with higher odds of RIOT included MIG and age <65years, while major postoperative complications (Clavien-Dindo grade ≥IIIa) was associated with lower odds of RIOT. On MVA, MIG was independently associated with higher odds of RIOT compared with OG (odds ratio 6.05, 95% confidence interval 1.47-24.78, p=0.008). The minimally invasive approach may benefit patients undergoing gastrectomy, irrespective of the extent of gastric resection for adenocarcinoma. MIG is associated with a higher likelihood of (1) RIOT and (2) starting adjuvant therapy within the optimal time period after gastrectomy.

Resuscitation of adult shocked trauma patients using major haemorrhage protocol guided by viscoelastic haemostatic assays versus formulaic approach.

The resuscitation of trauma patients with critical bleeding may follow a formulaic approach using high ratios of blood components or a viscoelastic haemostatic assay (VHA) guided approach. The aim of this study was to compare the two strategies for resuscitation of shocked trauma patients. This was a registry-based cohort study including shocked trauma patients from two trauma centres-one practising a formulaic approach, with VHA unavailable during trauma resuscitation and the other practicing a VHA-guided resuscitation strategy. The primary outcome was the total units of blood components transfused in 24 h after adjusting for differences in baseline characteristics and time to death. Between 01 Jan 2020 and 31 Dec 2022, 152 eligible patients were categorised to the formulaic group and 40 to the VHA group. Prehospital times were longer in the formulaic group (2.0 vs. 1.4 h), and more patients in the VHA group (38% vs. 17%) were transfused prehospital blood components. Formulaic resuscitation was associated with significantly more blood components transfused (adjusted incidence rate ratio 1.5; 95%CI: 1.4-1.7, p < 0.001). Using a formulaic approach, patients were administered more red blood cells, plasma and platelets, but fewer cryoprecipitate. There was no significant association of the formulaic approach with in-hospital mortality (adjusted odds ratio 2.4; 95%CI: 0.7-8.0, p = 0.17). Given the cost and potential adverse effects of blood component transfusions, VHA-guided transfusion strategies present an attractive option, particularly among centres managing high volumes of shocked patients. Further trials, enrolling the population most likely to benefit from precision transfusion strategies, are indicated.

Magnetic resonance elastography is useful to determine the severity of liver fibrosis according to liver biopsy in post-fontan patients.

The reliability of various modalities for assessing and monitoring Fontan-associated liver disease compared to liver biopsy remains an intriguing subject of inquiry. Our objective was to assess the efficacy of multiple modalities in comparison to liver histology for evaluating liver fibrosis in post-Fontan patients. We conducted a cross-sectional study involving Fontan patients without known liver disease. Eligible patients underwent cardiac and hepatic evaluations, including ultrasound liver elastography, magnetic resonance elastography (MRE) of the liver, computerized tomography (CT) scan of the upper abdomen, echocardiography, cardiac catheterization, and liver biopsy. The severity of liver fibrosis was categorized using the METAVIR score derived from liver biopsy results: F0/F1 indicated no or mild fibrosis, F2 indicated significant fibrosis, F3 indicated advanced fibrosis and F4 indicated cirrhosis. A total of 38 patients (mean age 21 ± 6.5 years, 52.6% female) were included in the cross-sectional study, with a mean time elapsed since the Fontan operation of 13 years. Parameters obtained from echocardiography, ultrasound liver elastography, and CT scan of the upper abdomen did not exhibit significant differences among the groups. Notably, liver biopsy revealed advanced cirrhosis in 23 out of 38 patients and none were diagnosed with hepatocellular carcinoma. Multivariate logistic regression analysis demonstrated that the factor significantly associated with significant liver fibrosis or cirrhosis in post-Fontan patients was liver stiffness with MRE > 4.4kPa [OR 13.5 (95% CI 1.2-152.2)]. Our findings suggest that post-Fontan patients with liver stiffness of MRE > 4.4kPa should undergo further investigation. These results contribute to understanding the liver fibrosis assessment in post-Fontan patients and highlight the importance of MRE in predicting significant liver disease.

Effects of a structured, family-supported, and patient-centred advance care planning on end-of-life decision making among palliative care patients and their family members: protocol of a randomised controlled trial

BackgroundAdvance care planning (ACP) is a well-recognized quality indicator for palliative care. Despite two decades of effort, previous studies showed that ACP-related documentation and end-of-life discussion rates remain low for palliative care patients. Although ACP is about self-determination and autonomy, studies consistently show the importance of family involvement in adult patient’s medical decision-making. Yet, research on ACP interventions with structured components targeting family member remained limited. The current study aims to evaluate the effectiveness of a structured, family-supported, patient-centred ACP programme for adult palliative care patients and their families.MethodsThis is a 2-arm parallel group randomized controlled trial with follow-ups at 6 and 12 months. One hundred and seventy eligible palliative care patients and their families are planned to be recruited from three hospitals, and randomized to either a structured, family-supported, patient-centred ACP programme (ACP-Family) or usual ACP care (ACP-UC) arm. The ACP-Family intervention consists of 2 sessions. The primary outcome is family’s prediction accuracy of patient’s treatment preferences at 6 months. Secondary outcomes include proportions of new ACP documentations and family-reported perception of whether the patient’s end-of-life (EOL) care preference was respected; patient’s decisional conflict; quality of communication; family’s decision-making confidence; family’s anxiety and depression; and patients’ and family members’ satisfaction of the intervention. Outcomes of the two groups will be compared using regressions and linear mixed-effects models.DiscussionThis study will provide rigorous scientific evidence on the effectiveness of a structured and well-design family-supported, patient-centred ACP programme for adult palliative care patients and their family members in the hospital setting. If the ACP-Family proves to be effective, it will provide a structured and systematic approach to facilitate ACP discussions involving family members. This will respond to local needs and inform international ACP practice.Trial registrationClinicalTrials.gov Identifier: NCT05935540.

Comparison of clinical characteristics and outcomes between COVID-19 survivors and non-survivors: a retrospective observational study

Background To compare the clinical characteristics of COVID-19 survivors and non-survivors who were transferred from general wards to the critical care units in four tertiary hospitals of Nepal. Methods This study utilized electronic data from the National Intensive Care Unit (ICU) registry managed by the Nepal Intensive Care Research Foundation (NICRF). A retrospective observational study was conducted among 78 eligible COVID-19 patients admitted to the intensive care units of four different hospitals between 2020 and 2022. The Mann-Whitney U test was used to compare each continuous variable between the survivors and non survivors, while Pearson's chi-squared test was used to examine the association between each categorical variable and outcome. Results Among 78 cases of COVID-19 studied, 29 (37.1%) had died, and 49 (62.8%) had recovered. The median age of the patient was 57.5 years, with a higher percentage of males (66.6%). Hypertension (41%) and diabetes (26.9%) were common comorbidities, whereas pneumonia (41%) and acute respiratory distress syndrome (19.2%) were common complications. Most patients required oxygen therapy (96.2%). Corticosteroids (76.9%) and anticoagulants (83.3%) were commonly administered medications. Median of mean arterial pressure was 85 mm Hg [ IQR- 79.2 - 99.5] in non-survivors and 93.3 mm Hg [IQR- 86.6 - 102.6 ] in survivors which was significantly different between the two groups (p=0.04). Nine of the patients had cardiac dysfunction on ICU admission, of which none survived (p=0.001). Out of ten patients requiring inotropes or vasopressors, only two survived (p=0.001). Conclusions Non-survivor COVID patients had lower mean arterial pressure on admission to intensive care units. A higher proportion of patients with cardiac dysfunction and requiring inotropes or vasopressors could not survive.

Evaluating the influence of parental atopy on the effectiveness of a maternal dairy-free diet in alleviating infantile colic: a before-and-after study

BackgroundInfantile Colic (IC) poses a significant challenge for parents as it manifests through repeated and extended episodes of fussiness, crying, or irritability occurring before the age of 5 months. The precise cause of IC is currently unknown. The association between IC, a family history of atopy, and the development of individual atopy in the future remains uncertain, given conflicting findings from prior studies.ObjectivesThis study aimed to investigate the impact of parental atopy on IC severity and the effectiveness of the mother’s hypoallergenic Dairy-Free Diet in alleviating pain in infants with colic.MethodsThis non-randomized trial conducted at Amirkabir Hospital in Arak, Iran, from January 2023 to October 2023, involving 206 eligible IC patients non-randomly assigned to two groups based on parental atopy history. Breastfed infants were prescribed a dairy-free diet, involving the removal of dairy products from the mother’s diet. Pain severity was assessed using the FLACC scale at baseline and after one-month of intervention.ResultsThe research initially involved 206 subjects with an average age of 28.77 ± 9.99 days, evenly distributed based on parental atopy history. However, there was a 28.6% loss to follow-up, resulting in a final analyzed population of 147 individuals. The intervention, a maternal dairy-free diet, demonstrated a significant reduction in pain symptoms within both groups and overall (P = 0.001), with no significant difference in efficacy between infants with and without parental atopy history (P = 0.219). Parental history of atopy did not exhibit a significant association with colic pain severity (P = 0.404). The study revealed that the impact of the diet on colic severity varied, with more pronounced effects observed in cases of severe and moderate colic compared to mild cases.ConclusionsAdopting a Dairy-Free Diet significantly reduced colic symptoms, irrespective of parental atopy history. The severity of colic appears unrelated to parental atopy, and the observed improvement with a Dairy-Free diet is potentially attributed to milk intolerance rather than milk allergy.

Association of commission on cancer accreditation with receipt of guideline-concordant care and survival among patients with colon cancer.

Guideline-concordant care (GCC) is associated with improved survival for patients with cancer; however, variations in receipt of GCC remain a concern. The objective of this study was to evaluate the association of Commission on Cancer (CoC) hospital accreditation status with receipt of GCC and survival among patients with colon cancer. This retrospective observational study identified patients diagnosed with stage I-IV colon cancer from 2018 to 2020 from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program Database. Guideline concordance was defined as receipt of stage-appropriate lymphadenectomy or chemotherapy. Multivariable logistic regression models investigated associations with receipt of GCC. Cox proportional hazards regression models assessed 3-year cancer-specific mortality risk. Of 222,583 patients with colon cancer, 146,629 (91.2%) of eligible patients received guideline-concordant lymphadenectomy and 70,586 (81.9%) of the eligible patients received guideline-concordant chemotherapy. Treatment at CoC-accredited hospitals was the strongest modifiable predictor for receipt of guideline-concordant lymphadenectomy (odds ratio [OR] 1.82; 95% confidence interval [CI] 1.75-1.88) and chemotherapy (OR 2.14; 95% CI 2.06-2.23). Among patients treated at CoC-accredited hospitals, risk adjusted mortality was decreased for patients with stage I-II disease (hazard ratio [HR] 0.94; 95% CI 0.80-0.99), stage III disease (HR 0.93; 95% CI 0.88-0.98), and stage IV disease (HR 0.88; 95% CI 0.84-0.92). For patients with colon cancer, treatment at CoC-accredited hospitals was associated with increased receipt of GCC and decreased mortality risk. Benchmarking data may serve as a valuable accountability tool for quality assessment to improve cancer treatment and outcomes.

Expanding Naloxone Coprescribing at a Regional VA Medical Center.

Veterans are disproportionately affected by chronic pain and are more likely to be prescribed opioids. As a means of risk mitigation, the Centers for Disease Control and Prevention and Department of Defense recommend naloxone for patients on opioids with risk factors, including use of ≥50 morphine milligram equivalents daily, concurrent benzodiazepine/sedative use, and pulmonary or liver disease. An interprofessional quality improvement team consisting of 6 residents, a pharmacist, a nurse educator, and a faculty mentor was formed to increase naloxone coprescriptions at a regional VA medical center Continuity of Care Clinic. Primary intervention identified eligible patients via the VA Primary Care Almanac's Opioid Therapy Risk Report and alerted providers by email and secure messaging. Naloxone coprescription rates increased from 42% initially in June 2022 to 82% by June 2023 (29/69 to 41/50 patients, P < 0.0001). This project demonstrates that notifying providers of high-risk patients can significantly increase naloxone coprescriptions.

Magnetic resonance imaging-guided single-fraction preoperative radiotherapy for early-stage breast cancer (the RICE trial): feasibility study

BackgroundOver the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer.MethodsThe RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac.The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI.ConclusionThe RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes.Trial registrationThis trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808.

Arsenic trioxide versus Realgar-Indigo naturalis formula in non-high-risk acute promyelocytic leukemia: a multicenter, randomized trial.

Realgar-Indigo Naturalis Formula (RIF) is an oral form of arsenic that is effective against acute promyelocytic leukemia (APL). This multicenter, randomized, controlled trial compared the efficacy of all-trans retinoic acid (ATRA) plus RIF with ATRA plus arsenic trioxide (ATO) in a simplified regimen for non-high-risk APL. Following induction therapy with ATRA and ATO, participants were randomly assigned to receive either ATRA plus ATO or ATRA plus RIF both in a 2-week on 2-week off schedule for consolidation therapy. Once achieving molecular complete remission, the regimen was administered for a total of 6 cycles. All of 108 eligible patients achieved hematological complete remission after induction therapy. The median follow-up time was 29 months. The primary endpoint of two-year disease-free survival was 97% in the ATRA-RIF arm and 98% in the ATRA-ATO arm, respectively. (The ATRA-RIF arm was found to be non-inferior to the ATRA-ATO arm, (P < .01), with a percentage difference of -1% (95%CI, -4.8 to 6.9). No deaths have been observed. Most adverse events were moderate. This study confirms the noninferiority of RIF to ATO for non-high-risk APL, while also offering a more favorable regimen schedule for post-remission therapy. (ClinicalTrials gov. Identifier: as NCT02899169).

Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized-trial.

Carvedilol is a non-selective β-blocker (NSBBs) with anti-α1-adrenergic activity, more effective than traditional NSBBs in reducing portal-pressure (HVPG). However, 35%-45% of patients still have insufficient HVPG-decrease. Statins ameliorate endothelial dysfunction, reduce hepatic vascular resistance, and have pleiotropic effects. We investigated whether the addition of simvastatin improves the efficacy of carvedilol on HVPG in cirrhosis with severe portal-hypertension and suboptimal response to traditional-NSBBs. Patients with cirrhosis and high-risk varices referred for primary prophylaxis were consecutively included. HVPG was measured at baseline and again after i.v.propranolol. Suboptimal responders (HVPG-decrease <20%) were treated with carvedilol and were randomized to double-blind administration of placebo or simvastatin. Chronic HVPG response was assessed after 4-6-weeks, repeating HVPG-measurements after a standard liquid meal to estimate endothelial dysfunction. Plasma samples were obtained before each study to investigate inflammatory parameters. Of 184 eligible patients, 82 were randomized to carvedilol+simvastatin (N=41) or carvedilol+placebo (N=41). Baseline characteristics were similar. HVPG significantly decreased with both, carvedilol+simvastatin (18.6±4-to-15.7±4mm Hg, p<0.001) and carvedilol+placebo (18.9±3-to-16.9±3mm Hg, p<0.001). The decrease was greater with carvedilol+simvastatin (2.97±2.5 vs. 2.05±1.6mm Hg, p=0.031). An HVPG-decrease ≥20% occurred in 37% versus 15% patients respectively (OR:3.37, 95% CI=1.15-9.85; p=0.021). With test-meal, HVPG increased in both groups (p<0.01), although carvedilol+simvastatin attenuated such increment (12±8% vs. 23±16%, p<0.001). Cytokine levels (IL-6,MCP-1,MDA) decreased significantly more with carvedilol+simvastatin (p<0.01). Incidence of adverse events was similar. In patients with severe portal hypertension (all with high-risk varices) and suboptimal hemodynamic response to traditional NSBBs, combined therapy with carvedilol plus simvastatin significantly enhances the portal-pressure reduction achieved with carvedilol-monotherapy, improves endothelial dysfunction and reduces pro-inflammatory cytokines.

Decision Support Intervention and Anticoagulation for Emergency Department Atrial Fibrillation

Oral anticoagulation for adults with atrial fibrillation or atrial flutter (AFF) who are at elevated stroke risk reduces the incidence of ischemic stroke but remains underused. Efforts to increase anticoagulation initiation on emergency department (ED) discharge have yielded conflicting results. To evaluate the effectiveness of a multipronged intervention supporting anticoagulation initiation for eligible adult ED patients. The Clinical Decision Support to Optimize Care of Patients With Atrial Fibrillation or Flutter in the Emergency Department (O'CAFÉ) pragmatic, stepped-wedge cluster randomized clinical trial was conducted from July 1, 2021, through April 30, 2023, at 13 community medical centers (in 9 clusters) of an integrated health system in Northern California. The study included adult ED patients with primary AFF eligible for anticoagulation initiation when discharged home. Clusters were randomly assigned to staggered dates for 1-way crossover from the control phase (usual care) to the intervention phase. Physician education, facility-specific audit and feedback, and access to decision support, which identified eligible patients and recommended shared decision-making, anticoagulation initiation (if suitable), and timely follow-up. The main outcome was a composite of anticoagulation on discharge or within 30 days. A primary intention-to-treat analysis (decision support access regardless of use) and a secondary per-protocol analysis (decision support use) were performed. Multivariable analyses adjusted for intervention and exposure months with random effects, accounting for clustering by facility and patient. A total of 3388 eligible patients with atrial fibrillation were discharged home: 2185 (64.5%) were receiving pre-ED arrival anticoagulation and 1203 (35.5%) were eligible for anticoagulation. Among the 1203 patients with an initiation-eligible encounter, the median age was 74.0 (IQR, 68.0-82.0) years and approximately half (618 [51.4%]) were men. Among the 387 patients with an initiation-eligible control encounter, 244 (63.0%) received anticoagulation (190 [49.0%] at discharge and 54 [14.0%] within 30 days). Among the 816 patients with an initiation-eligible intervention encounter, 558 (68.4%) received anticoagulation (428 [52.5%] on discharge and 130 [15.9%] within 30 days). There was no statistically significant change in initiation of anticoagulation associated with the intervention (adjusted odds ratio, 1.33 [95% CI, 0.75-2.35]; P = .13). Decision support was used for 217 eligible case patients (26.6%) (per protocol) and was associated with a statistically significant change in anticoagulation initiation when compared with 599 patients for whom decision support was not used (164 [75.6%] vs 394 [65.8%]; P = .008). In this trial, a multipronged intervention to facilitate thromboprophylaxis among eligible ED patients with AFF did not significantly increase anticoagulation initiation. Opportunities exist to further improve stroke prevention among ED patients with primary AFF. ClinicalTrials.gov Identifier: NCT05009225.

Compare three deep learning-based artificial intelligence models for classification of calcified lumbar disc herniation: a multicenter diagnostic study

ObjectiveTo develop and validate an artificial intelligence diagnostic model for identifying calcified lumbar disc herniation based on lateral lumbar magnetic resonance imaging(MRI).MethodsDuring the period from January 2019 to March 2024, patients meeting the inclusion criteria were collected. All patients had undergone both lumbar spine MRI and computed tomography(CT) examinations, with regions of interest (ROI) clearly marked on the lumbar sagittal MRI images. The participants were then divided into separate sets for training, testing, and external validation. Ultimately, we developed a deep learning model using the ResNet-34 algorithm model and evaluated its diagnostic efficacy.ResultsA total of 1,224 eligible patients were included in this study, consisting of 610 males and 614 females, with an average age of 53.34 ± 10.61 years. Notably, the test datasets displayed an impressive classification accuracy rate of 91.67%, whereas the external validation datasets achieved a classification accuracy rate of 88.76%. Among the test datasets, the ResNet34 model outperformed other models, yielding the highest area under the curve (AUC) of 0.96 (95% CI: 0.93, 0.99). Additionally, the ResNet34 model also exhibited superior performance in the external validation datasets, exhibiting an AUC of 0.88 (95% CI: 0.80, 0.93).ConclusionIn this study, we established a deep learning model with excellent performance in identifying calcified intervertebral discs, thereby offering a valuable and efficient diagnostic tool for clinical surgeons.

Revalidation of Proactive Gastrostomy Tube Placement Guidelines for Head and Neck Cancer Patients Receiving Helical Intensity-Modulated Radiotherapy

The Royal Brisbane and Women’s Hospital (RBWH) Swallowing and Nutrition Management Guidelines for Patients with Head and Neck Cancer were developed to enable evidence-based decision-making by the Head and Neck Multidisciplinary Team (H&amp;N MDT) regarding enteral nutrition support options. The purpose of this study was to revalidate these guidelines in a cohort of patients receiving helical intensity-modulated radiotherapy (H-IMRT) compared to a historical cohort who received primarily 3D-conformal radiotherapy. Eligible patients attending the RBWH H&amp;N MDT between 2013 and 2014 (n = 315) were assessed by the guidelines, with high-risk patients being recommended proactive gastrostomy tube placement. Data were collected on guideline adherence, gastrostomy tube insertions, the duration of enteral tube use and weight change. Sensitivity, specificity and positive predictive and negative predictive values were calculated and compared with the historical cohort. Overall guideline adherence was 84%, with 60% and 96% adherence to the high-risk and low-risk pathways, respectively. Seventy patients underwent proactive gastrostomy tube placement (n = 62 high-risk; n = 8 low-risk). Validation outcomes were sensitivity 73% (compared to 72%) and specificity 86% (compared to 96%). The guidelines yielded a high sensitivity and specificity, remaining valid in a cohort of patients treated with H-IMRT. Further studies are recommended to improve the sensitivity and understand the decrease in specificity in order to make ongoing guideline improvements.

Inetetamab for injection in combination with vinorelbine weekly or every three weeks in HER2-positive metastatic breast cancer: A multicenter, randomized, phase II clinical trial.

We aimed to investigate the pharmacokinetics, safety, efficacy, and immunogenicity of different dosing regimens (weekly and every three weeks) of inetetamab in combination with vinorelbine in human epidermal growth factor receptor 2 (HER2)+ patients with metastatic breast cancer who had received one or more chemotherapy regimens. HER2+ patients with metastatic breast cancer who had received one or more chemotherapy regimens were included. Eligible patients received inetetamab administered weekly or every three weeks in combination with vinorelbine injection chemotherapy. Pharmacokinetics, safety, efficacy, and immunogenicity were compared between the groups. Sixty HER2+ patients were randomized into a single-week administration group ( n = 29) and a three-week administration group ( n = 31). After the final dose in the single-week administration group and the three-week administration group, the mean Cmax values were 79.773 μg/mL and 146.083 μg/mL; the mean Cmin values were 30.227 μg/mL and 11.926 μg/mL; the mean AUCtau values were 7328.443 μg·h/mL and 22647.101 μg·h/mL; and the mean Cav values were 43.622 μg/ mL and 44.935 μg/mL, respectively. The best overall response (BOR) rates at 24 weeks and unconfirmed BOR rates at 24 weeks were both 40.7% in the single-week dosing group and 40.7% in the three-week dosing group, and the 24-week confirmed disease control rates (DCRs) were 88.9% and 81.5%, respectively. The incidence of adverse events (AEs) was generally consistent across all levels. There were slight differences in the mean Cmax, Cmin, AUCtau and Cav between the three-week dosing group and the single-week dosing group, and the mean steady-state concentrations of Cav were comparable; however, there were no differences in efficacy, safety or immunogenicity between the two groups.

Pragmatic online obesity treatment in primary care: a hybrid randomized clinical trial of implementation strategies

Online behavioral weight loss (BWL) in primary care is effective and disseminable. This trial compared two implementation approaches on program uptake, use, and weight loss via a pragmatic hybrid type 2 implementation-effectiveness design to evaluate online BWL implementation (Rx Weight Loss [RxWL]) and effectiveness. This manuscript presents the implementation results. RxWL was implemented across a state-wide network of primary care clinics using lower- and higher-intensity implementation strategies (Basic [base program] and Enhanced [base plus enhanced training and dashboard], respectively) between 2018 and 2022. Nurse care managers (NCMs; N = 23) were recruited and block-randomized to implementation condition. Adult primary care patients (body mass index [BMI] > 25 kg/m2, internet-connected device access) were referred and enrolled by their NCMs. Outcomes were the proportion of eligible patients who enrolled in and completed RxWL by NCM condition, initial weight loss and regain over 12 and 24 months by NCM condition, and clinician acceptability and feasibility. NCMs (N = 12 Enhanced, N = 11 Basic) in Enhanced enrolled more patients (N = 490) than in Basic (N = 164). Although the proportion of patients who completed RxWL and mean weight loss did not differ by condition, different enrollment rates resulted in the Enhanced condition engaging more patients. NCMs rated RxWL as acceptable and feasible with no difference by condition. Findings support connecting primary care patients with technology-based health behavior change programs. Clinical trial registration number: ClinicalTrials.Gov identifier NCT03488212: https://clinicaltrials.gov/ct2/show/NCT03488212. Trial registration: clinicaltrials.gov Identifier: https://clinicaltrials.gov/study/NCT03488212.