Nonrandomized Study Research Articles

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort

BackgroundThere is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). MethodsThis retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. ResultsOf 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47–0.66, p < 0.001). ConclusionIn NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

디지털 헬스 프로그램이 국내 노인의 인지기능과 우울에 미치는 효과

Objectives This study is a systematic review and meta-analysis on the effects of a digital health intervention pro-gram applied to the elderly in Korea on cognitive function and depression. Methods For the meta-analysis, a total of 4,261 articles were searched using five domestic academic search da-tabases, RISS, NDSL, KISS, Kmbase, and DBpia, until January 11, 2024. The literature search targeted only aca-demic journal papers, and there was no limit to the search period. A total of 11 studies were included in the meta-analysis according to the data selection and exclusion criteria, and effect size and heterogeneity were ana-lyzed using the R 4.3.2 program. Results Among the 11 selected papers, 5 were randomized controlled experimental studies and 6 were non-randomized controlled studies, and the effect size of the digital health intervention program for the elderly in Korea on cognitive function was 0.30 (95% CI: -0.01~-0.60) ), which was a small effect size, and the effect size for depression of the digital health intervention program for the elderly in Korea was a large effect size of -0.80 (95% CI: -1.13~-0.47). Conclusions Based on the results of this study, the digital health intervention program was effective in improving cognitive function and reducing depression in the elderly. Based on this, the development of an intervention pro-gram effective in improving cognitive function and reducing depression and the basis for educational strategies using digital in university education It can be used as data.

Effects of virtual reality OSCE on nursing students’ education: a study protocol for systematic review and meta-analysis

IntroductionVirtual objective structured clinical examination (OSCE) has been shown to influence the performance of nursing students. However, its specific effects, particularly students’ competence, stress, anxiety, confidence, satisfaction with virtual reality...

An incremental energy stimulation test to predict success in left bundle branch capture

Abstract Introduction Left bundle branch (LBB) stimulation is guided by fluoroscopic projections and electrocardiographic criteria limited by positional variations. Purpose To evaluate an incremental energy stimulation test (IEST) to optimize success. Methods Prospective, non-randomized experimental study for proof-of-concept analysis (N=23), consisting on: (i) stimulation at three locations at the high, middle and low right mid-ventricular septum (right oblique 30o); and (ii) continuous unipolar stimulation (lumenless fixed helix electrode) at each location with increasing outputs (2 volt x 0.5 ms up to 10 vol x 1.5 ms). The final position for lead penetration was made by the operator blinded to the results of the IEST. Results IEST shortened the S-LVAT (δ-S-LVAT) up to 6.4±5 ms (range 0 to 18 ms), 8±8 ms (range 0 to 36 ms) and 5.5±5 ms (range 0 to 20 ms) respectively for high, mid, and low sites (Figure, panel A and B). There was not observed any paired correlation between the magnitude of the δ-S-LVAT at the three different positions (Pearson 0.36, 0.12 and 0.22; p= 0.1, 0.6 and 0.4 respectively), suggesting that the δ-S-LVAT is site specific. The final position for lead penetration was medium in 17 cases vs low in 6 cases. The low-output S-LVAT interval at the final position before lead penetration was positively correlated with the final S-LVAT achieved after lead penetration (Pearson 0.44; p=0.04), but the magnitude of the correlation increased with the high-output S-LVAT interval (Pearson 0.57; p=0.006) suggesting a better prediction performance (Figure, panel C). A complex relationship was observed where higher δ-S-LVAT values were associated with shorter S-LVAT after penetration and final position of the lead. In fact, for cases with low-output S-LVAT interval &amp;gt; 100 ms, the δ-S-LVAT significantly correlated with S-LVAT after penetration and final position of the lead (Pearson -0.61; p=0.026). Conclusions IEST lead to a site-specific shortening of the S-LVAT, pointing to optimized positions for LBB pacing. The technique provides with additional diagnostic criteria to determine the better site for lead penetration.

Management of impacted fetal head at cesarean birth: A systematic review and meta-analysis.

Despite increasing incidence of impacted fetal head at cesarean birth and associated injury, it is unclear which techniques are most effective for prevention and management. A high quality evidence review in accordance with international reporting standards is currently lacking. To address this gap, we aimed to identify, assess, and synthesize studies comparing techniques to prevent or manage impacted fetal head at cesarean birth prior to or at full cervical dilatation. We searched MEDLINE, Emcare, Embase and Cochrane databases up to 1 January 2023 (PROSPERO: CRD420212750016). Included were randomized controlled trials (any size) and non-randomized comparative studies (n ≥ 30 in each arm) comparing techniques or adjunctive measures to prevent or manage impacted fetal head at cesarean birth. Following screening and data extraction, we assessed risk of bias for individual studies using RoB2 and ROBINS-I, and certainty of evidence using GRADE. We synthesized data using meta-analysis where appropriate, including sensitivity analyses excluding data published in potential predatory journals or at risk of retraction. We identified 24 eligible studies (11 randomized and 13 non-randomized) including 3558 women, that compared vaginal disimpaction, reverse breech extraction, the Patwardhan method and/or the Fetal Pillow®. GRADE certainty of evidence was low or very low for all 96 outcomes across seven reported comparisons. Pooled analysis mostly showed no or equivocal differences in outcomes across comparisons of techniques. Although some maternal outcomes suggested differences between techniques (e.g., risk ratio of 3.41 [95% CI: 2.50-4.66] for uterine incision extension with vaginal disimpaction vs. reverse breech extraction), these were based on unreliable pooled estimates given very low GRADE certainty and, in some cases, additional risk of bias introduced by data published in potential predatory journals or at risk of retraction. The current weaknesses in the evidence base mean that no firm recommendations can be made about the superiority of any one impacted fetal head technique over another, indicating that high quality training is needed across the range of techniques. Future studies to improve the evidence base are urgently required, using a standard definition of impacted fetal head, agreed maternal and neonatal outcome sets for impacted fetal head, and internationally recommended reporting standards.

Improving HIV Pre-exposure Prophylaxis Uptake with Artificial Intelligence and Automation: A Systematic Review.

To identify studies promoting the use of artificial intelligence (AI) or automation with HIV pre-exposure prophylaxis (PrEP) care and explore ways for AI to be used in PrEP interventions. Systematic review. We searched in the US Centers for Disease Control and Prevention Research Synthesis database through November 2023 PROSPERO (CRD42023458870). We included studies published in English that reported using AI or automation in PrEP interventions. Two reviewers independently reviewed the full text and extracted data by using standard forms. Risk of bias was assessed using either the revised Cochrane risk-of-bias tool for randomized trials for randomized controlled trials or an adapted Newcastle-Ottawa Quality Assessment Scale for non-randomized studies. Our search identified 12 intervention studies (i.e., interventions that used AI/automation to improve PrEP care). Currently available intervention studies showed AI/automation interventions were acceptable and feasible in PrEP care while improving PrEP-related outcomes (i.e., knowledge, uptake, adherence, discussion with care providers). These interventions have used AI/automation to reduce workload (e.g., directly observed therapy) and helped non-HIV specialists prescribe PrEP with AI-generated clinical decision-support. Automated tools can also be developed with limited budget and staff experience. AI and automation have high potential to improve PrEP care. Despite limitations of included studies (e.g., the small sample sizes and lack of rigorous study design), our review suggests that by using aspects of AI and automation appropriately and wisely, these technologies may accelerate PrEP use and reduce HIV infection.

Aromatherapy for the prevention of postoperative nausea and vomiting: A systematic review and meta-analysis

ABSTRACT Objectives: Postoperative nausea and vomiting (PONV) are common complications following surgical procedures. While drug-based treatments are standard, there is increasing interest in nonpharmacological alternatives, such as aromatherapy, due to potential benefits and minimal side effects. This study aimed to assess the effectiveness of aromatherapy in preventing PONV. Materials and Methods: A comprehensive systematic review and meta-analysis were conducted using PubMed, Cochrane Library, EMBASE, and CINAHL databases for studies published up to May 2023. The included studies were randomized controlled trials (RCTs) and nonrandomized studies of interventions that examined the impact of aromatherapy on PONV. The risk of bias was assessed, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was employed to evaluate the certainty of the evidence. Results: Eleven studies were selected for review, with eight RCTs included in the meta-analysis. Aromatherapy effectively reduced postoperative nausea severity (standardized mean difference [SMD]: −0.93, 95% confidence interval [CI]: −1.64 to −0.22; P = 0.010), but the reduction in vomiting episodes was not statistically significant (SMD: −0.81, 95% CI: −1.98-0.37; P = 0.180). Subgroup analysis indicated that ginger essence, lavender, and peppermint oils were particularly effective in managing postoperative nausea. However, due to significant statistical heterogeneity and potential biases in the studies, the results should be interpreted with caution. The certainty of the evidence, as evaluated by the GRADE approach, was low. Conclusion: Preliminary evidence supports the potential benefit of aromatherapy in reducing the severity of postoperative nausea. However, given the low certainty of current evidence, more rigorous and standardized research is needed. The safety, affordability, and potential benefits to patient comfort make aromatherapy a promising area for further research in postoperative care.

Feasibility and outcomes of ultrasound-guided transcutaneous access to the axillary vein for implantation, revision, and upgrade of cardiac electronic devices

Abstract Background Implanting leads for cardiac implantable electronic devices (CIED) requires venous access. Venous access is commonly established through the cephalic and subclavian vein. For CIED upgrades or revisions, the preferred cephalic vein access is often not viable. Several reports suggest that fluoroscopy-guided axillary vein puncture may reduce thoracic complications. Purpose This study reports on procedural outcomes of ultrasound-guided axillary vein access for CIED implantation, revision, or upgrade in a large tertiary care centre. Outcomes were compared to the traditional subclavian vein approach. Methods This retrospective, single-center non-randomized study, conducted from January 2021 to August 2023, analyzed patients undergoing CIED implantation, revision, or upgrade. Axillary access, initially introduced by one operator, was increasingly adapted by additional operators. The axillary access was obtained by ultrasound-guided visualization of the axillary vein at the deltopectoral groove (Figure 1A and B). Subsequently, the wire(s) were transcutaneously inserted. An adjacent skin incision allowed for threading the wire(s) followed by standard lead implantation (Figure 1C). The study evaluated the acute success of each venous access method and the incidence of adverse events. Those were defined as pneumothorax, hemothorax, and pocket hematoma. An intention-to-treat analysis was performed. A p-value assessed the comparative outcomes between the axillary and subclavian access methods. Results In this study, 986 patients (mean age 74, IQR 64-82 years, 35% women) underwent CIED implantation, revision, or upgrade with 1636 lead implants. Axillary access was used in 578 patients with 532 (92%) successful implantations. Subclavian access yielded a higher success rate with 394/408 patients (97%) (p=0.003). For device upgrades or revisions specifically, axillary access was successful in 68/79 patients (86%), versus 44/47 patients (94%) with subclavian access (p=0.193). Acute complications were less frequent with axillary access (0.3%, 2/578 patients) and consisting of two cases of pneumothorax requiring intervention. In CIED implantations via subclavian access, complications occurred in 17/408 patients (4.2%) (p&amp;lt;0.001) including pneumothorax in 12 patients (2.9%, with 2% requiring intervention), hemothorax in three patients (0.7%), and pocket hematoma in two patients (0.5%). No additional complications were observed in the axillary group. Conclusion The implementation of transcutaneous, ultrasound-guided axillary access for CIED implantations, revisions and upgrades in a major CIED training centre is feasible. Complication rates were low compared to subclavian venous access.Figure 1

Transforming health care: Investigating Influenzer, a novel telemedicine-supported early discharge program for patients with lower respiratory tract infection: A non-randomized feasibility study.

The COVID-19 pandemic has posed unprecedented challenges to healthcare systems globally, necessitating innovative care models like hospital-at-home and virtual care programs. The Influenzer telemedicine program aims to deliver hospital-led monitoring and treatment to patients at home. Integrating telemedicine technology with domestic visits provides an alternative to traditional hospitalization, with the aim of easing the burden on healthcare facilities without compromising patient safety. To evaluate the effectiveness of the Influenzer program, a randomized controlled trial is proposed. This study aimed to assess the feasibility of the proposed clinical trial design. A non-randomized feasibility study was conducted at the Department of Pulmonary and Infectious Diseases at Nordsjaellands Hospital offering a telemedicine-supported early discharge program to patients with lower respiratory tract infections, including COVID-19. The feasibility of trial procedures, including recruitment, adherence, and retention, was analyzed. Also, participants' characteristics and trajectory during the intervention, including telemedicine and domestic services, were assessed. Nineteen patients were enrolled from June 2022 to April 2023 and treated at home. Forty patients were not enrolled as 15 (25%) were non-eligible according to study protocol, 15 (25%) refused to participate and 10 (17%) had not been approached. Subjects treated at home had comparable clinical outcomes to those treated in the acute hospital, no major safety incidences occurred and patients were highly satisfied. Participants demonstrated 99% adherence to planned daily monitoring activities. In total, 63% completed all survey assessments at least partially including baseline, at discharge, and 3 months post-discharge, while 89% participated in a follow-up interview. No participants withdrew their consent. The feasibility study documented that the Influenzer home-hospital program was feasible and well accepted in a Scandinavian setting in terms of no withdrawals and excellent participant adherence to the planned daily monitoring activities. Challenges in the organizational structures including patient recruitment and data collection required resolution prior to our randomized clinical trial. Insights from this feasibility study have led to the improved design of the final Influenzer program evaluation trial. ClinicalTrials.gov, NCT05087082. Registered on 18 August 2021.

Analysis of the occurrence of germline mutations BRCA1\2, PALB2, CHEK2, NBN in patients with pancreatic malignancies. Single-center cohort non-randomized retrospective study

Objective. To analyze the frequency of carriage of BRCA1\2, PALB2, CHEK2, NBN mutations in patients with malignant neoplasms of pancreas. Materials and methods. The single-center cohort non-randomized retrospective study is based on the data of 82 patients who were examined and treated in Russian Research Center of Radiology and Surgical Technologies named after academician A.M. Granov from 2020 to 2022. Patients with confirmed ductal adenocarcinoma of pancreas were included into the study group. Screening of mutations in exons 2,10, 18, 19 of BRCA1 gene and exon 11 of BRCA2 gene was performed in these patients. In addition, oncological family histories were studied. Results. Analysis of medical documentation data showed that 18 (22 %) patients with pancreatic cancer had a hereditary oncological history. In this cohort of patients, 5 (28 %) had relatives with pancreatic cancer, 9 (50 %) had a family history of ovarian cancer, 2 (11 %) female relatives of patients in the study group were diagnosed with breast cancer before the age of 50, also 2 (11 %) patients had a history of more than 2 relatives who suffered from breast cancer and / or prostate cancer. When evaluating the results of revealing the mutations in the entire study group (82 patients), BRCA1 (c.5266dupC) was revealed in 8 patients (9.7 %), PALB-2 (c.1592delT) – in 2 patients (2.4 %), mutations CHEK2, NBN and BRCA2 were not diagnosed in any patient. 5 (6 %) patients who were BRCA1 mutation carriers and one patient with an established PALB2 mutation, according to the analysis of case histories, had no oncological history. None of the patients in the study group was a carrier of the BRCA2, CHEK2 and NBN mutations. Conclusions. Some patients with pancreatic cancer are carriers of germline mutations. Considering our data on the trend of association between germline mutations and pancreatic cancer, we can make an assumption about the prospect of using this indicator as one of the markers for early detection of pancreatic cancer not only in patients with hereditary risk factors for neoplasia, but also in patients without cancer anamnesis. To obtain the results, further observation of patients in the study group and randomized multicenter studies are required.

The Effectiveness of Atezolizumab in Metastatic Large Cell Neuroendocrine Carcinoma of the Lungs: Insights from the LANCE Pilot Study

Background: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone. The primary outcomes measured were 12- and 24-month survival rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results: Of the 22 patients screened, 17 met the inclusion criteria and received either atezolizumab plus platinum-based chemotherapy (n = 10) or chemotherapy alone (n = 7). After a median follow-up of 23.3 months, the 12-month survival rate was 57.1% (95% CI: 32.6–100%) and 14.3% (95% CI: 2.33–87.7%) for the atezolizumab and the chemotherapy-only groups, respectively. The survival benefit for the atezolizumab group was sustained at 24 months (45.7% vs. 14.3%). Overall survival was significantly higher for the atezolizumab group, and PFS was non-significantly associated with the addition of atezolizumab (log-rank p = 0.04 and 0.05, respectively). Conclusions: This pilot study suggests that the addition of atezolizumab to standard platinum-based chemotherapy may provide a substantial survival benefit compared with chemotherapy alone in the first-line treatment of metastatic LCNEC.

#1519 Nutritional impact of ketoanalogue supplementation with protein-restricted diets in advanced chronic kidney disease

Abstract Background and Aims The benefits and risks of a protein-restricted diet supplemented with ketoanalogues (KA) in patients with chronic kidney disease (CKD) are still being explored. Combining KA supplementation with a protein-restricted diet may potentially preserve the glomerular filtration rate (GFR) in CKD patients. However, concerns about protein-energy wasting and the nutritional benefits of KA supplementation remain uncertain. Previous systematic reviews have often included crossover or non-randomized studies and combined data from CKD and dialysis patients, potentially introducing heterogeneity when assessing the effects of KA supplementation in CKD patients. We aim to provide an updated and comprehensive assessment of the impact of combining KA supplementation with a protein-restricted diet on the nutritional status of advanced CKD patients compared to the effects of a protein-restricted diet alone. Method We conducted systematic literature searches of PubMed, Embase, Scopus, and Cochrane Library up to September 2023. We selected parallel-design randomized controlled trials comparing KA supplementation to a low- or very low-protein diet (VLPD) versus a low-protein diet (LPD) alone in adults with stages 3-5 CKD. Outcomes included serum albumin, triceps skinfold (TSF), and mid-arm muscle circumference (MAMC). Pooled estimates of effect measures were calculated using the random-effects model and presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Given the variation in CKD stages among the included studies, subgroup analyses were conducted based on baseline renal function (GFR &amp;lt; 20 vs. ≥ 20 mL/min/1.73 m²). To assess the robustness of our meta-analyses, we conducted sensitivity analyses by excluding studies with an in-trial follow-up duration of less than one year. Results We identified 13 trials with 974 participants and a median follow-up of 12 months. KA supplementation combined with an LPD or a VLPD significantly increased TSF compared to an LPD alone (SMD, 0.25; 95% CI, 0.04, 0.45; P = 0.02; Fig. 1). No significant differences were observed in serum albumin (SMD, 0.28; 95% CI, -0.05, 0.61; P = 0.10; Fig.) and MAMC (SMD, 0.10; 95% CI, -0.12, 0.32; P = 0.37; Fig. 1). KA supplementation significantly increased serum albumin in patients with a baseline GFR ≥ 20 mL/min/1.73 m² (SMD 0.52; 95% CI, 0.20, 0.84; P = 0.001), but not in those with a baseline GFR &amp;lt; 20 mL/min/1.73 m² (SMD, -0.04; 95% CI, -0.41, 0.34; P = 0.85), and this difference between the subgroups was statistically significant (P = 0.03; Fig. 2). Sensitivity analysis that excluded studies with an in-trial follow-up duration of less than one year yielded results similar to the main analysis, except that the difference in TSF between the intervention and control arms became nonsignificant. Conclusion In patients with stages 3-5 CKD, KA supplementation with a protein-restricted diet did not adversely affect nutritional status. These findings remained consistent in sensitivity analyses of RCTs with a follow-up of more than one year and in subgroup analyses based on baseline GFR. The addition of KAs to protein-restricted diets improved serum albumin levels in patients with a baseline GFR of ≥ 20 mL/min/1.73 m². Our analyses confirmed the efficacy and safety of KA supplementation on nutritional status in advanced CKD patients over a one year follow-up period.

Robot-assisted versus traditional surgery in the treatment of intertrochanteric fractures: a meta-analysis

Intramedullary nail fixation of intertrochanteric fractures assisted by orthopedic surgical robot navigation is a new surgical method, but there are few studies comparing its efficacy with traditional intramedullary nail fixation. We aimed to assess whether robot-assisted internal fixation confers certain surgical advantages through a literature review. PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wan fang Data Knowledge service Platform were searched to collect randomized and non-randomized studies on patients with calcaneal fractures. Five studies were identified to compare the clinical indexes. For the clinical indexes, the technology of robot-assisted is generally feasible, in time to operation, intraoperative fluoroscopy times, blood loss, pine insertion, tip apex distance (TAD), and Harris score (P < 0.05). However, on the complication and excellent and good rate after operation did not show good efficacy compared with the traditional group (P > 0.05). Based on the current evidence, For the short-term clinical index, the advantages of robot-assisted are clear. The long-term clinical effects of the two methods are also good, but the robot-assisted shows better. However, the quality of some studies is low, and more high-quality randomized controlled trials (RCTs) are needed for further verification.

#3017 Renal-friendly lamivudine dosages are unlikely to contribute to HIV-1 shedding into PD effluents—an open label non-randomized pharmacokinetics study

Abstract Background and Aims Renally adjusted lamivudine dosages are effective. However, some of the kidney failure patients managed with lamivudine-containing regimens are failing to suppress HIV in peritoneal dialysis (CAPD) effluent. The steady-state lamivudine pharmacokinetics among these patients was evaluated. Method This overnight open-label pharmacokinetic study enrolled participants living with HIV and managed with CAPD. Lamivudine levels in blood serum and CAPD effluent samples were quantified using liquid chromatography coupled with a mass spectrometry. Pharmacokinetic measures were obtained through non-compartmental analysis. Results Twenty-eight participants were recruited with a median ARV duration of 8 (IQR, 4.5-10.5) years and a CAPD duration of 13.3 (IQR, 3.3-31.9) months. The majority, 78.6% (22/20) of participants received a 50 mg dose and 25% (1/4) had a detectable HIV viral load (HIV-VL) in CAPD, while 10.7% (3/28), and another 10.7% (3/28) received 75 mg and 300 mg dosages, respectively. Among those treated with 75 and 300 mg, 50% (2/4) and 25% (1/4) had detectable HIV-VL in CAPD, respectively. The peritoneal membrane characteristics and CAPD system strengths were variable across the entire study population. Lamivudine exposure was increased in blood serum (50 mg-AUC0-24 hours, 651.3 ng/mL; 75 mg-AUC0-24 hours, 677.84 ng/mL; 300 mg-AUC0-24 hours, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 hours, 384.91 ng/mL; 75 mg-AUC0-24 hours, 383.24 ng/mL; 300 mg-AUC0-24 hours, 2001.60 ng/mL) among the entire study population. The Cmax (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and Cmin (50 mg, 17.8 ng/mL; 75 mg, 16.4 ng/mL; 300 mg, 76.4 ng/mL) measured in serum were within the therapeutic levels. Conclusion Steady-state lamivudine pharmacokinetic measures were variable among the entire study population; however, the total lamivudine exposure was within the therapeutic levels.

Impact of metformin on melanoma: a meta-analysis and systematic review

BackgroundThere is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.MethodsSelection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using ‘Melanoma’ and ‘Metformin’ as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and I2 statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.ResultsA total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I2 = 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I2 = 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I2 = 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I2 = 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.DiscussionThe improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.

Efficacy of stem cell therapy in patients with chronic liver disease: an umbrella review of systematic reviews.

Stem cell therapy offers promising benefits like modulating immune responses, reducing inflammation, and aiding liver regeneration. This umbrella review seeks to compile evidence from systematic reviews to assess the efficacy of stem cell therapy for improving liver function and survival rates in chronic liver disease patients. We searched electronic databases up to February 15, 2024. The selection process focused on systematic reviews comparing stem cell therapy with standard care or a placebo. The primary outcomes evaluated were changes in liver enzymes, the MELD score, and survival rates. Nested Knowledge software was utilized for screening and data extraction. All statistical analyses were performed using R software, version 4.3. Our umbrella review included 28 systematic reviews. The meta-analysis showcased a notable improvement in survival rates with a pooled RR of 1.487 (95% CI: 1.281 to 1.727). In non-randomized studies, albumin levels exhibited an SMD of 0.786 (95% CI: 0.368 to 1.204), indicating positive therapeutic effects. For ALT, the meta-analysis revealed a decrease in levels with an SMD of -0.499 (95% CI: -0.834 to -0.164), and for AST, an overall SMD of -0.362 (95% CI: -0.659 to -0.066) was observed, suggesting hepatoprotective effects. No significant changes were observed in total bilirubin levels and MELD scores in RCTs. Stem cell therapy exhibits potential as a novel treatment for chronic liver diseases, as it has demonstrated improvements in survival rates and certain liver function markers. More high-quality RCTs are needed in the future to fully ascertain the efficacy of stem cell therapy in this patient population.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review (protocol)

Objective To determine the efficacy and safety of CAR-T therapy in the treatment of patients with hematologic malignancies, in comparison with other current therapies. Design A living systematic review Methods We will include randomized trials evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, best supportive care or any other intervention in patients with hematologic malignancies. Non-randomized primary studies will be searched in case we found no direct evidence from randomized controlled trials. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. Efficacy measures will include overall survival rate, overall response rate, complete response/remission (CR) rate, partial response/remission (PR) rate, relapse from CR, progression-free survival, and time from CAR-T infusion to transplantation. Safety measures will include serious adverse events, the incidence of cytokine release syndrome, graft-versus-host disease, neurotoxicity, and total adverse events. Quality of life will also be assessed. Meta-analyses will be carried out to summarize the results. We will apply the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available until there is solid evidence to respond to the review objective. We will resubmit it for publication every time the conclusions change or whenever there are substantial updates.

The criteria for chronic rhinosinusitis in children with cystic fibrosis are rarely fulfilled after initiation of CFTR modulator treatment.

The vast majority of people with cystic fibrosis (pwCF) have untreated secondary chronic rhinosinusitis (CRS). Whereas the introduction of the cystic fibrosis transmembrane conductance regulator modulator (CFTRm) treatment regime has improved the lung function of pwCF, few studies have been published examining the effect on sinonasal symptoms in children. Our aim was to explore the effect of double CFTRm treatment on CRS and olfaction in children with CF. pwCF were included in this non-randomized cross-sectional study, where an otolaryngologist performed a complete ENT examination before initiating treatment with elaxacaftor/tezacaftor/ivacaftor (ETI). Twenty-three pwCF aged 6-12 years were included. Eighteen of 23 patients were on a double CFTRm treatment, and 5 patients were CFTRm naive, respectively. Altogether, 19 had normal olfaction, 20 had none or mild CRS symptoms according to SNOT-22, and 14 had a normal endoscopy. None of the patients had symptoms of chronic rhinosinusitis lasting for more than 12 weeks, thus none of the patients fulfilled the criteria for CRS. Children with CF treated with double CFTRm have few to no symptoms of CRS and normal olfaction, which is an improvement compared with children following treatment modalities prior to CFTRm.

Efficacy of laser hair removal in hidradenitis suppurativa: A systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory condition characterized by painful nodules, draining tunnels, and fibrotic scarring in intertriginous, hair-bearing areas. The pathogenesis involves follicular occlusion and subsequent rupture, leading to uncontrolled inflammation. Treatment options for HS are limited and lack universal effectiveness. Laser hair removal (LHR) has been explored as a potential treatment; however, the efficacy and appropriate laser modalities remain unclear. This systematic review examined the efficacy and adverse effects of LHR in HS. A comprehensive literature search was conducted from inception to September 2023 in Ovid MEDLINE, Ovid Embase, and The Cochrane Library (Wiley) with predefined inclusion and exclusion criteria, and a meta-analysis was conducted. Ten studies were selected (n = 227 total patients) and included six randomized controlled trials, two nonrandomized experimental studies, and two case series. Various laser modalities, including long-pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) (n = 115), intense pulsed light (n = 18), Alexandrite (n = 54), intralesional 1064 nm diode (n = 20), and combined fractional CO2 and long-pulsed Nd:YAG laser (n = 20), consistently demonstrated significant improvement in HS disease severity, irrespective of the disease scoring method used. Minimal adverse effects (primarily mild pain and erythema) were reported. A meta-analysis of three studies utilizing long-pulsed Nd:YAG laser demonstrated a standardized mean difference in disease severity of -1.68 (95% confidence interval: -2.99; -0.37), favoring treatment with LHR for HS. Hair follicles are key in HS pathogenesis and all included studies showed a significant improvement in HS disease severity after LHR regardless of the laser device used, likely related to hair follicle unit destruction. HS is a complex and heterogenous condition, and multiple disease scoring methods complicate outcome comparisons across studies. However, LHR, utilizing various techniques, is an effective treatment option for HS with minimal adverse effects.

The Patient Activation Measure-13 (PAM-13) in an oncology patient population: psychometric properties and dimensionality evaluation

BackgroundAccurate assessment and enhancement of health-related skills among oncology patients are pivotal for optimizing cancer care. The Patient Activation Measure (PAM-13), a questionnaire designed to reflect an individual’s knowledge, skills, and confidence in self-healthcare management, has been validated across diverse countries and settings. Concerns have been raised regarding the cross-situational applicability, as patients with specific diseases and cultural backgrounds interpret questionnaire items differently. This study aimed to examine the structural validity and psychometric properties of the PAM-13 in an oncological patient cohort.MethodsBaseline data from a longitudinal non-randomized controlled study involving cancer out-patients (n = 1,125) from Comprehensive Cancer Centres in Southern Germany were analysed. The German version of the PAM-13 was employed. With classical test and item response theory methods data quality, reliability, convergent and structural validity, as well as psychometric properties were assessed. Exploratory (EFA) and confirmatory factor analyses (CFA) were employed to investigate the postulated unidimensionality of the underlying construct. With a partial credit model (PCM) we examined item fit, targeting, local independence and differential item functioning.ResultsParticipants were predominantly female (73.0%) with a breast cancer diagnosis (41.3%). While items were generally well-accepted, ceiling effects were observed and a high mean PAM-13 score (69.7, SD = 14.2) was noted, potentially compromising responsiveness to interventions. Reliability was adequate (Cronbach’s α = 0.81), person and item separation reliability were good to excellent (0.81 and 0.99, respectively). Explorations of the unidimensionality of the construct (EFA, CFA, PCM) yielded inconclusive results, hinting towards a two-factor solution. Item difficulty rankings deviated from the original. No differential item functioning was identified, and local independence was confirmed.ConclusionsWhile the PAM-13 serves as a valuable instrument for comprehending and promoting health-related skills in cancer patients, the identification of ceiling effects, disordered item-difficulty rankings, and inconclusive findings regarding unidimensionality contribute to the expanding body of evidence, emphasizing the dependency of PAM-13’s validity and reliability on distinctive characteristics within the population under investigation. Future research should prioritize refining or adding PAM-13 items to better capture the specific health-related challenges within diverse populations, paving the way for more effective patient engagement strategies in oncology.Trial registration numberDRKS00021779