Clinical Effects Research Articles

Эффективность использования новой роботической системы Versius для выполнения операций у детей: результаты клинических испытаний

Authors represent the Russia’s first research demonstrating the results of the use of the Versius modular & portable surgical robot by “CMR Surgical,” Ltd. (Cambridge, Cambridgeshire, United Kingdom) in surgical interventions on pediatric patients that they’ve obtained as part of the clinical trials complex approved by the Federal Service for Surveillance in Healthcare of Russia (“Roszdravnadzor”). The purpose of this research was to obtain practical evidence of the clinical safety and effectiveness of the use of the new Versius® Surgical Robotic System in minimally invasive surgical interventions on children. The criteria for the safety and effectiveness of the method were the absence of complications caused by the Surgical Robotic System (SRS) operation or the surgical technique as well as the absence of dropping into either laparoscopy or open surgery technique. Material and methods used: non-randomized single-center controlled trial had been carried out in children aged 1 to 18 y/o. Areas of application for surgical procedures included urology, abdominal and thoracic surgeries. Results: the number of patients who had undergone the robot-assisted surgeries had totaled 55 (27 (49%) m/28 (51%) f). The patient’s median age of the surgical intervention was 11.5 [7.0; 15.0] y/o; the median weight was 45.5 [27.0; 59.0] kilograms; the median surgical intervention duration was 140.0 [85.0; 175.0] minutes; patients’ stay in the intensive care unit had averaged for 23.0 [19.0; 24.0] hours; the average hospitalization duration was 8.0 [4.0; 14.0] days. Surgical interventions weren’t accompanied by any of the intraoperative complications such as bleeding, organ perforation and/or injury to adjacent anatomical structures. Conversions to either laparoscopic or open surgery technique also weren’t recorded. The equipment technical problems with SRS such as sudden system power-off, synchronous interaction of joysticks/manipulators interruption, robotic arms blocking, manipulators’ uncontrolled movement and/or traumatic effects on the tissues of the abdominal wall/chest weren’t recorded as well. Conclusion: the preliminary results obtained from the clinical trials complex affirm the potential ability of the Versius® Surgical Robotic System to performing robotic surgical interventions on pediatric patients aged 1 to 18 years old.

Matched Comparison Examining the Effect of Obesity on Clinical, Economic, and Humanistic Outcomes in Patients with BipolarI Disorder.

BipolarI disorder (BD-I) is associated with an increased risk of obesity, but few studies have evaluated the real-world clinical, humanistic, and economic effects associated with obesity in people with BD-I. This was a retrospective, cross-sectional analysis of responses to the 2016 and 2020 National Health and Wellness surveys. Respondents (18-64years) with a self-reported physician diagnosis of BD-I were matched to controls without BD-I based on demographic and health characteristics. Respondents were categorized by body mass index as underweight/normal weight (< 25kg/m2), overweight (25 to < 30kg/m2), or obese (≥ 30kg/m2). Multivariable regression models were used to compare obesity-related comorbidities, healthcare resource utilization (HCRU), health-related quality of life (HRQoL), work productivity, and indirect and direct costs. Before matching, the BD-I cohort was younger than the non-BD-I cohort and included more female and white respondents and a greater proportion covered by Medicaid or Medicare. After matching, the BD-I and non-BD-I cohorts had similar characteristics. A total of 5418 respondents (BD-I, n = 1806; matched controls, n = 3612) were analyzed. Obese respondents with BD-I reported the highest adjusted prevalences of high blood pressure (50%), high cholesterol (35%), sleep apnea (27%), osteoarthritis (17%), type2 diabetes (12%), and liver disease (4%). Obesity in respondents with BD-I was associated with the lowest HRQoL scores. Measures of work impairment were highest in respondents with BD-I and obesity, as was HCRU. Respondents with BD-I and obesity had the highest associated total indirect and direct medical costs ($25,849 and $44,482, respectively). Obese respondents with BD-I had greater frequencies of obesity-related comorbidities, higher HCRU, lower HRQoL, greater work impairments, and higher indirect and direct medical costs. These findings highlight the real-world burden of obesity in people with BD-I and the importance of considering treatments that may reduce this burden.

Local application of 0.8% hyaluronic acid gel as an adjunct to minimally invasive nonsurgical treatment of periodontal intrabony defects-A randomized clinical trial.

The aim of this study was to evaluate the clinical and radiographic effects of hyaluronic acid (HA) gel application as an adjunct to minimally invasive nonsurgical treatment (MINST) in intrabony defects ≥3 mm. A total of 36 patients were included and randomly assigned to two groups: (a) MINST + HA (test; n = 17) and (b) MINST (control, n = 19). Subgingival 0.8% HA gel was applied in intrabony defects of test group and repeated 4 weeks following MINST protocol. Clinical measurements including probing depth (PD), clinical attachment level (CAL), and gingival recession (GR) were recorded at baseline and repeated at 3 and 6 months. Radiographic evaluation was performed at baseline and 6 months. Test group showed significantly greater reduction in PD and gain in CAL at 3 months compared to baseline than that of controls (p < .05), but the changes (Δ) at 6 months compared to baseline did not differ between the groups (p > .05). Although, both groups showed statistically significant GR in all evaluated time periods (p < .05), control group showed higher ΔGR than that of test group (p < .05). There was no significant difference between the groups in terms of radiographic defect fill/bone gain (p > .05). The additional use of 0.8% HA gel in the treatment of periodontal intrabony defects did not provide additional benefits in clinical and radiographic parameters. On the other hand, GR measurements showed favorable results in the test group.

Patient-reported preferences for subcutaneous or intravenous administration of parenteral drug treatments in adults with immune disorders: a systematic review and meta-analysis.

Aim: Several studies have found subcutaneous (SC) and intravenous (IV) administration of similar drugs for long-lasting immunological and autoimmune diseases to have similar clinical effectiveness, meaning that what patients report they prefer is, or should be, a major factor in treatment choices. Therefore, it is important to systematically compile evidence regarding patient preferences, treatment satisfaction and health-related quality of life (HRQL) using SC or IV administration of the same drug. Materials & methods: PubMed database searches were run on 15 October 2021. Studies involving patients with experience of both home-based SC and hospital-based IV administration of immunoglobulins or biological therapies for the treatment of any autoimmune disease or primary immunodeficiencies (PIDs) were included. The outcomes assessed were patient preferences, treatment satisfaction and HRQL. Preference data were meta-analyzed using a random-effects model. Results: In total, 3504 citations were screened, and 46 publications describing 37 studies were included in the review. There was a strong overall preference for SC over IV administration, with similar results seen for PIDs and autoimmune diseases: PID, 80% (95% confidence interval [CI], 64-94%) preferred SC; autoimmune diseases, 83% (95% CI: 73-92%); overall, 82% (95% CI: 75-89%). The meta-analysis also found that 84% (95% CI: 75-92%) of patients preferred administration at home to treatment in hospital. Analysis of treatment satisfaction using the life quality index found consistently better treatment interference and treatment setting scores with SC administration than with IV administration. Conclusion: Compared with IV infusions in hospital, patients tend to prefer, to be more satisfied with and to report better HRQL with SC administration of the same drug at home, primarily due to the greater convenience. This study contributes to evidence-based care of patients with autoimmune diseases or PIDs.

Long-Term Effectiveness and Reasons for Discontinuation of Dupilumab in Patients With Atopic Dermatitis.

Limited data are available on the long-term effectiveness and safety of dupilumab for atopic dermatitis (AD) in daily practice. To evaluate clinical effectiveness and reasons for discontinuation of dupilumab treatment in children, adults, and older adults with AD with up to 5 years of treatment in daily practice. This prospective multicenter cohort study was conducted using the BioDay registry (4 academic and 10 nonacademic hospitals in the Netherlands) to identify patients with AD of all ages who were treated with dupilumab between October 2017 and December 2022. Clinical effectiveness was evaluated by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), and numeric rating scale (NRS) for pruritus, stratified by children (<18 years), adults (18-64 years), and older adults (≥65 years). In addition, time to response, treatment responders, EASI subscores, second treatment episodes, and thymus- and activation-related chemokine and eosinophil levels were assessed. For patients who discontinued dupilumab, the reason for discontinuation was evaluated. In total, 1286 patients with AD (median [IQR] age, 38 [26-54] years; 726 [56.6%] male) were treated with dupilumab, including 130 children, 1025 adults, and 131 older adults. The median (IQR) follow-up time was 87.5 (32.0-157.0) weeks. Most patients maintained controlled AD, with EASI of 7 or lower and NRS for pruritus of 4 or lower varying between 78.6% and 92.3% and 72.2% and 88.2% for up to 5 years of treatment, respectively, while up to 70.5% of all patients prolonged the dosing interval to mostly 300 mg every 3 or 4 weeks. Mean EASI and NRS for pruritus were 2.7 (95% CI, 1.2-4.2) and 3.5 (95% CI, 2.7-4.3), respectively, after 5 years of treatment. Statistically significant differences between age groups were found over time for EASI and IGA; however, differences were rather small (week 52: EASI, 0.3-1.6; IGA, 0.12-0.26). No statistically significant differences between age groups were found for NRS for pruritus. Median thymus- and activation-related chemokine levels considerably decreased from 1751 pg/mL (95% CI, 1614-1900 pg/mL) to 390 pg/mL (95% CI, 368-413 pg/mL) after 6 months of treatment and remained low. Median eosinophil levels temporarily increased up to week 16, with a subsequently statistically significant decrease over time. In total, 306 patients (23.8%) discontinued dupilumab after a median (IQR) of 54.0 (29.0-110.00) weeks, with adverse events among 98 patients (7.6%) and ineffectiveness among 85 patients (6.6%) as the most frequently reported reasons. Forty-one patients (3.2%) restarted dupilumab, and most of these patients recaptured response. In this cohort study with up to 5 years of follow-up, dupilumab maintained its clinical effectiveness, while two-thirds of patients tapered to a dosing interval of every 3 or 4 weeks. Treatment was discontinued in 23.8% of patients mainly due to adverse events and/or ineffectiveness.

A Real-World Comparison of Clinical Effectiveness in Patients with Rheumatoid Arthritis Treated with Upadacitinib, Tumor Necrosis Factor Inhibitors, and Other Advanced Therapies After Switching from an Initial Tumor Necrosis Factor Inhibitor.

This study compared the clinical effectiveness of switching from tumor necrosis factor inhibitor (TNFi) to upadacitinib (TNFi-UPA), another TNFi (TNFi-TNFi), or an advanced therapy with another mechanism of action (TNFi-other MOA) in patients with rheumatoid arthritis (RA). Data were drawn from the Adelphi RA Disease Specific Programme™, a cross-sectional survey administered to rheumatologists and their consulting patients in Germany, France, Italy, Spain, the UK, Japan, Canada, and the USA from May2021 to January 2022. Patients who switched treatment from an initial TNFi were stratified by subsequent therapy of interest: TNFi-UPA, TNFi-TNFi, or TNFi-other MOA. Physician-reported clinical outcomes including disease activity (with formal DAS28 scoring available for 29% of patients) categorized as remission, low/moderate/high disease activity, as well as pain were recorded at initiation of current treatment and ≥ 6months from treatment switch. Fatigue and treatment adherence were measured ≥ 6months from treatment switch. Inverse-probability-weighted regression adjustment compared outcomes by subsequent class of therapy: TNFi-UPA versus TNFi-TNFi, or TNFi-UPA versus TNFi-other MOA. Of 503 patients who switched from their first TNFi, 261 were in TNFi-UPA, 128 in TNFi-TNFi, and 114 in TNFi-other MOA groups. At the time of switch, most patients had moderate/high disease activity (TNFi-UPA: 73%; TNFi-TNFi: 52%; TNFi-other MOA: 60%). After adjustment for differences in characteristics at point of switch, patients in TNFi-UPA group (n = 261) were significantly more likely to achieve physician-reported remission (67.7% vs. 40.3%; p = 0.0015), no pain (55.7% vs. 25.4%; p = 0.0007), and complete adherence (60.0% vs. 34.2%; p = 0.0049) compared with patients in TNFi-TNFi group (n = 121). Similar findings were observed for TNFi-UPA versus TNFi-other MOA groups (n = 111). Patients who switched from TNFi to UPA had significantly better clinical outcomes of remission, no pain, and complete adherence than those who cycled TNFi or switched to another MOA.

Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial.

The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established. To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system. Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders. Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses. These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

Clinical effects of a home care program for patients with peritoneal dialysis in a tertiary care hospital.

Digital health technologies have been rapidly adopted during the coronavirus disease 2019 pandemic. In Korea, a home care program, including face-to-face educational consultation and remote patient monitoring, was initiated to improve patients' quality of life. This study focused on patients with end-stage renal disease undergoing peritoneal dialysis to verify the long-term clinical effectiveness of this home care program. This retrospective cohort study was designed as a pre-post study to analyze the clinical impact of a home care program for patients undergoing peritoneal dialysis in a single tertiary care hospital. A total of 186 patients were selected from June 2017 to May 2022 to identify clinical changes after program implementation by analyzing changes in peritonitis incidence and laboratory test results. Interrupted time series analyses with ordinary least squares linear regression and chi-square tests were used. At baseline, the incidence of peritonitis continuously increased by 0.480 cases per 1,000 patient-months (p = 0.02). After program initiation, the trend significantly decreased by 0.886 cases per 1,000 patient-months (p = 0.02). In addition, the proportion of individuals reaching the clinical target range had increased calcium levels (4.9%p, p = 0.003), stable hemoglobin (1.2%p, p = 0.477), phosphorus (2.8%p, p = 0.09), potassium (-1.6%p, p = 0.22), while parathyroid hormone levels decreased (-6.6%p, p = 0.005). With a reduction in peritonitis incidence and overall improvement in laboratory test results, our study suggests that conducting a home care program for patients undergoing peritoneal dialysis is clinically effective.

The impact of targeted local outreach clinics to improve COVID-19 vaccine uptake: controlled interrupted time series in South West England

BackgroundOutreach clinics were part of efforts to maximise uptake in COVID-19 vaccination.MethodsWe used controlled interrupted time series, matching on age, sex, deprivation and vaccination eligibility date, to determine the effect of outreach clinics on time to first COVID-19 vaccine, using a population-based electronic health record database of 914,478 people, from December 2020 to December 2021; people living within 1 mile of each outreach clinics were exposed.Results50% of 288,473 exposed citizens were white British, and 71% were aged 0–49 years. There was no evidence for an overall statistically significant increase in cumulative percentage vaccinated due to the outreach clinic at 6 weeks, with an overall pooled effect estimate of -0.07% (95% CI: -1.15%, 1.02%). The pooled estimate for increased cumulative vaccine uptake varied slightly depending on how the analysis was stratified; by ethnic group it was − 0.12% (95% CI: -0.90%, 0.66%); by age group it was − 0.06% (95% CI: -0.41%, 0.28%); and by deprivation it was 0.03% (95% CI: -0.74%, 0.79%).ConclusionsLiving within a mile of an outreach clinic was not associated with higher vaccine uptake. Evaluation of future outreach clinics should consider the relative importance of travel amongst other barriers to accessing vaccines.

Nutritional Interventions in Adult Patients With Irritable Bowel Syndrome: An Umbrella Review of Systematic Reviews and Meta-analyses of Randomized Clinical Trials.

There is still debate regarding the effect of nutritional interventions in improving irritable bowel syndrome (IBS) symptoms. The aim was to examine the evidence certainty and validity of all existing meta-analyses of intervention trials on nutritional interventions in patients with IBS. Scopus, PubMed, and Web of Science were reviewed until June 2023. Meta-analyses assessing the impacts of nutritional interventions in adults with IBS were entered. Effect sizes of nutritional interventions were recalculated by applying a random-effects model. GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) was implemented to determine evidence certainty. A total of 175 trials in 58 meta-analyses were entered describing the effects of 11 nutritional interventions on IBS-related outcomes. Nutritional interventions had beneficial effects on some IBS-related outcomes. For instance, soluble fiber, peppermint oil, and aloe vera improved IBS symptoms, and vitamin D3 and curcumin improved IBS symptom severity. Tongxieyaofang improved abdominal pain severity and stool frequency. Nevertheless, these outcomes have mainly shown small effects and low to very low evidence certainty. With regard to abdominal pain after probiotic supplementation (relative risk [RR]: 4.04; 95% confidence interval [CI]: 2.36, 6.92; GRADE = moderate) and IBS symptoms after a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (RR: 1.48; 95% CI: 1.14, 1.93; GRADE = moderate), there was evidence that probiotics and a low-FODMAP diet can confer clinical and favorable effects. The current review does not support nutritional interventions for improving IBS symptoms. With regard to probiotics and a low-FODMAP diet, considering limitations like short-term study duration, there was an influential clinical impact. PROSPERO registration no. CRD42023429991.

Medical perspectives on Israeli children after their release from captivity - A retrospective study.

Following the Hamas terror attack on Israeli towns on October 2023, 250 individuals were taken into captivity. On November-December 2023, during the cease-fire deal, 26 women and children were released. This study is the first to describe the physical and behavioural findings in children and their mothers in the immediate phase of returning home from captivity. This is a retrospective study describing the clinical characteristics of the returnees after 49-53 days in captivity. Patients were admitted to a designated unit in the Schnieder Children's Medical Center of Israel on November-December 2023. The hospitalisation duration was 1-9 days. All patients were evaluated according to a detailed protocol and were treated respectively. Patient population included 19 children (ranged 2-18 years old) and 7 women (ranged 34-78 years old). The most common clinical findings upon return included significant weight loss, psychological trauma, complications of poor hygiene and complications of recent shrapnel injuries. Microbiology tests were positive for multiple gastrointestinal pathogens. Serologic screening tests were positive for various infectious diseases. Clinical findings in this time period were diverse and required the attention of a multidisciplinary team. Long term clinical and psychological effects are yet to be known.

Venomous Aquarium Fish Stings

Despite the rarity of venomous aquarium fish stings, physicians sometimes encounter them. Therefore, it is essential to be familiar with these stings’ clinical effects and know how to approach and treat them. I searched through PubMed, PubMed Central, Scopus, and Google Scholar and found only a few case reports on this subject. To the best of my knowledge, no published articles review or present case series about all venomous aquarium fish, explaining their stings’ clinical manifestations and management. As you know, some aquarium fish, such as piranhas and snakeheads, are not venomous, but they may bite the finger or hand

Clinical efficacy of gamma-oryzanol combined with Femoston for perimenopausal syndrome.

Perimenopausal syndrome (PMS) is a chronic disease associated with estrogen deficiency. Because of the unsatisfactory outcomes of current conventional treatments for this condition, its treatment must be continuously explored and optimized. To assess the clinical effectiveness of γ-oryzanol in combination with Femoston for PMS. A total of 119 patients with PMS were selected from June 2023 to December 2023, which included 59 and 60 patients in the control and observation group, respectively. The control and observation groups were treated with Femoston and γ-oryzanol + Femoston, respectively. Comparative analyses were performed in terms of clinical effectiveness, safety (dizziness and headache, nausea and vomiting, and breast tenderness), sex hormones [estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)], lumbar spine (L1-4) and bilateral femoral bone mineral density (BMD), and sleep quality (sleeping time and frequency of awakenings from sleep). Compared with the control group, the observation group had statistically higher total effective rates of treatment; lower overall incidence of adverse events; higher post-treatment E2 levels and L1-4 and bilateral femoral BMD; and lower LH and FSH levels, sleeping time, and frequency of awakenings from sleep after treatment. Therefore, for the treatment of PMS, γ-oryzanol combined with Femoston is significantly better than Femoston alone in terms of clinical effectiveness, exhibiting more pronounced clinical advantages in improving safety, sex hormone levels, BMD, and sleep quality.

An Update on Colistin in Clinical Healthcare Unit in the Kingdom of Saudi Arabia: A Narrative Review.

Globally, gram-negative bacteria are a significant cause of morbidity. Multi-drug resistance bacteria are responsible for an increasing surge in infections that place a high cost on healthcare systems around the world. Recently, colistin, an antibiotic belonging to the polymyxin family, was reintroduced to combat multidrug- resistant gram-negative bacteria. Excessive and persistent use of colistin has led to the development and spread of colistin-resistant gram-negative bacteria throughout the globe. Healthcare units in various countries, including Saudi Arabia, are currently battling colistin-resistant gram-negative bacteria. Recently, colistin-resistant gram-negative bacteria have become a major health concern in Saudi Arabia. Hence, extensive epidemiological surveys and studies are required to understand the current status of the colistin antibiotic. Examining the knowledge currently available to the medical community on the molecular mechanism, clinical effectiveness, molecular epidemiology, and bacterial resistance to colistin in Saudi Arabia is the aim of this review.

Comparison of clinical and radiographic outcomes of bilateral versus unilateral ramus fixation in straddle fractures with posterior pelvic ring injury.

Superior and inferior ramus fractures, termed straddle fractures, are high-energy fractures often accompanied by unstable pelvic ring injuries. However, consensus is lacking regarding indications for surgical treatment or fixation methods. We aimed to compare clinical and radiological outcomes of unilateral ramus fixation (URF) and bilateral ramus fixation (BRF) for straddle fractures with unilateral posterior pelvic ring injuries. We enrolled 118 patients (73 males, 45 females; mean age, 47 years) diagnosed with straddle fractures between March 2015 and December 2021 with > 1 year of follow-up. Patients were divided into URF (n = 60) and BRF (n = 58) groups based on the anterior pelvic ring fixation method. Preoperative factors including body mass index, diabetes, smoking, injury mechanism, injury severity score, American Society of Anesthesiologists classification system, Tile classification, and Young and Burgess classification were compared. Intraoperative blood loss, operation time, postoperative bone union rate, complications, and the need for additional surgeries were analyzed. There were no statistically significant preoperative differences between the two groups. However, the URF group showed a significantly lower mean operative time and blood transfusion requirement (63min and 2 units, respectively) than the BRF group (104min and 3 units, respectively) (both p < 0.001). Postoperatively, bone union was achieved in 57 (95.0%) and 56 (96.6%) patients in the URF and BRF groups, respectively. Complications occurred in 17 (28.3%) and 14 (24.1%) patients in the URF and BRF groups, respectively, with additional surgeries needed in 3 (5.0%) patients in the URF group and 2 (3.4%) patients in the BRF group. Unilateral anterior fixation can provide sufficient stability and clinical effectiveness in the surgical treatment of straddle fractures in areas with posterior pelvic ring injuries. Compared with bilateral anterior fixation, unilateral fixation significantly reduces operation time and blood loss, making it a viable fixation method for straddle fractures.

A Comprehensive ddPCR Strategy for Sensitive and Reliable Monitoring of CAR-T Cell Kinetics in Clinical Applications

In this study, we present the design, implementation, and successful use of digital droplet PCR (ddPCR) for the monitoring of chimeric antigen receptor T-cell (CAR-T) expansion in patients with B-cell malignancies treated with different CAR-T products at our clinical center. Initially, we designed a specific and highly sensitive ddPCR assay targeting the junction between the 4-1BB and CD3ζ domains of tisa-cel, normalized with RPP30, and validated it using blood samples from the first tisa-cel-treated patient in Switzerland. We further compared this assay with a published qPCR (quantitative real-time PCR) design. Both assays showed reliable quantification of CAR-T copies down to 20 copies/µg DNA. The reproducibility and precision were confirmed through extensive testing and inter-laboratory comparisons. With the introduction of other CAR-T products, we also developed a corresponding ddPCR assay targeting axi-cel and brexu-cel, demonstrating high specificity and sensitivity with a limit of detection of 20 copies/µg DNA. These assays are suitable for CAR-T copy number quantification across multiple sample types, including peripheral blood, bone marrow, and lymph node biopsy material, showing robust performance and indicating the presence of CAR-T cells not only in the blood but also in target tissues. Longitudinal monitoring of CAR-T cell kinetics in 141 patients treated with tisa-cel, axi-cel, or brexu-cel revealed significant expansion and long-term persistence. Peak expansion correlated with clinical outcomes and adverse effects, as is now well known. Additionally, we quantified the CAR-T mRNA expression, showing a high correlation with DNA copy numbers and confirming active transgene expression. Our results highlight the quality of ddPCR for CAR-T monitoring, providing a sensitive, precise, and reproducible method suitable for clinical applications. This approach can be adapted for future CAR-T products and will support the monitoring and the management of CAR-T cell therapies.

Clinical effect of botulinum toxin type A combined with autologous fat grafting in patients with nasolabial fold depression.

Nasolabial fold (NLF) depression can affect the facial appearance of patients to some extent and increase their psychological burdens. In recent years, autologous fat grafting (AFG) combined with botulinum toxin A (BTX-A) injection (AFG + BTX-A injection) has been gradually applied in the treatment of patients with NLF depression. Although studies have been conducted on the efficacy and safety of AFG + BTX-A injection in treating NLF depression, the experimental design, observational indicators, and sample enrollment criteria vary remarkably, making it difficult to draw convincing and consistent conclusions. Thus, further relevant research is warranted. To assess the esthetic improvement, efficacy, and safety of AFG + BTX-A injections in patients with NLF depression. This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021. These patients were categorized into control (n = 30) and observation (n = 30) groups. The observation group received AFG + BTX-A injection, whereas the control group underwent AFG only. All patients were evaluated using the wrinkle severity rating scale (WSRS) and global aesthetic improvement scale. The compactness of facial contours, skin evaluation indexes, adverse reactions, and satisfaction of the two groups were evaluated 3 months postoperatively. The WSRS scores of the observation group at 1, 3, and 6 months postoperatively were lower than those of the control group (P < 0.05). Three months postoperatively, facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group (P < 0.05). The compactness of facial contours was better in the observation group than in the control group (P < 0.05). In addition, no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness, facial asymmetry, facial bruising, and facial concavity inequality (P > 0.05). AFG + BTX-A injection is a highly safe, cost-effective, effective, and long-lasting treatment for NLF depression with high esthetic value, which should be promoted in the future.

The effectiveness of neck stretching exercises in alleviating neck pain and self-reported disability after thyroidectomy: A systematic review and meta-analysis of clinical trials.

Thyroidectomy can lead to significant challenges such as neck pain, disability, and limited range of motion. Therefore, our objective is to conduct a systematic review and meta-analysis of clinical trials to investigate the clinical effectiveness of neck stretching exercises in alleviating neck pain and self-reported disability immediately after thyroidectomy. We systematically searched PubMed, CENTRAL, Scopus, and Web of Science from inception until July 28th, 2023. We assessed the selected trials for the risk of bias using both the RoB-2 and ROBINS-I tools. Our specific outcomes were the severity of neck pain and self-reported disability after thyroidectomy. The results were synthesized using risk ratio (RR) and standardized mean differences (SMD) with 95% confidence intervals (CI) in a random-effects model using Stata software. Nine clinical trials, comprising five randomized and four non-randomized trials, were included, with a total of 1026 patients. Neck stretching exercises were significantly associated with improved mean pain scores both after 1 week (n = 625 patients, SMD = -2.43, 95% CI [-4.65, -0.22], p = 0.03, I2 = 98%) and 1 month (n = 545 patients, SMD = -4.11, 95% CI [-8.12, -0.11], p = 0.04, I2 = 99%). Similarly, neck stretching exercises were significantly associated with improved mean self-reported disability scores both after 1 week (n = 298 patients, SMD = -0.70, 95% CI [-1.36, -0.04], p = 0.04, I2 = 87%) and 1 month (n = 298 patients, SMD = -0.42, 95% CI [-0.65, -0.19], p = 0.0004, I2 = 0%). The pooled analysis showed heterogeneity (chi-square p < 0.01, I2 > 80%), except for the mean self-reported neck disability score after 1 month, which showed homogeneity (chi-square p > 0.01, I2 = 0%). This systematic review and meta-analysis, involving 1026 patients, revealed the potential benefits of neck stretching exercises in alleviating neck pain and self-reported disability after thyroidectomy. However, further research is required to address methodological limitations, evaluate long-term outcomes, investigate potential moderators (i.e., the duration or intensity of the exercise program), and explore patients' analgesic consumption.

Leveraging real-world Data from administrative claims and medical records to inform safety and effectiveness of piperacillin-tazobactam in the Management of Pediatric Hospital Acquired Pneumonia.

Pediatric-specific safety data are required during development of pharmaceutical agents. Retrospective studies can leverage real-world data to assess safety and effectiveness in children where prospective, controlled studies are not feasible. A retrospective cohort study combined data from Pediatric Health Information Systems (PHIS) and medical records to evaluate the safety and effectiveness of piperacillin/tazobactam (P/T) in pediatric patients with hospital-acquired pneumonia (HAP). After identifying 407 patients diagnosed with HAP receiving P/T (n=140) or Comparator (n=267) HAP-appropriate antibiotics between 2003-2016 across seven pediatric institutions, we evaluated comparative risk of a serious adverse event (SAE). Clinical improvement 14 days after therapy initiation was studied as a secondary outcome. Incidence rate ratios (IRRs) were calculated to compare between exposure groups using inverse probability-weighted Poisson regression models. The unadjusted and adjusted IRRs with 95% CIs for SAEs were 1.26(0.66-2.39) and 1.24(0.65-2.35). The unadjusted and adjusted ORs with 95% CIs for clinical improvement were 1.14(0.56-2.34) and 1.50(0.67-3.38). Point estimates from this retrospective analysis suggest similar safety and clinical effectiveness of P/T and comparator antibiotics for treating HAP. However, due to wide CIs, actual between-group differences cannot be excluded. Existing real-world data can be utilized to inform pediatric-specific safety and effectiveness of medications used in off-label settings.

The UT Health Living Room: Expanding the Psychiatric Crisis Continuum of Care.

Traditional forms of psychiatric crisis treatment increasingly are being buttressed by services along the Psychiatric Crisis Continuum of Care, such as short-term crisis stabilization services and peer crisis services. The UT Health Living Room (LR) is an outpatient crisis counseling service that adds three promising elements to the Continuum: (1) it integrates outpatient treatment plans into crisis counseling, (2) provides care in a space and with staff who are familiar to patients, and (3) provides training in evidence-based crisis intervention. We examined two-year LR feasibility and outcome data. Mixed-method analyses used longitudinal clinic data and patient self-report measures. Results provide initial support for the feasibility, cost effectiveness and clinical effectiveness of the LR. Limitations include non-blinded ratings, limited experimental control, and simple cost-effectiveness methodology. The UT Living Room is feasible and offers novel elements to help patients in community clinics address emotional crises.