Tag: statistics

JAMA Dermatol. 2023 Jan 11. doi: 10.1001/jamadermatol.2022.5534. Online ahead of print.

ABSTRACT

IMPORTANCE: Lebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials.

OBJECTIVE: To evaluate efficacy and safety of LEB combined with low- to mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD.

DESIGN, SETTING, AND PARTICIPANTS: The ADhere trial was a 16-week randomized, double-blinded, placebo (PBO)-controlled, multicenter, phase 3 clinical trial conducted from February 3, 2020, to September 16, 2021. The study was conducted at 54 outpatient sites across Germany, Poland, Canada, and the US and included adolescent (aged ≥12 to <18 years weighing ≥40 kg) and adult patients with moderate-to-severe AD. The treatment allocation ratio was 2:1 (LEB:PBO).

INTERVENTIONS: Overall, 211 patients were randomized to subcutaneous LEB (loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks [Q2W] thereafter) or PBO Q2W in combination with TCS for 16 weeks.

MAIN OUTCOMES AND MEASURES: Efficacy analyses at week 16 included proportions of patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA [0,1]) with 2 or more points improvement from baseline, and 75% improvement in the Eczema Area and Severity Index (EASI-75). Key secondary end points included evaluation of itch, itch interference on sleep, and quality of life. Safety assessments included monitoring adverse events (AEs).

RESULTS: The mean (SD) age of patients was 37.2 (19.3) years, 103 (48.8%) patients were women, 31 (14.7%) patients were Asian, and 28 (13.3%) patients were Black/African American. At week 16, IGA (0,1) was achieved by 145 (41.2%) patients in the LEB+TCS group vs 66 (22.1%) receiving PBO+TCS (P = .01); corresponding proportions of patients achieving EASI-75 were 69.5% vs 42.2% (P < .001). The LEB+TCS group showed statistically significant improvements in all key secondary end points. Most treatment-emergent adverse events (TEAEs) were nonserious, mild or moderate in severity, and did not lead to study discontinuation. The TEAEs frequently reported in the LEB+TCS group included conjunctivitis (7 [4.8%]), headache (7 [4.8%]), hypertension (4 [2.8%]), injection site reactions (4 [2.8%]), and herpes infection (5 [3.4%]) vs 1.5% or less patient-reported frequencies in the PBO+TCS group. Similar frequencies of patient-reported serious AEs following LEB+TCS (n = 2, 1.4%) and PBO+TCS (n = 1, 1.5%).

CONCLUSIONS AND RELEVANCE: In this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04250337.

PMID:36630140 | DOI:10.1001/jamadermatol.2022.5534

JAMA Netw Open. 2023 Jan 3;6(1):e2250416. doi: 10.1001/jamanetworkopen.2022.50416.

ABSTRACT

IMPORTANCE: As the field of medicine strives for equity in care, research showing the association of social determinants of health (SDOH) with poorer health care outcomes is needed to better inform quality improvement strategies.

OBJECTIVE: To evaluate the association of SDOH with prostate cancer-specific mortality (PCSM) and overall survival (OS) among Black and White patients with prostate cancer.

DATA SOURCES: A MEDLINE search was performed of prostate cancer comparative effectiveness research from January 1, 1960, to June 5, 2020.

STUDY SELECTION: Two authors independently selected studies conducted among patients within the United States and performed comparative outcome analysis between Black and White patients. Studies were required to report time-to-event outcomes. A total of 251 studies were identified for review.

DATA EXTRACTION AND SYNTHESIS: Three authors independently screened and extracted data. End point meta-analyses were performed using both fixed-effects and random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed, and 2 authors independently reviewed all steps. All conflicts were resolved by consensus.

MAIN OUTCOMES AND MEASURES: The primary outcome was PCSM, and the secondary outcome was OS. With the US Department of Health and Human Services Healthy People 2030 initiative, an SDOH scoring system was incorporated to evaluate the association of SDOH with the predefined end points. The covariables included in the scoring system were age, comorbidities, insurance status, income status, extent of disease, geography, standardized treatment, and equitable and harmonized insurance benefits. The scoring system was discretized into 3 categories: high (≥10 points), intermediate (5-9 points), and low (<5 points).

RESULTS: The 47 studies identified comprised 1 019 908 patients (176 028 Black men and 843 880 White men; median age, 66.4 years [IQR, 64.8-69.0 years]). The median follow-up was 66.0 months (IQR, 41.5-91.4 months). Pooled estimates found no statistically significant difference in PCSM for Black patients compared with White patients (hazard ratio [HR], 1.08 [95% CI, 0.99-1.19]; P = .08); results were similar for OS (HR, 1.01 [95% CI, 0.95-1.07]; P = .68). There was a significant race-SDOH interaction for both PCSM (regression coefficient, -0.041 [95% CI, -0.059 to 0.023]; P < .001) and OS (meta-regression coefficient, -0.017 [95% CI, -0.033 to -0.002]; P = .03). In studies with minimal accounting for SDOH (<5-point score), Black patients had significantly higher PCSM compared with White patients (HR, 1.29; 95% CI, 1.17-1.41; P < .001). In studies with greater accounting for SDOH variables (≥10-point score), PCSM was significantly lower among Black patients compared with White patients (HR, 0.86; 95% CI, 0.77-0.96; P = .02).

CONCLUSIONS AND RELEVANCE: The findings of this meta-analysis suggest that there is a significant interaction between race and SDOH with respect to PCSM and OS among men with prostate cancer. Incorporating SDOH variables into data collection and analyses are vital to developing strategies for achieving equity.

PMID:36630135 | DOI:10.1001/jamanetworkopen.2022.50416

Arch Physiol Biochem. 2023 Jan 11:1-16. doi: 10.1080/13813455.2022.2163260. Online ahead of print.

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a serious endocrine and metabolic disease that is highly prevalent and causes high mortality and morbidity rates worldwide. This review aims to focus on the potential of probiotics in the management of T2DM and its complications and to summarise the various mechanisms of action of probiotics with respect to T2DM. In this review, experimental studies conducted between 2016 and 2022 were explored. The possible mechanisms of action are based on their ability to modulate the gut microbiota, boost the production of short-chain fatty acids (SCFAs) and glucagon-like peptides, inhibit α-glucosidase, elevate sirtuin 1 (SIRT1) levels while reducing fetuin-A levels, and regulate the level of inflammatory cytokines. This review recommends carrying out further studies, especially human trials, to provide robust evidence-based knowledge on the use of probiotics for the treatment of T2DM.IMPACT STATEMENTT2DM is prevalent worldwide causing high rates of morbidity and mortality.Gut microbiota play a significant role in the pathogenesis of T2DM.Probiotics can be used as possible therapeutic tools for the management of T2DM.The possible mechanisms of action of probiotics include modulation of the gut microbiota, production of SCFAs and glucagon-like peptides, inhibition of α-glucosidase, raising SIRT1, reducing fetuin-A levels, and regulating the level of inflammatory cytokines.

PMID:36630122 | DOI:10.1080/13813455.2022.2163260

J Wound Care. 2023 Jan 2;32(1):29-34. doi: 10.12968/jowc.2023.32.1.29.

ABSTRACT

OBJECTIVE: With an ageing population and a rising number of people with chronic conditions and disabilities, pressure ulcers (PUs) are a frequent problem. Prevention and treatment, especially targeted at older people, frail and non-self-sufficient patients, are central to care provided by nurses. The objective of this study is to establish the incidence of PUs in hospital inpatients and identify possible associated risk factors.

METHOD: A clinical observational study was conducted from May to November 2019 in a sample of patients admitted to Azienda Sociosanitaria Ligure 2 in Italy. Clinical and sociodemographic data were collected at admission and at discharge, through a questionnaire or collection card. The analysis was done using SAS 9.4 2017 software.

RESULTS: In 7% of the 515 participating patients, PUs occurred during hospitalisation; PUs at stages I and II were predominantly in the coccyx, heels and malleolus.

CONCLUSION: Significant associations were found between the development of lesions and age, certain pathologies, the degree of patient autonomy and the level of skin integrity.

PMID:36630116 | DOI:10.12968/jowc.2023.32.1.29

In Vitro Cell Dev Biol Anim. 2023 Jan 11. doi: 10.1007/s11626-022-00743-1. Online ahead of print.

ABSTRACT

Mitochondrial dysfunction is a fundamental mechanism leading to drug nephrotoxicity, such as gentamicin-induced nephrotoxicity. Mitochondrial therapy (mitotherapy) or exogenous mitochondria transplantation is a method that can be used to replace dysfunctional mitochondria with healthy mitochondria. This method can help in the treatment of diseases related to mitochondria. In this research, we studied the transplantation effect of freshly isolated mitochondria on the toxicity induced by gentamicin on renal proximal tubular cells (RPTCs). Furthermore, possible gender-related effects on supplying exogenous rat kidney mitochondria on gentamicin-induced RPTCs were investigated. At first, the normality and proper functioning of fresh mitochondria were assessed by measuring mitochondrial succinate dehydrogenase activity (SDH) and changes in mitochondrial membrane potential (MMP). Then, the protective effects of mitochondrial transplantation against gentamicin-induced mitochondrial toxicity were evaluated through parameters including lactate dehydrogenase (LDH) leakiness, reactive oxygen species (ROS) production, lipid peroxidation (LPO) content, reduced glutathione (GSH) level, extracellular oxidized glutathione (GSSG) level, ATP level, MMP collapse, and caspase-3 activity. According to the statistical analysis, transplanting the healthy mitochondria decreased the cytotoxicity, ROS production, MMP collapse, LPO content, GSSG levels, and caspase-3 activity caused by gentamicin in RPTCs. Also, it has caused an increase in the level of ATP and GSH in the RPTCs. Furthermore, higher preventive effects were observed for the female group. According to the current study, mitochondrial transplantation is a potent therapeutic method in xenobiotic-caused nephrotoxicity.

PMID:36630058 | DOI:10.1007/s11626-022-00743-1

Obes Surg. 2023 Jan 11. doi: 10.1007/s11695-022-06441-x. Online ahead of print.

ABSTRACT

BACKGROUND: Silastic ring vertical gastroplasty (SRVG) and vertical banded gastroplasty (VBG) are associated with a high failure rate due to weight regain and complications at long-term follow-up. Consequently, surgical correction for such procedures is warranted. Controversy exists as to which surgical procedure is the ideal choice for such correction. Our aim is to compare short-term outcome of Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) repair for failed VBG/SRVG bariatric procedures.

METHODS: The medical records of patients with failed SRVG who underwent corrective procedures at our institute between 2004 and 2018 were retrospectively reviewed. Patients characteristics, surgical approaches, and intraoperative and post-operative complications were examined and compared.

RESULTS: Sixty patients in total underwent a surgical corrective procedure for failed SRVG. Thirty-one patients underwent RYGB, and 29 patients underwent BPD. Major complications were seen more in the RYGB group (35% = 11) compared to the BPD (6.9% = 2). Even though anastomotic leak rates were not statistically significant (p = 0.053), an apparent tendency for such a complication was noted in the RYGB group. RYGB procedure had an increased 30-day complication rate (p = 0.055) compared to RYGB. Laparoscopic approach had statistically fewer complications than open approach. No mortality was observed in either group.

CONCLUSION: Our study showed that BPD is a safe option with less complication rates than RYGB in the short-term period for surgical correction of failed VBG/SRVG procedures.

PMID:36630053 | DOI:10.1007/s11695-022-06441-x

Environ Sci Pollut Res Int. 2023 Jan 11. doi: 10.1007/s11356-023-25166-7. Online ahead of print.

ABSTRACT

Rapid urbanization improves socioeconomic development but challenges ecosystem sustainability. Meanwhile, the gradient responses of ecosystem services (ESs) to landscape structures and associated regime shifts of the agriculture-ecosystem-economy nexus (AEEN) have not been sufficiently addressed, preventing an effective balance between socioeconomic prosperity and ecosystem conservation. To bridge this knowledge gap, this study selected the Guangdong Province of southeastern China to explore landscape dynamics from 1985 to 2020 and their spatially heterogeneous impacts on ESs and the AEEN, based on Integrated Valuation of Ecosystem Services and Trade-offs approach and other biophysical models as well as statistical records about socioeconomic factors. AEEN elements, including ESs, responded directly to policy adjustments in terms of ecosystem restoration and landscape management and presented remarkable regime shifts (i.e., phase changes) and spatial heterogeneity. Aggressive agricultural reclamation before 1999 increased crop productivity but caused vegetation degradation and biomass decline. Accelerated urban expansion and ecosystem restoration efforts have improved economic and ecological benefits but have substantially reduced crop productivity and threatened food security. However, timely policy adjustments since 2009 reversed the declining trend and maintained the grain supply. Landscape composition presented patterns of gradual decline along the urban-rural gradient, which in turn determined ES gradient patterns. For instance, water yield and nitrogen export positively correlated with each other (p < 0.0001) but negatively correlated with other ESs. Our study enriches the understandings of social-ecological systems’ response to man-made interventions from AEEN perspective allowing for spatial variabilities and regime shifts, which support policy formulation for coordinating ecological and economic benefits.

PMID:36630037 | DOI:10.1007/s11356-023-25166-7

Breast Cancer. 2023 Jan 11. doi: 10.1007/s12282-022-01427-0. Online ahead of print.

ABSTRACT

BACKGROUND: More than 10% of HER2-positive metastatic breast cancer (mBC) will develop Central Nervous System (CNS) metastases as first and isolated site of relapse on trastuzumab and pertuzumab first-line therapy. However, few clinical data are available to guide the best strategy in this setting.

METHODS: Patients experiencing isolated CNS progression on trastuzumab and pertuzumab first-line therapy were retrospectively identified from the French Epidemiological Strategy and Medical Economics (ESME) real-life database between 2008 and 2016.

RESULTS: Among 995 patients treated with first-line trastuzumab and pertuzumab for HER2-positive mBC, 132 patients (13%) experienced isolated CNS progression with a median time of 12 months after mBC diagnosis. Twelves patients did not receive any treatment and were excluded from the analysis. Among the 120 patients considered, 76 (63%) received CNS-directed local therapy, 73 (60%) continued trastuzumab and pertuzumab, whereas 47 (39%) started another systemic treatment. After a median follow-up of 21 months, there was no difference in progression-free survival for patient who continued trastuzumab-pertuzumab or switched to another systemic treatment. In multivariate analysis, trastuzumab-pertuzumab continuation was associated with longer OS (HR 0,28 IC 95%: 0,14-0,54 p < 0,001). mOS was not reached (95% 37.6-NE) and was 23.2 months (95% CI 15.5-53.6) in patients who continued trastuzumab and pertuzumab therapy and in patients who switched for another systemic therapy, respectively.

CONCLUSION: In this real-life cohort, trastuzumab-pertuzumab continuation after local treatment for isolated CNS progression did not negatively impact PFS and OS. Prospective trials and assessment of new strategies are warranted in this specific situation.

PMID:36630013 | DOI:10.1007/s12282-022-01427-0

Insights Imaging. 2023 Jan 11;14(1):7. doi: 10.1186/s13244-022-01357-7.

ABSTRACT

BACKGROUND: Poor glycemic control is associated with left ventricular (LV) dysfunction in patients with type 2 diabetes mellitus (T2DM). Nonetheless, the association between glycemic control and right ventricular (RV) function in T2DM has not been studied. This study aimed to evaluate the correlation between glycemic control and biventricular function and assess whether one ventricular function was mediated by the other ventricular changes using cardiac magnetic resonance.

MATERIALS AND METHODS: A total of 91 T2DM patients with normal ejection fraction were enrolled and divided into two groups according to glycated hemoglobin (HbA1c) with a cut off 7%. Twenty controls were included. Biventricular ventricular strain parameters, including global peak systolic radial strain, global peak systolic circumferential strain (GCS), global peak systolic longitudinal strain (GLS), peak diastolic radial strain rate (RSR), peak diastolic circumferential strain rate (CSR) and peak diastolic longitudinal strain rate (LSR) were measured.

RESULTS: Compared with controls, patients with both HbA1c < 7% and HbA1c ≥ 7% showed significantly lower LVGCS, LVGLS, LVCSR, LVLSR, RVGLS, RVRSR, RVCSR and RVLSR. Patients with HbA1c ≥ 7% elicited significantly higher RVGCS than controls and lower LVGLS, LVCSR, LVLSR, RVGLS and RVLSR. Multivariable linear regression demonstrated that HbA1c was independently associated with LVGLS, LVLSR, RVGLS and RVLSR after adjustment for traditional risk factors. LV (RV) was not statistically mediated by the other ventricular alterations.

CONCLUSION: In T2DM patients, glycemic control was independently associated with impaired LV and RV systolic and diastolic function and these associations were not mediated by the other ventricular changes.

PMID:36630007 | DOI:10.1186/s13244-022-01357-7

J Nephrol. 2023 Jan 11. doi: 10.1007/s40620-022-01530-7. Online ahead of print.

ABSTRACT

INTRODUCTION: The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown.

METHODS: Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up.

RESULTS: After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52-4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52-4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99-73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18-3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63-2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m² greater in the aliskiren group (12.83 vs 5.08; 95% CI – 0.17 to 15.66; P = 0.055).

CONCLUSION: Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.

PMID:36630006 | DOI:10.1007/s40620-022-01530-7