Two-cohort Study Research Articles

Envafolimab in combination with lenvatinib and albumin paclitaxel for previously treated advanced GEJ adenocarcinoma: Latest analysis of a phase II, two-cohort study.

375 Background: The combination of first-line chemotherapy and PD-1 has emerged as a standard treatment, enhancing the efficacy in advanced gastric/gastroesophageal junction (GEJ) cancer. The efficacy of the combination of second-line chemotherapy and PD-1/PD-L1 remains unclear. This study aims to observe the efficacy of Envafolimab (PD-L1 inhibitor ) plus tyrosine kinase inhibitors (TKIs) and second-line chemotherapy in the treatment of patients (pts) with advanced GEJ adenocarcinoma. Methods: Eligible pts with HER2-negative, microsatellite stable (MSS), advanced GEJ adenocarcinoma were enrolled in this study. Pts who never received PD-1 or PD-L1 inhibitors before would assign into Group A. Pts in Group B have failed first-line PD-1 antibody combined chemotherapy, with optimal efficacy as or above stable disease (SD). Pts in both groups received Envafolimab (200mg, hypodermic injection, days 1, 15, Q4W) combined with Lenvatinib (8mg/12mg, po, once a day) and albumin paclitaxel (100mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or pts refusal to continue treatment. The primary endpoint was objective response rate(ORR) per iRECISTv1.1, and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: From Oct 2022 to Apr 2024, 32 pts were enrolled. Both groups enrolled 16 pts equally, and 15 pts of each group were evaluable for efficacy analysis. The average ages were 60.07 ± 11.73 y and 50.13 ± 12.18 y in group A and B respectively. In group A, 7 pts had been tested for PD-L1 status, of which 2 (13.3%) was positive and 5 (33.3%) were negative. PD-L1 status was negative in 5(33.3%) pts, positive in 9 (60.0%), and untested in 1(6.7%) in group B. As of Sep 14, 2024, The ORR was 60.0% (9/15) in group A and 46.7% (7/15) in group B. The DCR was 100.0% (15/15) in both groups. After a median follow-up of 17.0 mo (IQR: 8.0-18.8) in group A, the mPFS was 8.2 mo (95% CI = 6.1-10.4), and the mOS was 14.8 mo(95% CI = 7.4-22.2). With median follow-up of 9.0 mo (IQR: 6.1-16.2) in group B, the mPFS was 5.9 mo (95% CI= 3.8-8.1) and the mOS was 11.5 mo (95% CI = 3.1-19.9). Overall incidences of adverse events (AEs) of any grade was 100% (30/30), and 80.0% (24/30) pts had ≥ grade 3 AEs during treatment. Most treatment-related adverse events (TRAEs) of grade ≥3 included decreased neutrophil count (73.3%), decreased leukocyte count (63.33%), Anemia (10%), febrile neutropenia (6.67%). Conclusions: In pts of advanced gastric cancer who have previously received PD-1 inhibitors or not, this second-line combination therapy demonstrates promising preliminary effects. Pts who have not previously received ICIs might benefit more from this combination therapy. Clinical trial information: NCT06030934 .

Association between adolescent obesity and early adulthood healthcare utilization—a two-cohort prospective study

BackgroundPediatric obesity is a growing global health challenge, with long-term implications for individuals and healthcare systems. Existing studies on the association between pediatric obesity and healthcare use in adulthood are limited and often rely on mathematical simulation models. This study aims to provide real-world data on the impact of adolescent obesity on specialized healthcare utilization and costs in early adulthood.MethodsThis study analyzed data from two longitudinal cohorts: a population-based cohort from Norway (Young-HUNT) and a clinical cohort from Sweden (BORIS), the latter with matched general population comparators. Individuals included were born between 1987 and 1994, with BMI measurements at ages 13–19, and follow-up data from ages 20 to 30 years. Healthcare utilization and costs were assessed using national patient registries.ResultsA total of 7592 individuals from Norway (5.7% with adolescent obesity) and 1543 individuals from Sweden with adolescent obesity, accompanied with 7330 matched general population comparators, were included. Among females, adolescent obesity was associated with significantly higher specialized healthcare utilization and costs in young adulthood, e.g., in Sweden, females with adolescent obesity had a 57% probability of annual specialized healthcare visits at ages 25–29, compared to 49% among the general population, p < 0.0001. In Norway, a similar pattern was observed. Among males, the association between obesity and healthcare utilization/annual specialized visits was less prominent. Annual excess costs for females with a history of adolescent obesity ranged from €578 to €835, while males showed minimal or no annual excess costs.ConclusionsAnalyses of real-world data cohorts from Norway and Sweden reveal that adolescent obesity is associated with increased healthcare utilization and costs in young adulthood, exceeding previous estimates. A distinct sex difference was evident, with females incurring higher costs compared to males.

Nutritional Status in Locally Advanced or Metastatic Solid Cancer Patients Treated With Chemotherapy, Radiotherapy, and Immunotherapy in Spanish Outpatient Oncology Units.

Malnutrition is a prevalent condition in cancer patients that significantly impacts patients' clinical outcomes and health-related quality of life (HR-QoL). The outcome was to characterize the nutritional status by describing the prevalence of malnutrition (mild, moderate, or severe) and its risk in outpatient cancer patients. Multicenter, prospective, cross-sectional, descriptive, two-cohort study conducted on consecutive adult patients with locally advanced or metastatic solid tumors (stages III-IV). The study was conducted in 10 Spanish hospitals distributed all over the Spanish geography, with a recruitment period of 5 months (between April and September 2020). Study patients were divided into two groups according to their cancer therapy: group A, patients who underwent immunotherapy, and group B, patients who received combined therapy (immunotherapy plus chemotherapy and radiotherapy). A total of 585 patients were included. The proportion of patients at risk of malnutrition was notably more significant in the combination group (chemotherapy and/or radiotherapy) than in the immunotherapy-only group (28.3% versus 58.5%, respectively, P < .0001). According to this evaluation the highest proportion of patients at risk were those with pancreatic cancer (51 patients; 89.5%), followed by large intestine cancer (52 patients; 55.3%) and lung cancer (56 patients; 29.3%), P < .0001. Patients treated with only immunotherapy seemed to have better nutritional status, which indicated health-related quality of life improvement. Additionally, there was a trend associating nutritional status with tumor location. Treatment strategy, treatment duration, performance status, and treatment location were independently associated with malnutrition. Integrating nutritional assessment into routine clinical practice will improve the quality of life of oncology patients. An integrative approach to health improves overall results in terms of nutritional status and improved quality of life and shows that daily living activities are more satisfactory for patients with nursing interventions. Nursing interventions are consistent with an educational approach to patients as long as the interventions described in international guidelines are detailed in the framework of the patient care.

The risk of diabetes and HbA1c deterioration during antipsychotic drug treatment: A Danish two-cohort study among patients with first-episode schizophrenia.

Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c). We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before. In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication. This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES.

Envafolimab in combination with lenvatinib and albumin paclitaxel for previously treated advanced gastric/gastroesophageal junction adenocarcinoma: Preliminary analysis of a phase II, two-cohort study.

e16039 Background: The combination of first-line chemotherapy and PD-1 has emerged as a standard treatment, enhancing the efficacy in advanced gastric/gastroesophageal junction (GEJ) cancer. The efficacy of the combination of second-line chemotherapy and PD-1/PD-L1 remains unclear. This study aims to observe the efficacy of Envafolimab plus tyrosine kinase inhibitors (TKIs) and second-line chemotherapy in the treatment of patients with advanced GEJ adenocarcinoma. Methods: This prospective, open-label, phaseⅡ, two cohort study was conducted to assess the efficacy and safety of Envafolimab-based therapy in patients experiencing progression after initial first-line treatment. Eligible patients with HER2-negative, microsatellite stable (MSS), advanced GEJ adenocarcinoma were consecutively enrolled and assigned into cohort A or cohort B, according to whether they received PD-1 inhibitors in the first-line treatment. Patients in both cohorts received Envafolimab (200mg, hypodermic injection, days 1 and 15, Q4W) combined with Lenvatinib (8mg/12mg, po, once a day) and albumin paclitaxel (100mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or patients refusal to continue treatment. The primary endpoint was objective response rate(ORR) per iRECIST v1.1, and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. The efficacy and safety data in this analysis were from patients in cohort A who previously failed in first-line chemotherapy and did not receive PD-1 or PD-L1 inhibitors ever. Results: From October 2022 to June 2023, cohort A enrolled 16 patients, and 15 of them were evaluable for efficacy analysis. The average age was 58.87 ±11.81 years, 80% patients were male. 6 patients had been tested for PD-L1 status, of which 1 (16.7%) was positive and 5 (83.3%) were negative. As of Jan29, 2024, the median follow-up was 10.6 months (95%CI = 8.67-12.53), the median number of treatment cycles was 7 cycles (IQR: 5, 8). Based on the iRECIST v1.1, the ORR was 60.00% (90% CI = 35.96%-80.91%), the DCR was 100.00% (90% CI = 81.90%-100.00%). The median PFS (mPFS) was 8.23 months (90% CI =6.27-8.61), and the median OS (mOS) was 10.6 months (90% CI =8.79-12.15). Overall incidences of adverse events (AEs) of any grade was 100%, and 75.00% (n = 12) had ≥ grade 3 AEs during treatment. Most treatment-related adverse events (TRAEs) of grade ≥3 included neutrophil count (56.25%), decreased leukocyte count (37.5%). Conclusions: In patients of advanced gastric cancer who have not previously received PD-1/PD-L1 inhibitors, this second-line combination therapy demonstrates promising preliminary effects. Clinical trial information: NCT06030934 .

TTCC-2022-01: Niraparib and dostarlimab in locally-advanced head and neck squamous cell carcinoma treated with (chemo) radiotherapy (RADIAN).

TPS6125 Background: The prognosis of locally-advanced head and neck squamous cell carcinoma (LA-HNSCC) remains poor, with a 60% 5-year overall survival (OS) rate despite curative-intent therapies. Treatment intensification strategies with antiPD-(L)1 agents given concurrently to (chemo)radiotherapy (CRT) have failed to improve survival. New radiosensitizing agents such as PARP inhibitors have shown encouraging results in early studies, and are of special interest in cisplatin-unfit patients (pts) (Moutafi et al. 2021). Beyond radiation sensitization, PARP inhibition is predicted to trigger immune responses via STING pathway activation, and synergize with anti-PD-(L)1 agents (Sen T et al., 2019). We hypothesize that niraparib will enhance antitumor immune responses when combined with dostarlimab before and after definitive CRT and will boost RT response ultimately leading to higher disease-free survival (DFS). Methods: Trial design: RADIAN is an investigator-initiated, multi-center, non-randomized two-cohort phase 1b study of niraparib and dostarlimab in LA-HNSCC pts candidates for CRT (cohort A) or RT alone (cohort B – cisplatin unfit). Dostarlimab 500mg is given intravenously 3 weeks(w) before RT and then q/3w starting w4 post-RT for up to 14 cycles. Niraparib 200 or 300mg is given orally once daily 1w after dostarlimab until start of CRT (cohort A) or continuously until last dose of RT (Cohort B) and then continuously in 3w cycles from w4 post-RT for up to a year (14 cycles). Intensity-modulated RT (70 Grays:2Gray/fraction) and high-dose cisplatin are given as per standard-of-care. Study procedures include collection of baseline archival or fresh tumor sample for molecular profiling, PD-L1 expression and immunophenotyping; serial blood samples for circulating tumor (ct) DNA and clinical/endoscopic photographs of the tumor (baseline, pre-niraparib, pre-RT, 12w post-RT, end-of treatment, and at progression). Imaging and follow-up procedures are conducted as per standard-of-care. Key eligibility criteria: untreated, stage III to IVB laryngeal, hypopharyngeal, HPV-negative oropharyngeal SCC (stage III only if HPV-positive), and stage IVB oral cavity SCC as per TNM 8th edition;adequate organ function; no autoimmune disorders; no immunosuppressive therapy. Study objectives: primary objective is to evaluate 1-year disease free survival. Secondary objectives: safety/tolerability including RT delay/completion; locoregional and distant control, event-free survival, OS and ctDNA dynamics correlation with efficacy endpoints. Sample size: 32 evaluable pts for correlative studies are planned for enrollment (16/cohort). It is expected that experimental treatment will provide an increase of efficacy of 0.64 in terms of HR (1-year DFS of 75.9 % in cohort A and 68.2% in cohort B). Study activation: Nov 11th 2023, with 2 pts enrolled as of Feb 6th 2024. Clinical trial information: NCT05784012 .

Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder

Abstract Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson’s disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43–87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1–3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson’s disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio &amp;lt; 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson’s disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson’s disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson’s disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.

Assessing the Feasibility of a Two-Cohort Design to Assess the Potential of Homeopathic Medicinal Products to Reduce Antimicrobial Resistance in Turkeys (The HOMAMR Project)-Study Protocol.

Antimicrobial resistance (AMR) is a serious public health concern worldwide. The European Union requires a reduction in the use of antibiotics by 50% by 2030, with separate regulations on organic production that give preference to homeopathy and phytotherapy in organic farms before the use of conventional medicines (including antibiotics). We have therefore designed a two-phased project whose overarching aim is to investigate the potential role of homeopathic medicinal products (HMPs) in combating AMR in turkeys (the HOMAMR project): a two-cohort feasibility study using turkey-farm data that have been collected and analyzed retrospectively, followed by a prospective two-cohort study in turkey farms that would examine the impact of HMPs on changing antibiotic use. The objective of this paper is to describe the protocol for the first phase of HOMAMR, which is a study under field conditions to assess the feasibility of collecting data retrospectively about turkeys that have been managed conventionally only or with HMPs. Surveys performed on farms in Germany and Austria, including interviews with consenting farmers, will determine the feasibility of comparing retrospectively gathered data on antibiotic use and performance/production data in two cohorts of turkeys: (1) homeopathic treatment with conventional care (antibiotics) added if necessary or (2) conventional care (antibiotics) only. Co-primary outcomes to be studied are the amount of antimicrobial use and production period-related mortality. In addition, other production/performance parameters will be compared between the two treated cohorts. To our knowledge, this is the first feasibility study on the treatment of turkeys using homeopathy, and whose retrospectively obtained data will inform a prospective study that would examine the impact of HMPs on antibiotic use in commercial turkey raising, fattening and breeding production.

Depression, Anxiety, and Stress Among Emerging Adult Undergraduates: A Longitudinal and Two-Cohort Study.

Mental disorders constitute one of the population's principal health problems, especially among undergraduates. This quantitative study compared levels of depression, anxiety, and stress in a sample of emerging adult university undergraduates from a gender perspective (1) during the initial and intermediate years of emerging adulthood and (2) in two different cohorts. A total of 383 Spanish emerging adult university undergraduates were monitored longitudinally (2015-2018) and two cohorts were compared (2015-2020). Participants completed the validated Spanish version of the Depression Anxiety Stress Scale-21. Mean-level and rank-order stability was found across the two waves of the longitudinal study in relation to levels of depression, anxiety, and stress. Significant differences were found between the two cohorts, indicating higher levels of psychological distress in 2020 than in 2015. Women were found to have higher levels of psychological distress, particularly stress, than men in both waves and cohorts. Results are discussed in relation to the negative effects of the COVID-19 health crisis on the emotional health of emerging adults. The present study highlights the need to establish measures designed to improve the mental health of emerging adults, which was more severely affected by the COVID-19 crisis than by the aftermath of the 2008 financial crisis. It also underscores the need to develop interventions designed to alleviate the greater degree of stress suffered by women.

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds.

Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24h; u24LH = 0.035 or 0.08 IU/24h). The combination of u24FSH > 1.1 IU/24h and u24LH > 0.08 IU/24h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. No specific funding was used. All authors declared no conflict of interest. In-house #23-5214 registered study.

Developmental origins of psycho-cardiometabolic multimorbidity in adolescence and their underlying pathways through methylation markers: a two-cohort study.

Understanding the biological mechanisms behind multimorbidity patterns in adolescence is important as they may act as intermediary risk factor for long-term health. We aimed to explore relationship between prenatal exposures and adolescent's psycho-cardiometabolic intermediary traits mediated through epigenetic biomarkers, using structural equation modeling (SEM). We used data from mother-child dyads from pregnancy and adolescents at 16-17years from two prospective cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) and Raine Study from Australia. Factor analysis was applied to generate two different latent factor structures: (a) prenatal exposures and (b) adolescence psycho-cardiometabolic intermediary traits. Furthermore, three types of epigenetic biomarkers were included: (1) DNA methylation score for maternal smoking during pregnancy (DNAmMSS), (2) DNAm age estimate PhenoAge and (3) DNAm estimate for telomere length (DNAmTL). Similar factor structure was observed between both cohorts yielding three prenatal factors, namely BMI (Body Mass Index), SOP (Socio-Obstetric-Profile), and Lifestyle, and four adolescent factors: Anthropometric, Insulin-Triglycerides, Blood Pressure, and Mental health. In the SEM pathways, stronger direct effects of F1prenatal-BMI (NFBC1986=β: 0.27; Raine=β: 0.39) and F2prenatal-SOP (β: -0.11) factors were observed on adolescent psycho-cardiometabolic multimorbidity. We observed an indirect effect of prenatal latent factors through epigenetic markers on a psycho-cardiometabolic multimorbidity factor in Raine study (P<0.05). The present study exemplifies an evidence-based approach in two different birth cohorts to demonstrate similar composite structure of prenatal exposures and psycho-cardiometabolic traits (despite cultural, social, and genetic differences) and a common plausible pathway between them through underlying epigenetic markers.

Rezvilutamide in combination with androgen-deprivation therapy, with or without salvage radiotherapy, for patients experiencing biochemical recurrence following radical prostatectomy: A multi-center, open-label, two-cohort study.

Rezvilutamide in combination with androgen-deprivation therapy, with or without salvage radiotherapy, for patients experiencing biochemical recurrence following radical prostatectomy: A multi-center, open-label, two-cohort study.

Population trajectories and age-dependent associations of obesity risk factors with body mass index from childhood to adolescence across European regions: A two-cohort study.

To investigate population trajectories of behavioural risk factors of obesity from childhood to adolescence and their associations with body mass index (BMI) in children across European regions. Data were harmonised between the European multi-centre IDEFICS/I.Family and the Amsterdam Born Children and their Development Cohort. Participants were aged 2.0-9.9 and 5.0-7.5 years at baseline, respectively, and were followed until age 18 years. Behavioural risk factors of interest included diet, physical activity, media use and sleep. Mixed effects models were used for statistical analyses to account for repeated measurements taken from the same child. The study included a total of 14 328 individuals: 4114, 4582, 3220 and 2412 participants from Northern, Southern, Eastern Europe and Amsterdam, respectively. Risk factor means and prevalences changed with age, but the trajectories were mostly similar across regions. Almost no associations between behavioural factors and BMI were found at the age of 6 years. At 11 years, daily sugar-sweetened foods consumption, use of active transport, sports club membership and longer nocturnal sleep duration were negatively associated with BMI in most regions; positive associations were found with media use. Most associations at 11 years of age persisted to 15 years. Whilst population trajectories of media use and nocturnal sleep duration are similar across European regions, those of other behavioural risk factors like active transport and daily vegetable consumption differ. Also, associations between behavioural risk factors and BMI become stronger with age and show similar patterns across regions.

Prehospital risk assessment and direct transfer to a percutaneous coronary intervention centre in suspected acute coronary syndrome

ObjectivePrehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to revascularisation, increased duration of...

Profiles of climate change distress and climate denialism during adolescence: A two-cohort longitudinal study

This study investigates adolescents’ climate change distress and climate denialism profiles with two cohorts (born in 2008 and 2006) using longitudinal data from two waves collected in 2020 and 2021 (N = 3,002). In addition, the explanatory similarity of the subgroups regarding general well-being and pro-environmental behavior was studied. Four profiles were identified. The largest group was named the normative-carefree group because they had low climate change distress and climate denialism. Another group named denialists also had low distress but higher denial. Both these groups were associated with relatively good well-being. The third group had elevated climate change-related emotional distress and low climate denial and was therefore named the emotionally involved group. They engaged in pro-environmental behavior the most. The last and the smallest group was called the overburdened because they had elevated distress accompanied by denial; belongingness to the group was related to low well-being. Estimated transition patterns showed that the profiles were unstable within a 1-year span. The results endorse that adolescents’ climate change distress is ongoing and developing all the time, rather than being something permanent. The results also show that both climate change distress and climate denialism can co-exist among adolescents.

A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength.

The gut microbiome affects the inflammatory environment through effects on T-cells, which influence the production of immune mediators and inflammatory cytokines that stimulate osteoclastogenesis and bone loss in mice. However, there are few large human studies of the gut microbiome and skeletal health. We investigated the association between the human gut microbiome and high resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia in two large cohorts; Framingham Heart Study (FHS [n=1227, age range: 32 - 89]), and the Osteoporosis in Men Study (MrOS [n=836, age range: 78 - 98]). Stool samples from study participants underwent amplification and sequencing of the V4 hypervariable region of the 16S rRNA gene. The resulting 16S rRNA sequencing data were processed separately for each cohort, with the DADA2 pipeline incorporated in the16S bioBakery workflow. Resulting amplicon sequence variants were assigned taxonomies using the SILVA reference database. Controlling for multiple covariates, we tested for associations between microbial taxa abundances and HR-pQCT measures using general linear models as implemented in microbiome multivariable association with linear model (MaAslin2). Abundance of 37 microbial genera in FHS, and 4 genera in MrOS, were associated with various skeletal measures (false discovery rate [FDR] ≤ 0.1) including the association of DTU089 with bone measures, which was independently replicated in the two cohorts. A meta-analysis of the taxa-bone associations further revealed (FDR ≤ 0.25) that greater abundances of the genera; Akkermansia and DTU089, were associated with lower radius total vBMD, and tibia cortical vBMD respectively. Conversely, higher abundances of the genera; Lachnospiraceae NK4A136 group, and Faecalibacterium were associated with greater tibia cortical vBMD. We also investigated functional capabilities of microbial taxa by testing for associations between predicted (based on 16S rRNA amplicon sequence data) metabolic pathways abundance and bone phenotypes in each cohort. While there were no concordant functional associations observed in both cohorts, a meta-analysis revealed 8 pathways including the super-pathway of histidine, purine, and pyrimidine biosynthesis, associated with bone measures of the tibia cortical compartment. In conclusion, our findings suggest that there is a link between the gut microbiome and skeletal metabolism.

TIPS-10 FEASIBILITY OF A MULTI-MODALITY CENTRAL NERVOUS SYSTEM SCREENING EVALUATION IN HER2+ BREASTCANCER PATIENTS

Abstract BACKGROUND Breast cancer is the most common cancer in the world and the second most common to metastasize to the central nervous system (CNS). CNS-metastases are the most common type of brain tumor and have a rising incidence. They are associated with neurologic morbidity and mortality and remain a major clinical challenge. Survival withCNS-metastases is short with a median survival in the order of months. The incidence of CNS-metastases is 5.1% in breast cancer however true prevalence is not known; at autopsy this incidence ranges between 20-40%. One contributing factor towards the development of CNS-metastases in breast cancer is HER2-positivity. Between 25%-48% of patients with HER2-positive metastatic breast cancer develop CNS-metastases. Currently, routine CNS surveillance imaging is not recommended, however guidelines suggest having a low threshold for evaluation with imaging and/or cerebrospinal fluid (CSF) analysis because of the high rate of CNS-metastases. The clinical relevance of occult CNS-metastases, survival after identification of occult CNS-metastases and the importance of earlier initiation of CNS therapy are unknown. Existing treatment strategies for CNS-metastases rely on a combinatorial approach of chemotherapy, radiotherapy and/or surgery which typically affords limited disease control. This trial seeks to study if surveillance imaging and CSF analysis are feasible as early disease detection mechanisms. METHODS This is a two-cohort study to establish feasibility of multi-modality CNS surveillance. Patients with HER2+ metastatic breast cancer patients (with no known CNS-metastases) who are either Stage IV (Cohort A) or Stage II/III are eligible (Cohort B). On study, patients will undergo MRI Brain and CSF analysis at 6 monthly intervals. CSF analysis includes cytology, circulating tumor cells and cell-free DNA analysis. We plan to enroll 20 patients (10 onto each cohort). 1 of 20 patients have enrolled. This is the first multi-modality screening feasibility study for patients HER2-positive breast cancer.

Experiences of childlessness and adoption in marriage among Basotho: A two-cohort phenomenological study

This article reports a two-cohort study conducted among adoptive parents in Maseru and Maputsoe Lesotho, in 2014 and 2019, with African research philosophy underpinning the study. The article reports data collected from 13 adoptive parents (eight parents in Cohort one and five parents in Cohort two) using in-depth interviews and later analysed through a six-step discourse analysis. In this regard, the role of elders in participants’ extended families were taken into account upon the study’s conceptualisation and implementation. The article focuses on participants’ reports of their experiences of both family childlessness and adoption. Women in Cohort one reported being abused by husbands and in-laws and excluded from family decisions. A woman in Cohort two reported being excluded from social activities by her erstwhile friend subsequent to adopting. From a phenomenological standpoint, the participants attributed their treatment from husbands, in-laws, and friends to their family childlessness and adoption that is happening in a Basotho socio-cultural environment where it is not the norm. &#x0D; How to reference using ASWNet style:&#x0D; Thabane S. (2023). Experiences of childlessness and adoption in marriage among Basotho: A two-cohort phenomenological study African Journal of Social Work, 13(3), 136-146. https://dx.doi.org/10.4314/ajsw.v13i3.2&#x0D; Visit journal website: https://ajsw.africasocialwork.net

Two-Cohort study on adoptive status non-disclosure in Lesotho: Implications for social work practice with African families

Two-Cohort study on adoptive status non-disclosure in Lesotho: Implications for social work practice with African families

Phase 2 study of bavituximab (bavi), a first-in-class antibody targeting phosphatidylserine (PS), plus pembrolizumab (P) in advanced gastric or gastroesophageal junction (GEJ) cancer.

e16023 Background: Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of PS through interaction with TIM/TAM receptor family members in the tumor microenvironment (TME), was evaluated in combination with P in patients with advanced gastric and GEJ cancer. Methods: ONCG100 was a phase 2, multicenter, open-label, two-cohort global study designed to assess the safety, tolerability, and antitumor activity of bavi (3 mg/kg, QW) plus P (200 mg, Q3W) in advanced gastric or GEJ cancer patients who progressed on ≥1 prior standard therapy (NCT04099641). Patients were checkpoint inhibitor (CPI) naive (Grp 1) or CPI relapsed (Grp 2); known MSI-H patients were excluded. RNA expression was analyzed in pre-treatment tumor tissue using the Xerna TME Panel, an RNA-based diagnostic, to prospectively test hypothesis that tumors with high immune or immune-suppressed TME subtypes (B+) are more likely to respond to bavi plus P than high angiogenic/immune-desert TME subtypes (B-). Results: A total of 80 patients enrolled (Grp 1 n=61, Grp 2 = 19). The most frequently reported Grade ≥ 3 treatment emergent adverse events (occurring in ≥10% of patients overall) were anaemia and gastric cancer progression (n= 10/AE). Key efficacy parameters for Grp 1 patients (2L 57.4%) are summarized in Table 1. In Grp 2, the ORR was 5.3% (95% CI: 0.1, 26.0), whereby 0 patients achieved a complete response and only 1 (5.3%) patient achieved a partial response as the best overall response (BOR). In the remaining patients, BOR was stable disease in 9 (47.4%) patients, progressive disease in 8 (42.1%) patients, and not evaluable in 1 (5.3%) patient. Conclusions: The combination of Bavi and P was well tolerated; observed AEs were consistent with known profiles for each agent. Higher ORRs were observed in CPI-naïve patients with B+ status and baseline NLR&lt;4, and of note, in patients with PD-L1 CPS &lt;1. Future studies may be planned to confirm the activity of Bavi in combination with P with patient selection based on a particular genetic signature. Clinical trial information: NCT04099641 . [Table: see text]