Survival After Sublobar Resection versus Lobectomy for Clinical Stage IA Lung Cancer An Analysis from the National Cancer Data Base

BackgroundRecent data have suggested possible oncologic equivalence of sublobar resection with lobectomy for early-stage non–smallcell lung cancer (NSCLC). Our aim was to evaluate and compare short-term and long-term survival for these surgical approaches.MethodsThis retrospective cohort study utilized the National Cancer Data Base. Patients undergoing lobectomy, segmentectomy, or wedge resection for preoperative clinical T1A N0 NSCLC from 2003 to 2011 were identified. Overall survival (OS) and 30-day mortality were analyzed using multivariable Cox proportional hazards models, logistic regression models, and propensity score matching. Further analysis of survival stratified by tumor size, facility type, number of lymph nodes (LNs) examined, and surgical margins was performed.ResultsA total of 13,606 patients were identified. After propensity score matching, 987 patients remained in each group. Both segmentectomy and wedge resection were associated with significantly worse OS when compared with lobectomy (hazard ratio: 1.70 and 1.45, respectively, both p < 0.001), with no difference in 30-day mortality. Median OS for lobectomy, segmentectomy, and wedge resection were 100, 74, and 68 months, respectively (p < 0.001). Finally, sublobar resection was associated with increased likelihood of positive surgical margins, lower likelihood of having more than three LNs examined, and significantly lower rates of nodal upstaging.ConclusionIn this large national-level, clinically diverse sample of clinical T1A NSCLC patients, wedge and segmental resections were shown to have significantly worse OS compared with lobectomy. Further patients undergoing sublobar resection were more likely to have inadequate lymphadenectomy and positive margins. Ongoing prospective study taking into account LN upstaging and margin status is still needed

Promoting positive development among refugee adolescents

Of the estimated 35.3 million refugees around the world (UNHCR, Figures at a Glance, 2022), approximately 50% are children under the age of 18. Refugee adolescents represent a unique group as they navigate developmental tasks in an unstable and often threatening environment or in resettlement contexts in which they often face marginalization. In addition to physiological, social, and psychological changes that mark adolescence, refugee youth often face traumatic experiences, acculturative stress, discrimination, and a lack of basic resources. In this consensus statement, we examine research on refugee adolescents' developmental tasks, acculturative tasks, and psychological adjustment using Suárez-Orozco and colleague's integrative risk and resilience model for immigrant-origin children and youth proposed by Suárez-Orozco et al. Finally, we discuss recommendations-moving from proximal to more distal contexts

Ultra-Processed Food Intake Is Associated with Non-Alcoholic Fatty Liver Disease in Adults: A Systematic Review and Meta-Analysis

Non-alcoholic fatty liver disease (NAFLD) is associated with overweight/obesity, metabolic syndrome and type 2 diabetes (T2D) due to chronic caloric excess and physical inactivity. Previous meta-analyses have confirmed associations between ultra-processed food (UPF) intake and obesity and T2D. We aim to ascertain the contribution of UPF consumption to the risk of developing NAFLD. We performed a systematic review and meta-analysis (PROSPERO (CRD42022368763)). All records registered on Ovid Medline and Web of Science were searched from inception until December 2022. Studies that assessed UPF consumption in adults, determined according to the NOVA food classification system, and that reported NAFLD determined by surrogate (steatosis) scores, imaging or liver biopsy were included. The association between UPF consumption and NAFLD was assessed using random-effects meta-analysis methods. Study quality was assessed, and evidence credibility evaluated, using the Newcastle Ottawa Scale and NutriGrade systems, respectively. A total of 5454 records were screened, and 112 records underwent full text review. From these, 9 studies (3 cross-sectional, 3 case-control and 3 cohort), analysing 60,961 individuals, were included in the current review. Both moderate (vs. low) (pooled relative risk 1.03 (1.00–1.07) (p = 0.04) (I2 = 0%)) and high (vs. low) (1.42 (1.16–1.75) (&lt;0.01) (I2 = 89%)) intake of UPF significantly increased the risk of NAFLD. Funnel plots demonstrate low risk of publication bias. Consumption of UPF is associated with NAFLD with a dose–response effect. Public health measures to reduce overconsumption of UPF are imperative to reduce the burden of NAFLD, and the related conditions, obesity and T2D.</jats:p

Ultra‐processed food and non‐communicable diseases in the United Kingdom: A narrative review and thematic synthesis of literature

SummaryThe social and economic constructs of the United Kingdom (UK) provide a fertile food environment for the dramatic expansion in the ultra‐processed food (UPF) market, driving increased UPF consumption. This has coincided with the significant increase in the incidence and prevalence of non‐communicable diseases (NCDs) such as obesity, type 2 diabetes, cardiovascular disease, and cancer, with an inherent impact on morbidity and mortality. Our review aims to assess the current epidemiological and public health trends in the United Kingdom, specifically examining consumption of UPFs and subsequent development of NCDs, summarizing existing meta‐analytical and experimental approaches. First, we address important socioeconomic and psychosocial domains that may contribute to increased availability and consumption of UPF. Additionally, we explore the putative mechanistic basis for the association between UPFs and NCDs: partly attributable to their energy density, the macro‐ and micronutrient composition (including high refined carbohydrate, saturated, and trans fats composition, in addition to low fiber and protein content), and artificially engineered additives and other compounds that adversely affect health in inadequately researched pathophysiological pathways. This review highlights the importance of promoting minimally processed diets to both clinical and political decision makers.</jats:p

Long‐term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma

Background: Gliomas are brain tumours arising from glial cells with an annual incidence of 4 to 11 people per 100,000. In this review we focus on gliomas with low aggressive potential in the short term, i.e. low‐grade gliomas. Most people with low‐grade gliomas are treated with surgery and may receive radiotherapy thereafter. However, there is concern about the possible long‐term effects of radiotherapy, especially on neurocognitive functioning. Objectives: To evaluate the long‐term neurocognitive and other side effects of radiotherapy (with or without chemotherapy) compared with no radiotherapy, or different types of radiotherapy, among people with glioma (where 'long‐term' is defined as at least two years after diagnosis); and to write a brief economic commentary. Search methods: We searched the following databases on 16 February 2018 and updated the search on 14 November 2018: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11) in the Cochrane Library; MEDLINE via Ovid; and Embase via Ovid. We also searched clinical trial registries and relevant conference proceedings from 2014 to 2018 to identify ongoing and unpublished studies. Selection criteria: Randomised and non‐randomised trials, and controlled before‐and‐after studies (CBAS). Participants were aged 16 years and older with cerebral glioma other than glioblastoma. We included studies where patients in at least one treatment arm received radiotherapy, with or without chemotherapy, and where neurocognitive outcomes were assessed two or more years after treatment. Data collection and analysis: Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of findings using the GRADE approach. Main results: The review includes nine studies: seven studies were of low‐grade glioma and two were of grade 3 glioma. Altogether 2406 participants were involved but there was high sample attrition and outcome data were available for a minority of people at final study assessments. In seven of the nine studies, participants were recruited to randomised controlled trials (RCTs) in which longer‐term follow‐up was undertaken in a subset of people that had survived without disease progression. There was moderate to high risk of bias in studies due to lack of blinding and high attrition, and in two observational studies there was high risk of selection bias. Paucity of data and risk of bias meant that evidence was of low to very low certainty. We were unable to combine results in meta‐analysis due to diversity in interventions and outcomes. The studies examined the following five comparisons. Radiotherapy versus no adjuvant treatment Two observational studies contributed data. At the 12‐year follow‐up in one study, the risk of cognitive impairment (defined as cognitive disability deficits in at least five of 18 neuropsychological tests) was greater in the radiotherapy group (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.02 to 3.71; n = 65); at five to six years the difference between groups did not reach statistical significance (RR 1.38, 95% CI 0.92 to 2.06; n = 195). In the other study, one subject in the radiotherapy group had cognitive impairment (defined as significant deterioration in eight of 12 neuropsychological tests) at two years compared with none in the control group (very low certainty evidence). With regard to neurocognitive scores, in one study the radiotherapy group was reported to have had significantly worse mean scores on some tests compared with no radiotherapy; however, the raw data were only given for significant findings. In the second study, there were no clear differences in any of the various cognitive outcomes at two years (n = 31) and four years (n = 15) (very low certainty evidence). Radiotherapy versus chemotherapy One RCT contributed data on cognitive impairment at up to three years with no clear difference between arms (RR 1.43, 95% CI 0.36 to 5.70, n = 117) (low‐certainty evidence). High‐dose radiotherapy versus low‐dose radiotherapy Only one of two studies reporting this comparison contributed data, and at two and five years there were no clear differences between high‐ and low‐dose radiotherapy arms (very low certainty evidence). Conventional radiotherapy versus stereotactic conformal radiotherapy One study involving younger people contributed limited data from the subgroup aged 16 to 25 years. The numbers of participants with neurocognitive impairment at five years after treatment were two out of 12 in the conventional arm versus none out of 11 in the stereotactic conformal radiotherapy arm (RR 4.62, 95% CI 0.25 to 86.72; n = 23; low‐certainty evidence). Chemoradiotherapy versus radiotherapy Two RCTs tested for cognitive impairment. One defined cognitive impairment as a decline of more than 3 points in MMSE score compared with baseline and reported data from 2‐year (110 participants), 3‐year (91 participants), and 5‐year (57 participants) follow‐up with no clear difference between the two arms at any time point. A second study did not report raw data but measured MMSE scores over five years in 126 participants at two years, 110 at three years, 69 at four years and 53 at five years. Authors concluded that there was no difference in MMSE scores between the two study arms (P = 0.4752) (low‐certainty evidence). Two RCTs reported quality of life (QoL) outcomes for this comparison. One reported no differences in Brain‐QoL scores between study arms over a 5‐year follow‐up period (P = 0.2767; no raw data were given and denominators were not stated). The other trial reported that the long‐term results of health‐related QoL showed no difference between the arms but did not give the raw data for overall HRQoL scores (low‐certainty evidence). We found no comparative data on endocrine dysfunction; we planned to develop a brief economic commentary but found no relevant economic studies for inclusion. Authors' conclusions: Radiotherapy for gliomas with a good prognosis may increase the risk of neurocognitive side effects in the long term; however the magnitude of the risk is uncertain. Evidence on long‐term neurocognitive side effects associated with chemoradiotherapy is also uncertain. Neurocognitive assessment should be an integral part of long‐term follow‐up in trials involving radiotherapy for lower‐grade gliomas to improve the certainty of evidence regarding long‐term neurocognitive effects. Such trials should also assess other potential long‐term effects, including endocrine dysfunction, and evaluate costs and cost effectiveness

Effects of gender-transformative relationships and sexuality education to reduce adolescent pregnancy (The JACK trial): a cluster randomised trial

BACKGROUND: The need to engage boys in gender-transformative relationships and sexuality education (RSE) to reduce adolescent pregnancy is endorsed by WHO. We aimed to test an intervention which used a gender-transformative approach to engage adolescents in RSE to prevent unprotected sex. METHODS: This cluster-randomised trial with process and economic evaluations tested a school-based intervention entitled If I Were Jack versus standard RSE (control) for students (aged 14-15 years) in UK schools. Schools were randomly allocated (1:1) and masked to allocation at baseline. The primary outcome was self-reported avoidance of unprotected sex (sexual abstinence or use of reliable contraception at last sex) after 12-14-months. We analysed the data using intention-to-treat mixed effects regression models. FINDINGS: Of 803 schools assessed for eligibility, 263 schools were invited by letter, of which 66 schools agreed to be randomly assigned, of which 62 schools completed follow-up. The trial was done between Feb 1, 2018, and March 6, 2020. 8216 students participated at baseline in 2018; 6561 (79·85%) provided 12-14 months follow-up. There was no significant difference in the primary outcome of avoidance of unprotected sex: 2648 (86·62) of 3057 in the intervention group avoided unprotected sex versus 2768 (86·41%) of 3203 in the control group (adjusted odds ratio [aOR] 0·85 [95% CI 0·58-1·26], p=0·42). Exploratory post-hoc analysis of the two components of the primary outcome showed that significantly more intervention students used reliable contraception at last sex compared with control students and there was no significant difference between the groups for sexual abstinence. No adverse events were reported. INTERPRETATION: The intervention had a null effect on the primary outcome of preventing unprotected sex (increasing sexual abstinence or use of reliable contraception) in the whole student population. However, the results showed significant increases in use of reliable contraceptives for sexually active students. Engaging all young people early through RSE is important so that as they become sexually active, rates of unprotected sex are reduced. FUNDING: National Institute for Health Research

Telomere length measurement by qPCR in birds is affected by storage method of blood samples

Given the potential role of telomeres as biomarkers of individual health and ageing, there is an increasing interest in studying telomere dynamics in a wider range of taxa in the fields of ecology and evolutionary biology. Measuring telomere length across the lifespan in wild animal systems is essential for testing these hypotheses, and may be aided by archived blood samples collected as part of longitudinal field studies. However, sample collection, storage, and DNA extraction methods may influence telomere length measurement, and it may, therefore, be difficult to balance consistency in sampling protocol with making the most of available samples. We used two complementary approaches to examine the impacts of sample storage method on measurements of relative telomere length (RTL) by qPCR, particularly focusing on FTA (Flinders Technology Associates) cards as a long-term storage solution. We used blood samples from wandering albatrosses collected over 14 years and stored in three different ways (n = 179), and also blood samples from captive zebra finches (n = 30) that were each stored using three different methods. Sample storage method influenced RTL in both studies, and samples on FTA cards had significantly shorter RTL measurements. There was no significant correlation between RTL measured in zebra finch blood on FTA cards and the same samples stored either as frozen whole blood or as extracted DNA. These results highlight the importance of consistency of sampling protocol, particularly in the context of long-term field studies, and suggest that FTA cards should not be used as a long-term storage solution to measure RTL without validation

School-based relationship and sexuality education intervention engaging adolescent boys for the reductions of teenage pregnancy: the JACK cluster RCT

BACKGROUND: The need to engage boys in gender-transformative relationships and sexuality education (RSE) to reduce adolescent pregnancy is endorsed by the World Health Organization and the United Nations Educational, Scientific and Cultural Organization. OBJECTIVES: To evaluate the effects of If I Were Jack on the avoidance of unprotected sex and other sexual health outcomes. DESIGN: A cluster randomised trial, incorporating health economics and process evaluations. SETTING: Sixty-six schools across the four nations of the UK. PARTICIPANTS: Students aged 13-14 years. INTERVENTION: A school-based, teacher-delivered, gender-transformative RSE intervention (If I Were Jack) versus standard RSE. MAIN OUTCOME MEASURES: Self-reported avoidance of unprotected sex (sexual abstinence or reliable contraceptive use at last sex) after 12-14 months. Secondary outcomes included knowledge, attitudes, skills, intentions and sexual behaviours. RESULTS: The analysis population comprised 6556 students: 86.6% of students in the intervention group avoided unprotected sex, compared with 86.4% in the control group {adjusted odds ratio 0.85 [95% confidence interval (CI) 0.58 to 1.26], p = 0.42}. An exploratory post hoc analysis showed no difference for sexual abstinence [78.30% intervention group vs. 78.25% control group; adjusted odds ratio 0.85 (95% CI 0.58 to 1.24), p = 0.39], but more intervention group students than control group students used reliable contraception at last sex [39.62% vs. 26.36%; adjusted odds ratio 0.52 (95% CI 0.29 to 0.920), p = 0.025]. Students in schools allocated to receive the intervention had significantly higher scores on knowledge [adjusted mean difference 0.18 (95% CI 0.024 to 0.34), p = 0.02], gender-equitable attitudes and intentions to avoid unintended pregnancy [adjusted mean difference 0.61 (95% CI 0.16 to 1.07), p = 0.01] than students in schools allocated to receive the control. There were positive but non-significant differences in sexual self-efficacy and communication skills. The total mean incremental cost of the intervention compared with standard RSE was £2.83 (95% CI -£2.64 to £8.29) per student. Over a 20-year time horizon, the intervention is likely to be cost-effective owing to its impact on unprotected sex because it would result in 379 (95% CI 231 to 477) fewer unintended pregnancies, 680 (95% CI 189 to 1467) fewer sexually transmitted infections and a gain of 10 (95% CI 5 to 16) quality-adjusted life-years per 100,000 students for a cost saving of £9.89 (95% CI -£15.60 to -£3.83). LIMITATIONS: The trial is underpowered to detect some effects because four schools withdrew and the intraclass correlation coefficient (0.12) was larger than that in sample size calculation (0.01). CONCLUSIONS: We present, to our knowledge, the first evidence from a randomised trial that a school-based, male engagement gender-transformative RSE intervention, although not effective in increasing avoidance of unprotected sex (defined as sexual abstinence or use of reliable contraception at last sex) among all students, did increase the use of reliable contraception at last sex among students who were, or became, sexually active by 12-14 months after the intervention. The trial demonstrated that engaging all adolescents early through RSE is important so that, as they become sexually active, rates of unprotected sex are reduced, and that doing so is likely to be cost-effective. FUTURE WORK: Future studies should consider the longer-term effects of gender-transformative RSE as students become sexually active. Gender-transformative RSE could be adapted to address broader sexual health and other settings. TRIAL REGISTRATION: This trial is registered as ISRCTN10751359. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (PHR 15/181/01) and will be published in full in Public Health Research; Vol. 11, No. 8. See the NIHR Journals Library website for further project information

Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery

Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and threematernally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins.We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such asmRNAexport, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in human

Proton vs. Photon Radiation Therapy for Primary Gliomas: An Analysis of the National Cancer Data Base

Background: To investigate the impact of proton radiotherapy (PBT) on overall survival (OS) and evaluate PBT usage trends for patients with gliomas in the National Cancer Data Base (NCDB).Methods: Patients with a diagnosis of World Health Organization (WHO) Grade I-IV glioma treated with definitive radiation therapy (RT) between the years of 2004–13 were identified. Patients were stratified based on WHO Grade and photon radiotherapy (XRT) vs. PBT. Univariate (UVA) and multivariable analysis (MVA) with OS were performed by Cox proportional hazards model and log-rank tests. Propensity score (PS) weighting was utilized to account for differences in patient characteristics and to minimize selection bias.Results: There were a total of 49,405 patients treated with XRT and 170 patients treated with PBT. Median follow-up time was 62.1 months. On MVA, the following factors were associated with receipt of PBT (all p &lt; 0.05): WHO Grade I-II gliomas, treatment at an academic/research program, west geographic facility location, and surgical resection. After PS weighting, all patients treated with PBT were found to have superior median and 5 year survival than patients treated with XRT: 45.9 vs. 29.7 months (p = 0.009) and 46.1 vs. 35.5% (p = 0.0160), respectively.Conclusions: PBT is associated with improved OS compared to XRT for patients with gliomas. This finding warrants verification in the randomized trial setting in order to account for potential patient imbalances not adequately captured by the NCDB, such as tumor molecular characteristics and patient performance status.Importance of the Study: This is the first study that compares the outcomes of patients treated with photon based radiotherapy vs. proton based radiotherapy for patients with gliomas. In this retrospective analysis, the results demonstrate that proton therapy is associated with improved outcomes which support ongoing prospective, randomized clinical trials comparing the two modalities in patients with gliomas