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Cohort profile: the United Kingdom Childhood Cancer Study (UKCCS) - a UK-wide population-based study examining the health of cancer survivors

Por: Roman · E. · Kane · E. · Smith · A. · Howell · D. · Sheridan · R. · Simpson · J. · Bonaventure · A. · Kinsey · S.
Purpose

The United Kingdom Childhood Cancer Study’s (UKCCS’s) matched cohort was established to examine the longer term morbidity and mortality of individuals previously diagnosed with cancer before 15 years of age, comparing future healthcare patterns in 5-year cancer survivors to baseline activity seen in age- and sex-matched individuals from the general population.

Participants

Predicated on a national childhood cancer case-control study conducted in the early 1990s (4430 cases, 9753 controls) in England, Scotland and Wales, the case population comprises 3125 cancer survivors (>5 years), and the control population 7156 age- and sex-matched individuals from the general population who did not have cancer as a child. Participants are now being followed up via linkage to national administrative healthcare databases (deaths, cancers and secondary care hospital activity).

Findings to date

Enabling the creation of cohorts with minimal selection bias and loss to follow-up, the original case-control study registered all newly diagnosed cases of childhood cancer and their corresponding controls, regardless of their family’s participation. Early findings based on the registered case population found marked survival variations with age and sex across subtypes and differences with deprivation among acute lymphoblastic leukaemia (ALL) survivors. More recently, comparing the health-activity patterns of the case and control populations revealed that survivors of childhood ALL experienced excess outpatient and inpatient activity across their teenage/young adult years. Adding to increased risks of cancer and death and involving most clinical specialties, excesses were not related to routine follow-up monitoring and showed no signs of diminishing over time.

Future plans

With annual linkage updates, the UKCCS’s maturing population-based matched cohorts provide the foundation for tracking the health of individuals through their lifetime. Comparing the experience of childhood cancer survivors to that of unaffected general-population counterparts, this will include examining subsequent morbidity and mortality, secondary care hospital activity and the impact of deprivation on longer term outcomes.

In silico exploration of <i>Serratia</i> sp. BRL41 genome for detecting prodigiosin Biosynthetic Gene Cluster (BGC) and in vitro antimicrobial activity assessment of secreted prodigiosin

by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.

Molecular characterization of <i>G6PD</i> mutations identifies new mutations and a high frequency of intronic variants in Thai females

by Kamonwan Chamchoy, Sirapapha Sudsumrit, Jutamas Wongwigkan, Songsak Petmitr, Duantida Songdej, Emily R. Adams, Thomas Edwards, Ubolsree Leartsakulpanich, Usa Boonyuen

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy caused by mutations in the G6PD gene. A medical concern associated with G6PD deficiency is acute hemolytic anemia induced by certain foods, drugs, and infections. Although phenotypic tests can correctly identify hemizygous males, as well as homozygous and compound heterozygous females, heterozygous females with a wide range of G6PD activity may be misclassified as normal. This study aimed to develop multiplex high-resolution melting (HRM) analyses to enable the accurate detection of G6PD mutations, especially among females with heterozygous deficiency. Multiplex HRM assays were developed to detect six G6PD variants, i.e., G6PD Gaohe (c.95A>G), G6PD Chinese-4 (c.392G>T), G6PD Mahidol (c.487G>A), G6PD Viangchan (c.871G>A), G6PD Chinese-5 (c.1024C>T), and G6PD Union (c.1360C>T) in two reactions. The assays were validated and then applied to genotype G6PD mutations in 248 Thai females. The sensitivity of the HRM assays developed was 100% [95% confidence interval (CI): 94.40%–100%] with a specificity of 100% (95% CI: 88.78%–100%) for detecting these six mutations. The prevalence of G6PD deficiency was estimated as 3.63% (9/248) for G6PD deficiency and 31.05% (77/248) for intermediate deficiency by phenotypic assay. The developed HRM assays identified three participants with normal enzyme activity as heterozygous for G6PD Viangchan. Interestingly, a deletion in intron 5 nucleotide position 637/638 (c.486-34delT) was also detected by the developed HRM assays. G6PD genotyping revealed a total of 12 G6PD genotypes, with a high prevalence of intronic variants. Our results suggested that HRM analysis-based genotyping is a simple and reliable approach for detecting G6PD mutations, and could be used to prevent the misdiagnosis of heterozygous females by phenotypic assay. This study also sheds light on the possibility of overlooking intronic variants, which could affect G6PD expression and contribute to enzyme deficiency.

Effects of a laboratory-based aerobic exercise intervention on brain volume and cardiovascular health markers: protocol for a randomised clinical trial

Por: Molina Hidalgo · C. · Collins · A. M. · Crisafio · M. E. · Grove · G. · Kamarck · T. W. · Kang · C. · Leckie · R. L. · MacDonald · M. · Manuck · S. B. · Marsland · A. L. · Muldoon · M. F. · Rasero · J. · Scudder · M. R. · Velazquez-Diaz · D. · Verstynen · T. · Wan · L. · Gianaros · P. J
Introduction

Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk.

Methods and analysis

In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain–body interactions in the context of cardiovascular health.

Ethics and dissemination

Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.

Trial registration number

NCT03841669.

Salmonella Vaccine Study in Oxford (SALVO) trial: protocol for an observer-participant blind randomised placebo-controlled trial of the iNTS-GMMA vaccine within a European cohort

Por: Hanumunthadu · B. · Kanji · N. · Owino · N. · Ferreira Da Silva · C. · Robinson · H. · White · R. · Ferruzzi · P. · Nakakana · U. · Canals · R. · Pollard · A. J. · Ramasamy · M. · Vacc-iNTS Consortium · Agyapong · Breghi · Crump · Fiorino · Gordon · Jacobs · Kariuki · Malvolti · Mante
Introduction

Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.

Method and analysis

The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.

The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.

Ethics and dissemination

Ethical approval for this study has been obtained from the South Central—Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.

Trial registration number

EudraCT Number: 2020-000510-14.

Gender disparities, causes and predictors of immediate and short-term cardiovascular readmissions following COVID-19-related hospitalisations in the USA

Por: Vardar · U. · Shaka · H. · Kumi · D. · Gajjar · R. · Bess · O. · Kanemo · P. · Shaka · A. · Baskaran · N.
Objectives

In this study, we aimed to identify the causes, predictors and gender disparities of 30-day and 90-day cardiovascular readmissions after COVID-19-related hospitalisations using National Readmission Database (NRD) 2020.

Setting

We used the NRD from 2020 to identify hospitalised adults with a principal diagnosis of COVID-19 infection.

Participants

We included subjects who were readmitted within 30 days and 90 days after index admission. We excluded subjects with elective and traumatic admissions. We used a multivariate Cox regression model to identify independent predictors of readmission.

Primary and secondary outcomes measures

Our outcomes were inpatient mortality, 30-day and 90-day cardiovascular readmission rates following COVID-19 infection.

Results

During the study period, there were 1 024 492 index hospitalisations with a primary diagnosis of COVID-19 infection in the 2020 NRD database, 644 903 (62.9%) were included for 30-day readmission analysis, and 418 122 (40.8%) were included for 90-day readmission analysis. Of patients involved in the 30-day analysis, 7140 (1.1%) patients had a readmission within 30 days; of patients involved in the 90-day analysis, 8379 (2.0%) had a readmission within 90 days due to primarily cardiovascular causes. Cox regression analysis revealed that the female sex (aHR 0.89; 95% CI 0.82 to 0.95; p=0.001) was associated with a lower hazard of 30-day cardiovascular readmissions; however, congestive heart failure (aHR 2.45; 95% CI 2.2 to 2.72; p

Conclusion

Our study demonstrates that male gender, heart failure, arrhythmias and valvular disease carry higher hazards of 30-day and 90-day cardiovascular readmissions. Identifying risk factors and common causes of readmission may assist with lowering the burden of cardiovascular disease in patients with COVID-19 infection.

Randomized clinical trial to compare the efficacy of self-expanding bare metal nitinol stent and balloon angioplasty alone for below-the-knee lesions following successful balloon angioplasty: 1-year clinical outcomes

by Jihun Ahn, HyeYon Yu, Seung-Woon Rha, Byoung Geol Choi, Dong Oh Kang, Cheol Ung Choi, Sangho Park, Jon Seo, Kichang Kim, Minung Kim, Yong Hoon Kim, Yong Seong Seo

This prospective, multicenter, randomized study aimed to compare the 1-year clinical outcomes after primary stenting with self-expanding bare metal nitinol stent (SENS) and plain old balloon angioplasty (POBA) in patients with critical limb ischemia (CLI) and below-the-knee (BTK) lesions. Overall, 119 patients with CLI and BTK lesions were randomized to POBA alone (POBA group, 61 patients) or primary stenting with SENS (stenting group, 58 patients) after achieving acceptable POBA results in target BTK lesions. Clinical outcomes including amputation and revascularization rates were prospectively compared for 1 year. After 1 year, similar incidence rates of individual clinical endpoints, including cardiac death (6.5% vs. 5.1%, p > 0.999), myocardial infarction (1.6% vs. 0.0%, p > 0.999), repeat revascularization (19.6% vs. 18.9%, p = 0.922), target lesion revascularization (13.1% vs. 17.2%, p = 0.530), and amputation (4.9% vs. 0.0%, p = 0.244), were observed. POBA appeared to have acceptable treatment outcomes compared with primary stenting with SENS after 1 year in CLI patients with BTK lesions undergoing percutaneous transluminal angioplasty (PTA).

Oral health in patients with different sites of head and neck squamous cell carcinoma is not different

by Philipp Kanzow, Katharina Mielke, Franziska Haupt, Susanne Wiegand, Henning Schliephake, Dirk Beutner, Annette Wiegand

Oral health might not only act as risk factor for head and neck squamous cell carcinoma (HNSCC), but might also have a predictive value for the patients’ survival. Currently, information on the effect of oral health on survival of patients with different sites of HNSCC is lacking. This single-center retrospective study aimed to compare oral health in patients with different sites of HNSCC and to analyse whether oral health is associated with survival in the different subsets of HNSCC patients. Dental records of HNSCC patients referred for dental assessment prior to radio(chemo)therapy were included. Patient-related parameters (age at time of diagnosis, sex, tobacco exposure, alcohol consumption, HPV status), treatment data (primary treatment, intent), performance status, tumor demographics (anatomical site, TNM staging), and oral health parameters (DMFT, periodontal health, teeth with/without root canal treatment and with/without periodontitis apicalis) were obtained. Oral health parameters were compared between different anatomical sites. Survival of all HNSCC patients and of individual subsets was assessed using Kaplan-Meier statistics, and the effect of tumor demographics, patient-related parameters, and oral health on survival was analysed by cox regression analyses (α = 5%). 371 patients with HNSCC (oral: n = 86, oropharyngeal: n = 174, hypopharyngeal: n = 59, laryngeal: n = 15, other: n = 37) were included. Oral health parameters did not differ between subsets (padj.≥0.199). Five-year cumulative survival of HNSCC patients amounted to 78.6%. Only for HNSCC originating in the oral cavity and oropharynx, survival was associated with the treatment intent (p = 0.015) or performance status (p = 0.007) in the multivariable analyses, respectively. Within the limitations of this study, oral health was not different between different subsets and had no significant effect on survival of HNSCC patients.

The effect of bed exercises following major abdominal surgery on early ambulation, mobilization, pain and anxiety: A randomized‐controlled trial

Abstract

This randomized-controlled trial aimed to investigate the effect of bed exercises on postoperative anxiety, pain, early ambulation and mobilization. This study was conducted with a randomized-controlled trial design and in the general surgical clinic of a research and training hospital. A total of 120 patients (60 in the experimental group and 60 in the control group) scheduled for major abdominal surgery took part in the study. The data were collected using a patient information form, the Anxiety Specific to Surgery Questionnaire and the Visual Analog Scale through face-to-face interviews. The patients in the experimental group performed 15-min bed exercises on the day of their operation, as well as on the postoperative first and second days, and the control group underwent only the routinely performed procedures in the clinic. The data were analysed using descriptive statistics, analysis of variance and t-tests. The sample of our study included major abdominal surgery patients. Ambulation was achieved at a mean time of 4 h earlier in the experimental group. On the postoperative first and second days, the patients in the experimental group had mean mobilization durations that were approximately 2 h longer compared with the patients in the control group. Moreover, the postoperative pain and anxiety levels of the patients in the experimental group were significantly lower than those of the patients in the control group (p < 0.05). We recommend that bed exercises be performed to lower anxiety and pain severity, achieve early ambulation and increase the duration of mobilization among patients following major abdominal surgery.

The incidence of intraoperatively acquired pressure injuries in the park‐bench position was reduced by applying soft silicone multilayer foam dressings

Abstract

The Park-Bench Position (PBP) is associated with a high incidence rate of intraoperatively acquired pressure injuries (IAPIs). Preventive measures must be established to prevent the development of IAPIs. We investigated the risk factors for PBP by applying a soft silicone multilayered foam dressing (SMD) under core temperature management to prevent IAPIs. We conducted a prospective, single-centre, open-label observational study of patients undergoing elective neurosurgery operations using PBP in a university hospital in Japan. The incidence rate of IAPIs in this study was compared with that in our two previous studies, in which a film dressing was applied and core temperature management was not performed. IAPIs developed in 90 patients (6.7%); in the lateral thoracic region in five patients and the iliac crest region in one patient. The operative time (every 1 h: p = 0.0001, OR: odds ratio 3.62, 95% CI: confidence interval 1.73–11.42) was significantly associated with the incidence of IAPIs. In our two previous studies, the incidence rate of IAPIs was 11.0% and 24.1%, respectively, when film dressing was used. SMD may weaken the involvement of risk factors in IAPIs.

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