Recent Contributions of Proteomics to Our Understanding of Reversible Nε-Lysine Acylation in Bacteria.

Post-translational modifications (PTMs) have been extensively studied in both eukaryotes and prokaryotes. Lysine acetylation, originally thought to be a rare occurrence in bacteria, is now recognized as a prevalent and important PTM in more than 50 species. This expansion in interest in bacterial PTMs became possible with the advancement of mass spectrometry technology and improved reagents such as acyl-modification specific antibodies. In this Review, we discuss how mass spectrometry-based proteomic studies of lysine acetylation and other acyl modifications have contributed to our understanding of bacterial physiology, focusing on recently published studies from 2018 to 2023. We begin with a discussion of approaches used to study bacterial PTMs. Next, we discuss newly characterized acylomes, including acetylomes, succinylomes, and malonylomes, in different bacterial species. In addition, we examine proteomic contributions to our understanding of bacterial virulence and biofilm formation. Finally, we discuss the contributions of mass spectrometry to our understanding of the mechanisms of acetylation, both enzymatic and nonenzymatic. We end with a discussion of the current state of the field and possible future research avenues to explore.

Myocarditis Following COVID-19 Vaccination: A Systematic Review of Case Reports.

Introduction: COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often presents with a spectrum of symptoms at varying levels of severity, ranging from asymptomatic patients to those with fatal complications, such as myocarditis. With increased availability of COVID-19 vaccines, the awareness of possible side effects has expanded as reports surface. This study reviewed cases of myocarditis following COVID-19 vaccination and with existing literature on COVID-19 infection-induced myocarditis to compare clinical courses and analyze possible mechanisms of action. Methods: A systematic review of literature was conducted to identify published case reports (as of February 3, 2022) pertaining to the development of myocarditis following COVID-19 vaccination with either Pfizer or Moderna for an in-depth analysis. Additional subgroup analyses were conducted based on age, past medical history, vaccine manufacturer, and dose number. Results: There were 53 eligible case reports that were included in this study. Patients were mostly male with a median age of 24 years, and the most reported symptom upon presentation was chest pain. Seventy percent of the cases involved the Pfizer vaccine with a majority of myocarditis developing subsequent to second dose. Resolution of symptoms was achieved in all but one patient. Clinical severity, as measured primarily by left ventricular ejection fraction, appeared to be worse among adult patients than pediatric, as well as for patients with comorbidities. Conclusion: This study revealed an observable association between COVID-19 vaccines and myocarditis. However, the clinical course and prognosis seem favorable and less prevalent than those conferred from natural infection.

Attention-Deficit/Hyperactivity Disorder as a Potential Risk Factor for Dementia and Other Neurocognitive Disorders: A Systematic Review.

Background: Attention-deficit/hyperactivity disorder (ADHD), a common neurodevelopmental condition now recognized to persist into older adulthood, has been postulated to be a risk factor for neurocognitive disorders given the overlap in clinical features and neurobiology, as well as the complex interplay between ADHD and known risk factors for dementia. Studies have emerged assessing this relationship, but there has not yet been a comprehensive systematic review addressing this topic. Objective: To assess whether ADHD is a risk factor for neurocognitive disorders and to explore possible mechanisms for such an association. Methods: A systematic review of the literature was conducted using Medline, Embase, and PsycINFO from inception until June 4, 2023. Studies were included if they assessed whether or how ADHD may be a risk factor for neurocognitive disorders. Studies were excluded if they were not primary literature, not published in a peer-reviewed journal, not in English, and/or used non-human subjects. Study quality was assessed using the QualSyst tool. Results: Sixteen studies met inclusion criteria. Seven studies found a positive association between ADHD and neurocognitive disorders (all-cause dementia in four studies, Alzheimer's disease in three studies, Lewy body dementia in two studies, and mild cognitive impairment in one study). Four studies did not find an association. Five studies pertained to possible mechanisms for an association, including genetics, with minimal significant findings. Conclusions: ADHD may be a risk factor for certain neurocognitive disorders, although the evidence base is limited, and the absolute risk is small. Possible explanations include genetic and lifestyle factors.

Legacy lessons from the COVID-19 era to improve trial participation and retention: Views from trial participants, PPIE contributors and trial staff across the NIHR portfolio.

BACKGROUND: The Covid-19 pandemic had a profound effect on the delivery of healthcare research. Covid-19 research was prioritised and many non-essential trials were paused. This study explores the engagement experiences of trial participants', PPIE contributors' and trial staff during the Covid-19 pandemic and towards recovery and restoring a diverse and balanced UK clinical trials portfolio. METHODS: Interviews and focus groups were undertaken with PPIE contributors, trial participants and trial staff members from NIHR research trials across the UK (November 2020-June 2021) across portfolio specialities: Cancer, Oral and Dental Health, Musculoskeletal Disorders, Cardiovascular Disease, Neurological Disorders, Primary Care, and Conditions associated with susceptibility to Covid-19 (Diabetes, Stroke, Respiratory Disorders). Topic guides were developed for each participant group and interviews were conducted over Zoom. The transcripts were analysed using codebook thematic analysis in NVivo (V.12). RESULTS: 106 participants comprising, 45 PPIE contributors, 27 trial participants and 34 trial staff members were recruited. Three themes to engagement with trials during Covid-19 were developed. 1) Ensuring continued contact. Continued and tailored communication, having a trial point of contact and regular updates all enhanced trial engagement and retention. Patients' unfamiliarity with materials being sent electronically reduced engagement and trust. 2) A balanced move to remote consultations. Remote follow-up and monitoring were convenient and allowed for wider recruitment across the UK. Participants were more likely to discuss personal subjects in their own homes. Remote visits lacked a personal touch, some concerns over missed diagnoses or being unable to appreciate the situation, technical abilities or equipment failures were seen as barriers, especially for disadvantaged or older people. 3) The importance of feeling fully informed. Factors that supported attendance were knowledge about trial conduct adherence to Covid-19 regulations, social distancing, clear signage at the site and opportunities to ask questions. Barriers included not knowing what to expect and not feeling safe with rules and regulations. CONCLUSIONS: Our findings highlight a number of ways to future proof trial delivery against future pandemics or disruptions such as offering online options to participate in research, ensuring consistent communication between participants and the research team, making sure participants feel fully informed and the continued reassurance of safety in the clinical setting.

Online video resources pertaining to cerebral palsy: A YouTube-based quality control study.

Aim: To assess the content and quality of YouTube videos related to cerebral palsy to provide insights into the online video resources available for individuals affected by cerebral palsy and suggest strategies for improvement. Methods: YouTube videos were analyzed based on interaction parameters, content characteristics/category, and video source. Video reliability and quality were assessed using the Journal of American Medical Association benchmark, Global Quality Scale, and cerebral palsy-specific score. Statistical analyses examined associations between video characteristics and reliability/quality scores. Results: The average video (n = 48) length was 6.8 min, with 29 informational and 19 experiential videos. The mean Journal of American Medical Association score was 2.0, indicating moderate reliability. The Global Quality Scale suggested good quality content (average: 3.5), but only 14% were rated as good via cerebral palsy-specific score. Higher views were associated with higher Journal of American Medical Association score and cerebral palsy-specific score (p = 0.002 and p = 0.006), and nonphysician medical expert videos had lower Journal of American Medical Association scores than academic videos (p = 0.042). Video content was not significantly associated with either score. Conclusion: YouTube provides moderate to good quality information on cerebral palsy. Critical evaluation of video sources and content is essential. Findings can guide strategies to enhance the quality of cerebral palsy-related YouTube content, benefiting individuals with cerebral palsy, health care providers, and caregivers.

Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates.

Infections due to drug-resistant Acinetobacter baumannii strains are increasing and cause significant morbidity and mortality, especially in hospitalized and critically ill patients. A. baumannii rapidly develops resistance to numerous antibiotics, and antibiotics traditionally used against this deadly pathogen have been failing in recent years, highlighting the need to identify new treatment strategies. Treatment options that have shown promise include revisiting common antibiotics not typically used against A. baumannii, evaluating new antibiotics recently introduced to market, and identifying combinations of antibiotics that display synergistic interactions. In this study, we characterized the antibiotic susceptibility profiles of extensively (XDR) and pandrug-resistant (PDR) A. baumannii patient isolates. We examined the potency of 22 standard-of-care antibiotics and the newer antibiotics eravacycline, omadacycline, and plazomicin against these strains. Furthermore, we examined combinations of these antibiotics against our collection to identify synergistic effects. We found that this collection is highly resistant to most or all standard-of-care antibiotics, except for minocycline and rifampin. We show that eravacycline and omadacycline are effective against these strains based on minimum inhibitory concentrations. We also identified two highly effective combinations, cefepime and amikacin and cefepime and ampicillin-sulbactam, which exhibited high rates of synergy against this collection. This information is valuable in our battle against highly drug resistant and virtually untreatable A. baumannii infections.

Nε-lysine acetylation of the histone-like protein HBsu influences antibiotic survival and persistence in Bacillus subtilis.

Nε-lysine acetylation is recognized as a prevalent post-translational modification (PTM) that regulates proteins across all three domains of life. In Bacillus subtilis, the histone-like protein HBsu is acetylated at seven sites, which regulates DNA compaction and the process of sporulation. In Mycobacteria, DNA compaction is a survival strategy in response antibiotic exposure. Acetylation of the HBsu ortholog HupB decondenses the chromosome to escape this drug-induced, non-growing state, and in addition, regulates the formation of drug-tolerant subpopulations by altering gene expression. We hypothesized that the acetylation of HBsu plays similar regulatory roles. First, we measured nucleoid area by fluorescence microscopy and in agreement, we found that wild-type cells compacted their nucleoids upon kanamycin exposure, but not exposure to tetracycline. We analyzed a collection of HBsu mutants that contain lysine substitutions that mimic the acetylated (glutamine) or unacetylated (arginine) forms of the protein. Our findings indicate that some level of acetylation is required at K3 for a proper response and K75 must be deacetylated. Next, we performed time-kill assays of wild-type and mutant strains in the presence of different antibiotics and found that interfering with HBsu acetylation led to faster killing rates. Finally, we examined the persistent subpopulation and found that altering the acetylation status of HBsu led to an increase in persister cell formation. In addition, we found that most of the deacetylation-mimic mutants, which have compacted nucleoids, were delayed in resuming growth following removal of the antibiotic, suggesting that acetylation is required to escape the persistent state. Together, this data adds an additional regulatory role for HBsu acetylation and further supports the existence of a histone-like code in bacteria.

Changes in fatigue over 2 years are associated with activity of inflammatory bowel disease and psychological factors.

BACKGROUND & AIMS: Cross-sectional studies have identified high levels of fatigue in patients with active or quiescent inflammatory bowel disease (IBD), but there has been little attention to the long-term effects of fatigue in these patients. We performed a longitudinal study of fatigue in patients with IBD to determine its course and contributing factors. METHODS: Data were obtained from participants in the Manitoba IBD Cohort Study (N = 312; 51% with Crohn's disease), a longitudinal population-based study. Symptomatic disease activity was measured every 6 months for 2 years to characterize long-term disease patterns as active, fluctuating, or inactive, based on the validated Manitoba IBD Index. We collected data concurrently on fatigue (Multidimensional Fatigue Inventory), psychological function, and laboratory biomarkers at the point of study entry and 1 and 2 years later. RESULTS: Of the study participants, 26% had consistently inactive, 29% had fluctuating, and 45% had consistently active disease over the 2-year time period. Mean levels of fatigue were strongly associated with disease activity; participants with consistently inactive disease had the lowest level of fatigue at each time point. Multivariate analyses indicated fatigue levels increased over time regardless of disease pattern (P < .001). Adjusting for disease activity, disease type and age, sex (female; P < .001), and psychological variables of distress (P < .001), reduced psychological well-being (P = .002) and poor sleep quality (P < .001) were associated independently with increases in fatigue over time. CONCLUSIONS: Fatigue can increase over time in patients with IBD, even when their disease is in remission. Psychological factors are useful targets for intervention to reduce fatigue.

Is iron deficiency in the absence of anemia associated with fatigue in inflammatory bowel disease?

OBJECTIVES: We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflammatory bowel disease (IBD). METHODS: We assessed iron deficiency and anemia in 280 participants from the population-based Manitoba IBD Cohort Study. RESULTS: Iron deficiency was identified in 20% with Crohn's disease and 27% with ulcerative colitis. Anemia was identified overall in 50 (18%), with 230 who were nonanemic. In the nonanemic subgroup, there were no significant differences between iron-deficient and -sufficient groups in mean fatigue levels or proportions with problematic fatigue. There was no unique contribution of iron deficiency to problematic fatigue after adjustment for active disease and anemia. CONCLUSIONS: There was no evidence of an association between iron deficiency and fatigue in the absence of anemia, suggesting that iron deficiency is not a clinically relevant contributor to fatigue in IBD.

Relative importance measures for reprioritization response shift.

PURPOSE: Response shift (RS), a change in the meaning of an individual's self-evaluation of a target construct, such as health-related quality of life (HRQOL), can affect the interpretation of change in measures of the construct collected over time. This study proposes new statistical methods to test for reprioritization RS, in which the relative importance of HRQOL domains changes over time. METHODS: The methods use descriptive discriminant analysis or logistic regression models and bootstrap inference to test for change in relative importance weights (method 1) or ranks (method 2) for discriminating between patient groups at two occasions. The methods are demonstrated using data from the Manitoba Inflammatory Bowel Disease (IBD) Cohort Study (n = 388). Reprioritization of domains from the IBD Questionnaire (IBDQ) and SF-36 was investigated for groups with active and inactive disease symptoms. RESULTS: The IBDQ bowel symptoms and SF-36 bodily pain domains had the highest ranks for group discrimination. Using Method 1, there was evidence of reprioritization RS in the IBDQ social functioning domain and the SF-36 bodily pain and social functioning domains. Method 2 did not detect change for any of the domains. CONCLUSIONS: Compared to IBD patients without active disease symptoms, those with active symptoms were likely to change the meaning of their self-evaluations of pain and social interactions. Further research is needed to compare these new RS detection methods under a variety of data analytic conditions before recommendations about the optimal method can be made.

Lanthanide complexes as chiral probes exploiting circularly polarized luminescence.

Optical probes that provide information about local chirality have been developed based on changes to the circular polarisation of emitted light. Highly emissive complexes of lanthanide ions are ideally suited for CPL spectroscopy and the design criteria for developing such probes are defined, based on a rigorous stereochemical analysis. The perturbation of a dynamically racemic complex may occur either by a change in complex constitution or by non-covalent association. With complexes of enantiopure ligands, perturbation may involve either dynamic helicity inversion or a reversible change in the lanthanide coordination environment.

The Manitoba Inflammatory Bowel Disease Cohort Study: a prospective longitudinal evaluation of the use of complementary and alternative medicine services and products.

OBJECTIVE: To determine the prevalence of complementary and alternative medicine (CAM) use over time in a population-based cohort of patients with inflammatory bowel disease (IBD). METHODS: The Manitoba IBD Cohort Study is a longitudinal, population-based study of multiple determinants of health outcomes in an IBD cohort. Participants completed semi-annual surveys, and annual in-person interviews. Enquiries about the use of 12 types of CAM service providers and 13 CAM products, based on items from a national survey, were included at months 0, 12, 30 and 54. RESULTS: Overall, 74% of respondents used a CAM service or product in the 4.5-year period, with approximately 40% using some type of CAM at each time point, and 14% using CAM consistently at every time point. There was a trend for women to use CAM more than men; there was no difference in CAM use between patients with Crohn's disease and those with ulcerative colitis. The most often used CAM services (on average) were massage therapy (30%) and chiropractic (14%), physiotherapy (4%), acupuncture (3.5%) and naturopathy/homeopathy (3.5%). A wide range of CAM products were used, with Lactobacillus acidophilus (8%), fish and other oils (5.5%), glucosamine (4%) and chamomile (3.5%) as the most common. On average, only 18% of consumers used CAM for their IBD, so the majority chose it for other problems. There were no differences in psychological variables between CAM users and non-users. CONCLUSIONS: Those with IBD commonly try CAM, although very few use these approaches regularly over the years. CAM is not usually used by patients with IBD for disease management, but clinicians should be aware that many will test the services and products.

Obesity and malnutrition in children and adults: A clinical review.

Background: In the U.S., children and adults are consuming more low-nutrient foods with added sugar and excess fats as compared to healthy, high-quality calories and micronutrients. This diet is increasing the prevalence of malnutrition and nutritional deficiencies, despite high calorie intake. This is a review of the common micronutrient deficiencies, the risk factors for malnutrition, dietary plans, and the health consequences in children and adults with obesity in the U.S. Methods: This clinical review of literature was performed on the MEDLINE (PubMed) search engine. A total of 1391 articles were identified and after review, a total of 130 were found to be most pertinent. Discussion: The most common micronutrient deficiencies found in patients with obesity were vitamin A, thiamine (B1), folate (B9), cobalamin (B12), vitamin D, iron, calcium, and magnesium, especially prior and after bariatric surgery. Diets that produced the most weight reduction also further puts these individuals at risk for worsening malnutrition. Malnutrition and micronutrient deficiencies can worsen health outcomes if not properly managed. Conclusion: Adequate screening and awareness of malnutrition can improve the health outcomes in patients with obesity. Physiologic changes in response to increased adiposity and inadequate intake increase this population's risk of adverse health effects. Malnutrition affects the individual and contributes to worse public health outcomes. The recommendations for screening for malnutrition are not exclusive to individuals undergoing bariatric procedures and can improve the health outcomes of any patient with obesity. However, clearly, improved nutritional status can assist with metabolism and prevent adverse nutritional outcomes post-bariatric surgery. Clinicians should advise on proper nutrition and be aware of diets that worsen deficiencies.

Collaborating With Service Users to Select Psychiatry Residents Committed to Health Equity and Social Justice.

PROBLEM: Advocates have called for health services to be delivered equitably to all. Academic psychiatry must play a role in this work, given its history of creating and perpetuating the marginalization of people experiencing mental health issues. While medical educators have started teaching concepts such as structural competency and cultural safety, careful consideration of who enters the medical workforce and what values they bring is also important. APPROACH: The authors report on the first 5 years (2016-2021) of a collaboration with individuals who have used mental health or addiction services or identify as having lived experiences of mental health and/or substance use issues (i.e., service users) to select residents to the general adult psychiatry residency program at the University of Toronto who are committed to working toward health equity and social justice and who bring diverse personal, academic, and community-based experiences. Starting in 2016, a working group of service users and faculty iteratively refined the selection process to add personal letter and interview day writing sample prompts centered on social justice and advocacy. OUTCOMES: The working group, coled by service users since 2019, defined the problem (lack of attention to health equity and social justice in resident selection) and codesigned the solution by revising writing prompts used in the selection process and their assessment rubrics to emphasize these missing areas. Further, service users directly participated in the implementation by reviewing candidates' personal letters and interview day writing samples alongside faculty and residents. This work serves as an example of meaningful service user engagement in action. NEXT STEPS: To ensure the needs of service users are prioritized, future work must aim for long-term institutional commitment to strengthen service user involvement and power sharing with service user communities in resident selection and at other points along the medical education pathway.

Longitudinal change in bone mineral density in a population-based cohort of patients with inflammatory bowel disease.

Persons with inflammatory bowel disease (IBD) are reported to have a high prevalence of osteoporosis and reduced bone mineral density (BMD) and to be at higher risk of fracture. The course of BMD loss over time is poorly characterized in persons with IBD. Eighty-six persons, stratified by age, were enrolled from a population-based longitudinal IBD cohort study to undergo BMD testing at baseline, with final BMD testing a mean of 4.3 years later. The proportion of subjects with significant change in BMD at the lumbar spine, total hip, and femoral neck was assessed, as were clinical, biochemical, and anthropomorphic changes. Vertebral radiographs were also obtained at baseline and at the end of follow-up in those aged 50 years and above to detect vertebral fractures. The change in BMD seen in this cohort of IBD patients was similar to the expected rate of BMD loss in the general population. Age >50 years, decreasing body mass index (BMI), and corticosteroid use were most notably correlated with BMD loss. Subjects aged <50 years did not have statistically significant declines in BMD. IBD symptom activity scores correlated poorly with BMD loss. Vertebral fractures were uncommon, with only two subjects out of 41 >50 years old developing a definite radiographic fracture over the course of follow-up. No major nonvertebral fractures were observed. Patients with IBD do not appear to have significantly accelerated BMD loss. Older age, decreasing BMI, and corticosteroid use may identify IBD patients at greater risk for BMD loss.

Isostructural series of nine-coordinate chiral lanthanide complexes based on triazacyclononane.

Nonadentate ligands based on triazacyclononane incorporating pyridyl-2-phosphinate groups form an isostructural series of complexes with Ln ions in the solid state and in solution. The Ln ion is effectively shielded from the solvent environment. Crystal structures reveal a rigid C(3)-symmetric tricapped trigonal-prismatic coordination geometry that is maintained in solution for the methyl and phenylphosphinate series, as shown by multinuclear NMR analysis. Variable-temperature measurements of the field dependence of the water proton relaxivity in gadolinium complexes indicate that these systems exclude solvent from the primary coordination environment and minimize the second sphere of solvation. The electronic relaxation time for the gadolinium methylphosphinate complex has been estimated to be 550 (±150) ps by EPR and NMR methods, compared to values of around 0.30-0.05 ps for the terbium-ytterbium series, deduced by analyzing the field dependence (4.7-16.5 T) of the (31)P NMR longitudinal relaxation times. Values are compared with analogous azacarboxylate ligand complexes, supporting a key role for donor atom polarizability in determining the electronic relaxation. Spectral emission behavior in solution of samarium, europium, terbium, and dysprosium complexes is compared, and the resolved RRR-Λ and SSS-Δ complexes show strong circularly polarized luminescence. The molecular quadratic hyperpolarizability 〈ß(HLS)〉 has been measured in solution using hyper-Raleigh light-scattering methods, for the whole series of lanthanide complexes of one ligand. The values of 〈ß(HLS)〉 reach a maximum around the center of the series and are not simply dependent on the number of f electrons, suggesting a dominant contribution from the octupolar rather than the dipolar term.

Measures of relative importance for health-related quality of life.

PURPOSE: In health-related quality of life (HRQOL) studies, data are often collected on multiple domains for two or more groups of study participants. Quantitative measures of relative importance, which are used to rank order the domains based on their ability to discriminate between groups, are an alternative to multiple tests of significance on the group differences. This study describes relative importance measures based on logistic regression (LR) and multivariate analysis of variance (MANOVA) models. METHODS: Relative importance measures are illustrated using data from the Manitoba Inflammatory Bowel Disease (IBD) Cohort Study. Study participants with self-reported active (n = 244) and inactive (n = 105) disease were compared on 12 HRQOL domains from the Inflammatory Bowel Disease Questionnaire (IBDQ) and Medical Outcomes Study 36-item Short-Form (SF-36) Questionnaire. RESULTS: All but two relative importance measures ranked the IBDQ bowel symptoms and emotional health domains as most important. CONCLUSIONS: MANOVA-based importance measures are recommended for multivariate normal data and when group covariances are equal, while LR measures are recommended for non-normal data and when the correlations among the domains are small. Relative importance measures can be used in exploratory studies to identify a small set of domains for further research.

The information needs and preferences of persons with longstanding inflammatory bowel disease.

BACKGROUND: Understanding the information needs and preferred vehicles of information delivery to patients with inflammatory bowel disease (IBD) will enhance their care. OBJECTIVE: To survey persons with longstanding IBD as to their information needs and preferred vehicles of information delivery. METHODS: The population-based Manitoba IBD Cohort (n=271, mean disease duration 11 years) was surveyed to assess its information needs across 23 issues, both retrospectively at the time of diagnosis and currently. RESULTS: Most participants (64%) were initially diagnosed by a gastroenterologist, or otherwise by a family physician (19%) or surgeon (12%). Recalling time of diagnosis, at least 80% rated as very important information about common symptoms of IBD, possible complications, long-term prognosis, medication side effects, self management of symptoms and when to involve the doctor, yet only 10% to 36% believed they received the right amount of information about these issues. Dietary guidance was also regarded as important by 80% to 89%, yet only 8% to 16% received the correct amount of information. Regarding current needs, a large proportion believed it would be very helpful to have more information about long-term prognosis (66%) and diet considerations (60% to 68%). The following information sources were regarded as very acceptable: medical specialist (81%); brochure (79%); family doctor (64%); and website (64%), with 51% ranking the medical specialist as the first choice. In a comparison of the responses of this cohort to those of a recently diagnosed sample, there was remarkable consistency in the information needs and most desired sources of information. DISCUSSION: In the present population-based cohort with longstanding disease, dietary information was regarded as the least adequately addressed. There was clear openness to receiving information through other routes than just the medical specialist, suggesting that optimizing brochures and websites would be an important adjunct source of information. CONCLUSION: Approximately 10 years after diagnosis, only a small percentage of persons with IBD believed they received the correct amount of information about the issues they regarded as most important to have discussed at diagnosis.

Current practice in the measurement and interpretation of intervention adherence in randomised controlled trials: A systematic review.

BACKGROUND: Ideally all participants in a randomised controlled trial (RCT) should fully receive their allocated intervention; however, this rarely occurs in practice. Intervention adherence affects Type II error so influences the interpretation of trial results and subsequent implementation. We aimed to describe current practice in the definition, measurement, and reporting of intervention adherence in non-pharmacological RCTs, and how this data is incorporated into a trial's interpretation and conclusions. METHODS: We conducted a systematic review of phase III RCTs published between January 2018 and June 2020 in the National Institute for Health Research Journals Library for the Health Technology Assessment, Programme Grants for Applied Research, and Public Health Research funding streams. RESULTS: Of 237 reports published, 76 met the eligibility criteria and were included. Most RCTs (n = 68, 89.5%) reported adherence, though use of terminology varied widely; nearly three quarters of these (n = 49, 72.1%) conducted a sensitivity analysis. Adherence measures varied between intervention types: behavioural change (n = 10, 43.5%), psychological therapy (n = 5, 83.3%) and physiotherapy/rehabilitation (n = 8, 66.7%) interventions predominately measured adherence based on session attendance. Whereas medical device and surgical interventions (n = 17, 73.9%) primarily record the number of participants receiving the allocated intervention, a third (n = 33, 67.3%) of studies reported a difference in findings between primary and sensitivity analyses. CONCLUSIONS: Although most trials report elements of adherence, terminology was inconsistent, and there was no systematic approach to its measurement, analyses, interpretation, or reporting. Given the importance of adherence within clinical trials, there is a pressing need for a standardised approach or framework.

A review found small variable blocking schemes may not protect against selection bias in randomized controlled trials.

OBJECTIVE: Blocking is associated with prediction of the allocation sequence and subversion. This paper explores if blocking strategies lead to an increase in baseline age heterogeneity (a marker for potential subversion) and, whether the use of blocking is changing over time. STUDY DESIGN AND SETTINGS: The British Medical Journal, Journal of the American Medical Association, The Lancet and the New England Journal of Medicine were hand searched to identify open RCTs published in January between 2001 and 2020. To explore heterogeneity of baseline age meta-analyses were performed on trials implementing blocking, minimization, and simple randomization. RESULTS: One hundred seventy-nine open RCTs were identified: nine (5.0%) undertook simple randomization, 104 (58.1%) blocking, 25 (13.9%) minimization, and one (0.6%) both. Baseline age heterogeneity of 24% (P= 0.02) was observed in all trials implementing blocking, 62% (P = 0.001) in trials implementing a fixed block of four, 40% (P = 0.07) implementing variable blocks including a 2 and 0% for both simple randomization and minimization. Small block sizes are implemented in modern trials. CONCLUSION: Variable block sizes including two are associated with subversion and should not be implemented. If center only stratification is necessary, it should be used alongside larger blocking schemes. Authors should consider alternative methods to restrict randomization.