The Benefits and Challenges of Preconsent in a Multisite, Pediatric Sickle Cell Intervention Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133619/1/pbc26013.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133619/2/pbc26013_am.pd

Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in dogs and cats: a case-control study

Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in dogs and cats were investigated in an unmatched case-control study. A total of 197 animals from 150 veterinary practices across the United Kingdom was enrolled, including 105 MRSA cases and 92 controls with methicillin-susceptible S. aureus (MSSA) infection. The association of owners and veterinarian staff with the human healthcare sector (HCS) and animal-related characteristics such as signalment, antimicrobial and immunosuppressive therapy, and surgery were evaluated as putative risk factors using logistic regression. We found that significant risk factors for MRSA infection were the number of antimicrobial courses (p = 0.005), number of days admitted to veterinary clinics (p = 0.003) and having received surgical implants (p = 0.001). In addition, the odds of contact with humans which had been ill and admitted to hospital (p = 0.062) were higher in MRSA infected pets than in MSSA controls. The risk factors identified in this study highlight the need to increase vigilance towards identification of companion animal groups at risk and to advocate responsible and judicious use of antimicrobials in small animal practice

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Health and Wellness: Building Resilience in Deaf Bilingual Classrooms

Providing high quality health education programs in elementary schools has many benefits for students. It teaches students to be independent, allows students to focus more on their academics, and empowers students to live healthier lifestyles (CDC website, 2016). Unfortunately, there are no comprehensive physical and mental health curriculum available in American Sign Language that meet the needs of a wide variety of D/HH students. My curriculum titled “Health and Wellness: Building Resilience in Deaf Bilingual Classrooms'' is designed from a bilingual-bicultural lens and consists of two units. The first unit addresses how best to treat our bodies with good exercise and nutrition, and the second focuses on managing our mental health. The three curriculum goals include increasing vocabulary and content knowledge of health concepts in both ASL and English; practicing critical thinking skills to manage health; and setting health goals through writing in journals and recording ASL videos. The curriculum was implemented at the Washington School for the Deaf (WSD) in Vancouver, Washington from May 4, 2021 through June 10, 2021 in a 4th grade, in-person classroom with eight students. Findings from four different types of evidence (pre/post tests, teacher observations, student videos and student artifacts) show that despite being unable to complete the entire curriculum due to Covid-19 restrictions, students benefited from an enhanced understanding of health terms and concepts in ASL as well as a greater awareness of establishing health goals and using critical thinking skills to make healthier choices

Health and Wellness: Building Resilience in Deaf Bilingual Classrooms

Providing high quality health education programs in elementary schools has many benefits for students. It teaches students to be independent, allows students to focus more on their academics, and empowers students to live healthier lifestyles (CDC website, 2016). Unfortunately, there are no comprehensive physical and mental health curriculum available in American Sign Language that meet the needs of a wide variety of D/HH students. My curriculum titled “Health and Wellness: Building Resilience in Deaf Bilingual Classrooms'' is designed from a bilingual-bicultural lens and consists of two units. The first unit addresses how best to treat our bodies with good exercise and nutrition, and the second focuses on managing our mental health. The three curriculum goals include increasing vocabulary and content knowledge of health concepts in both ASL and English; practicing critical thinking skills to manage health; and setting health goals through writing in journals and recording ASL videos. The curriculum was implemented at the Washington School for the Deaf (WSD) in Vancouver, Washington from May 4, 2021 through June 10, 2021 in a 4th grade, in-person classroom with eight students. Findings from four different types of evidence (pre/post tests, teacher observations, student videos and student artifacts) show that despite being unable to complete the entire curriculum due to Covid-19 restrictions, students benefited from an enhanced understanding of health terms and concepts in ASL as well as a greater awareness of establishing health goals and using critical thinking skills to make healthier choices

Characteristics of COVID-19 clinical trials registered with ClinicalTrials.gov: cross-sectional analysis

Objectives To characterise current COVID-19-related research activities.Design Cross-sectional analysis.Setting Clinical trials registered with ClinicalTrials.gov testing interventions relevant to COVID-19.Data sources ClinicalTrials.gov was searched for COVID-19 and related terms to identify trials registered between 1 December 2019 and 1 May 2020 that test interventions related to the COVID-19 pandemic.Main outcome measures We classified trials according to intervention type, and report key trial characteristics including recruitment status, location, funder type, target enrolment number, intervention model (single group, randomised or sequential assignment) and projected completion date.Results Of the 630 identified clinical trials related to COVID-19, 509 (81%) involved the study of drugs or biological agents. Of these trials of drugs and biologics, 305 (60%) use an open-label design, 43 (8%) are single blinded (participant only) and 161 (32%) are double blinded (participant and investigator). 94 (18%) of the drug/biological trials are non-randomised. Either hydroxychloroquine or chloroquine is administered as part of the study protocol in 152 (30%) of the drug/biological trials. The total planned enrolment for these hydroxychloroquine/chloroquine trials is over 200 000 participants, which represents 65% of the total planned enrolment for all registered trials of drugs or biologics. There are also at least 25 registered trials of azithromycin (n=53), convalescent plasma (n=38), lopinavir/ritonavir (n=30), stem cell treatments (n=29) and tocilizumab (n=25). 142 trials were registered in the first 3 months of 2020, and 488 trials were registered between 1 April and 1 May 2020.Conclusions These findings demonstrate a robust research response to the COVID-19 pandemic, though many of the currently planned and ongoing trials focus on a small number of potential therapies, and many also lack essential design features and power necessary to provide accurate treatment effect estimates

Headache Disorders: Differentiating Primary and Secondary Etiologies

In the initial assessment of a headache patient, several dangerous secondary etiologies must be considered. A thorough history and physical examination, along with a comprehensive differential diagnosis may alert a physician to the diagnosis of a secondary headache particularly when it is accompanied by certain clinical features. Evaluation and workup include a complete neurological examination, consideration of neuroimaging, and serum/spinal fluid analysis if indicated. Careful attention to the patients’ history and physical examination will guide the diagnostic work-up and management. In this review, we summarize the diagnostic workup of various primary and secondary headache etiologies. Although most headaches are primary in nature, it is essential to screen for headache “red flags”, as they can suggest life threatening secondary etiologies. When secondary causes are suspected, appropriate neuroimaging can further differentiate the underlying cause. The appropriate imaging is dependent on the most likely secondary etiology, which is deduced from history and physical examination. When no red flags are present, primary headaches are more likely. These can be differentiated by frequency, location, duration, triggers, and presence of aura. The different clinical presentations for secondary headaches, as well as the distinguishing features for primary headaches are outlined in this review