Going Back in Time: Increasing Penicillin Susceptibility among Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children's and St. Louis Children's Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ ß-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin MIC determination. blaZ negative isolates with penicillin MIC ≤ 0.125 µg/mL were considered PSSA. Multilocus sequence typing (MLST) was conducted on a subset of isolates. A total of 329 unique isolates were included in the study. The median patient age was 9.2 years (IQR:5.1 to 12.2). Overall, 6.7% of isolates were penicillin susceptible. No PSSA were detected prior to 2015 but increased yearly thereafter. By the final study year, 20.4% of isolates were PSSA (P = 0.001). PSSA were similar to penicillin-resistant MSSA (PR-MSSA) isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. PSSA were of distinct sequence types compared to PR-MSSA. PSSA appears to be increasing among OAI in U.S. children. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. The potential for use of penicillin treatment in PSSA OAI warrants further study.

Hybrid Closed-Loop Insulin Pump Technology Can Be Safely Used in the Inpatient Setting.

BACKGROUND: Hybrid closed-loop (HCL) systems, also known as automated insulin delivery systems, are a rapidly growing technology in diabetes management. Because more patients are using these systems in the outpatient setting, it is important to also assess inpatient safety to determine whether HCL use can be continued when those patients become hospitalized. METHODS: The records of patients using HCL technology on admission to our hospital between June 1, 2020, and June 30, 2021, were analyzed. RESULTS: The final analysis included 71 patients divided into 3 categories based on their pump use as an inpatient: (1) HCL users; (2) manual pump users; and (3) pump removed. All cohorts were similar in age, sex, race, hemoglobin A1C at admission, and in Medicare Severity Diagnosis Related Group. Pairwise comparisons indicated that patient-stay mean glucose levels, frequency of patient-specific hyperglycemic measurements, and frequency of hypoglycemic events were similar between all groups. No adverse events, particularly occurrences of diabetic ketoacidosis, pump site complications or infection, or equipment malfunction, were reported. CONCLUSION: This preliminary case series review indicates that continued use of HCL technology in the hospital is safe. Moreover, glycemic control in HCL users was comparable with that in those using insulin pump with manual settings and those converted to basal-bolus insulin therapy.

Food for thought: Eating before saliva collection and interference with SARS-CoV-2 detection.

Saliva is a promising specimen for the detection of viruses that cause upper respiratory infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its cost-effectiveness and noninvasive collection. However, together with intrinsic enzymes and oral microbiota, children's unique dietary habits may introduce substances that interfere with diagnostic testing. To determine whether children's dietary choices impact SARS-CoV-2 molecular detection in saliva, we performed a diagnostic study that simulates testing of real-life specimens provided from healthy children (n = 5) who self-collected saliva at home before and at 0, 20, and 60 min after eating 20 foods they selected. Each of 72 specimens was split into two volumes and spiked with SARS-CoV-2-negative or SARS-CoV-2-positive clinical standards before side-by-side testing by reverse-transcription polymerase chain reaction matrix-assisted laser desorption ionization time-of-flight (RT-PCR/MALDI-TOF) assay. Detection of internal extraction control and SARS-CoV-2 nucleic acids was reduced in replicates of saliva collected at 0 min after eating 11 of 20 foods. Interference resolved at 20 and 60 min after eating all foods except hot dogs in one participant. This represented a significant improvement in the detection of nucleic acids compared to saliva collected at 0 min after eating (p = 0.0005). We demonstrate successful detection of viral nucleic acids in saliva self-collected by children before and after eating a variety of foods. Fasting is not required before saliva collection for SARS-CoV-2 testing by RT-PCR/MALDI-TOF, but waiting for 20 min after eating is sufficient for accurate testing. These findings should be considered for SARS-CoV-2 testing and broader viral diagnostics in saliva specimens.

Evaluating Cognitive-Linguistic Approaches to Interventions for Aphasia Within the Rehabilitation Treatment Specification System.

The Rehabilitation Treatment Specification System (RTSS) provides a framework to identify specific components of treatments developed within various rehabilitation disciplines (eg, physical, occupational, or speech-language therapy). Furthermore, this framework offers the opportunity to identify the target and active ingredients of a therapy approach as well as the mechanism of action by which it is hypothesized to effect change in abilities or functions. In this article, we apply the RTSS framework to the characterization of a sample of treatments for aphasia that are based on cognitive-linguistic models of language processing. Our discussion of these applications centers on the benefits of this classification system and additional criteria to consider when evaluating cognitive-linguistic treatments for aphasia.

Demystifying the Complexity of Aphasia Treatment: Application of the Rehabilitation Treatment Specification Systemx.

A considerable body of research supports the use of behavioral communication treatment as the standard of care for aphasia. In spite of robust progress in clinical aphasiology, many questions regarding optimal care remain unanswered. One of the major challenges to progress in the field is the lack of a common framework to adequately describe individual treatments, which, if available, would allow comparisons across studies as well as improved communication among researchers, clinicians, and other stakeholders. Here, we describe how aphasia treatment approaches can be systematically characterized using the Rehabilitation Treatment Specification System (RTSS). At the core of the RTSS is a tripartite structure that focuses on targets (the behavior that is expected to change as a result of treatment), ingredients (what a clinician does to affect change in the target), and mechanism(s) of action (why a given treatment works by linking the ingredients to the target). Three separate articles in the current issue specifically describe how the RTSS can be used to describe different kinds of aphasia treatment approaches: functional approaches, cognitive-linguistic approaches, and biological approaches. It is our hope that the application of the RTSS in clinical aphasiology will improve communication in published studies, grant proposals, and in the clinical care of persons with aphasia.

HOME2 Study: Household Versus Personalized Decolonization in Households of Children With Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infection-A Randomized Clinical Trial.

BACKGROUND: A household approach to decolonization decreases skin and soft tissue infection (SSTI) incidence, though this is burdensome and costly. As prior SSTI increases risk for SSTI, we hypothesized that the effectiveness of decolonization measures to prevent SSTI when targeted to household members with prior year SSTI would be noninferior to decolonizing all household members. METHODS: Upon completion of our 12-month observational Household Observation of Methicillin-resistant Staphylococcus aureus in the Environment (HOME) study, 102 households were enrolled in HOME2, a 12-month, randomized noninferiority trial. Pediatric index patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) SSTI, their household contacts, and pets were enrolled. Households were randomized 1:1 to the personalized (decolonization performed only by household members who experienced SSTI during the HOME study) or household (decolonization performed by all household members) approaches. The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily bleach-water baths. At 5 follow-up visits in participants' homes, swabs to detect S. aureus were collected from participants, environmental surfaces, and pets; incident SSTIs were ascertained. RESULTS: Noninferiority of the personalized approach was established for the primary outcome 3-month cumulative SSTI: 23 of 212 (10.8%) participants reported SSTI in household approach households, while 23 of 236 (9.7%) participants reported SSTI in personalized approach households (difference in proportions, -1.1% [95% confidence interval, -6.7% to 4.5%]). In multivariable analyses, prior year SSTI and baseline MRSA colonization were associated with cumulative SSTI. CONCLUSIONS: The personalized approach was noninferior to the household approach in preventing SSTI. Future studies should interrogate longer durations of decolonization and/or decontamination of the household environment to reduce household MRSA burden. CLINICAL TRIALS REGISTRATION: NCT01814371.

Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

Select methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce ß-lactamases with affinity for first-generation cephalosporins (1GCs). In the setting of a high inoculum, these ß-lactamases may promote the cleavage of 1GCs, a phenomenon known as the cefazolin inoculum effect (CzIE). We evaluated the prevalence and impact of CzIE on clinical outcomes among MSSA acute hematogenous osteomyelitis (AHO) cases. MSSA AHO isolates obtained from two children's hospitals between January 2011 and December 2018 were procured through ongoing surveillance studies. Isolates were tested for CzIE via a broth macrodilution assay using an inoculum of 107 CFU/ml; CzIE was defined as a cefazolin MIC of ≥16 µg/ml. Isolates were characterized by accessory gene regulator group (agr). The progression from acute to chronic osteomyelitis was considered an important outcome. A total of 250 cases with viable isolates were included. Notably, 14.4% of isolates exhibited CzIE with no observed temporal trend; and 4% and 76% of patients received a 1GC as an empirical and definitive therapy, respectively. CzIE isolates were more often resistant to clindamycin, belonged to agrIII, and associated with the development of chronic osteomyelitis. In multivariable analyses, agrIII, multiple surgical debridements, delayed source control, and CzIE were independently associated with progression to chronic osteomyelitis. A higher rate of chronic osteomyelitis was observed with CzIE isolates regardless of definitive antibiotic choice. CzIE is exhibited by 14.4% of MSSA AHO isolates in children. CzIE is independently associated with progression to chronic osteomyelitis in cases of AHO irrespective of final antibiotic choice. These data suggest that negative outcomes reported with CzIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure.

A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses.

BACKGROUND: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear. METHODS: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment. RESULTS: We enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention-to-treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P=0.73), and the cure rate in each active-treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P<0.001 for both comparisons). The results in the population of patients who could be evaluated were similar. This beneficial effect was restricted to participants with S. aureus infection. Among the participants who were initially cured, new infections at 1 month of follow-up were less common in the clindamycin group (15 of 221, 6.8%) than in the TMP-SMX group (29 of 215 [13.5%], P=0.03) or the placebo group (22 of 177 [12.4%], P=0.06). Adverse events were more frequent with clindamycin (58 of 265 [21.9%]) than with TMP-SMX (29 of 261 [11.1%]) or placebo (32 of 255 [12.5%]); all adverse events resolved without sequelae. One participant who received TMP-SMX had a hypersensitivity reaction. CONCLUSIONS: As compared with incision and drainage alone, clindamycin or TMP-SMX in conjunction with incision and drainage improves short-term outcomes in patients who have a simple abscess. This benefit must be weighed against the known side-effect profile of these antimicrobials. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00730028 .).

UK speech and language therapists' views and reported practices of discourse analysis in aphasia rehabilitation.

BACKGROUND: Discourse assessment and treatment in aphasia rehabilitation is a priority focus for a range of stakeholder groups. However, a significant majority of speech and language therapists (SLTs) infrequently conduct discourse analysis, and do not feel competent in doing so. Known barriers identified in other countries, specifically a lack of time, training, expertise and resources, affect use of discourse analysis in clinical practice. AIMS: To investigate UK SLTs' reported practices and views of discourse analysis, barriers and facilitators, and clinical feasibility in aphasia rehabilitation. METHODS & PROCEDURES: An online survey of 52 questions adapted from existing research and incorporating behaviour change literature was created for the study and piloted. UK SLTs working in aphasia rehabilitation for at least 6 months were invited to participate. Potential participants were contacted through national and local clinical excellence networks, a National Health Service (NHS) bespoke e-mail list, and national magazine advertisement, and the study was also advertised on social media (Twitter). Therapists read an online participant information sheet and submitted individual electronic consent online; then progressed to the Qualtrics survey. Descriptive, correlational and inferential statistical analyses were conducted, and content analysis was carried out on the questions requiring text. OUTCOMES & RESULTS: A total of 211 valid responses were received from primarily female SLTs, aged 20-40 years, working full-time in the NHS in England, in community, inpatient and acute/subacute multidisciplinary settings. A total of 30% SLTs collected discourse analysis often, were mostly very experienced, and working part-time in community settings. Years of experience was predictive of use. Discourse was most often collected using standardized picture descriptions and recounts during initial assessment. Samples were infrequently recorded, and typically transcribed in real-time. Most SLTs (53-95%) reported making clinical judgements or manually counted words, sentences, communication of ideas and errors, and were confident in doing so. Barriers included time constraints; lack of expertise, confidence, training, resources and equipment; and patient severity. Discourse 'super-users' were distinguished by significantly higher professional motivation for discourse and workplace opportunity than other SLTs, and 'non-users' were distinguished by significantly less knowledge and skills in discourse analysis than other SLTs. SLTs reported a desire and need for training, new/assistive tools and time to do more discourse analysis in practice. CONCLUSIONS & IMPLICATIONS: Clinicians were highly engaged and relatively active in at least some aspects of discourse analysis practice. Interventions that target individual clinicians as well as organizations and systems are needed to improve the uptake of discourse analysis in practice. What this paper adds What is already known on the subject? Discourse in aphasia rehabilitation is a priority in clinical practice and research. However, the majority of clinicians infrequently collect and analyse discourse. Research in Australia and the United States indicated that lack of time, assessment resources and relevant knowledge and skills are the main barriers to use. What this paper adds to existing knowledge Compared with existing research, UK SLTs were more likely to see discourse analysis as part of their role and experienced fewer barriers, and more SLTs did it at least sometimes in clinic. However, practices were limited by lack of training, giving rise to challenges in selecting and interpreting findings for clients. More use was predicted by more experience and commitment to discourse analysis, particularly where workplaces supported this approach. Less use was associated with less knowledge and skills in discourse analysis. Practice and decision-making were influenced by client factors and constrained to a lesser degree by logistical challenges. What are the potential or actual clinical implications of this study? Education and training in discourse analyses and in specific procedures are needed to improve individual clinicians' knowledge, skills and confidence in using discourse analysis for clients' rehabilitation. Equally, organizational and systems changes are needed to promote, support and reinforce discourse analysis in the workplace.

Choosing Discourse Outcome Measures to Assess Clinical Change.

Surveys of speech-language pathologists who work with people with aphasia indicate that they view the large number of existing measures to be a barrier to using discourse analysis in their practice. This article provides a process that can help determine whether a particular discourse outcome measure might be useful with a particular client. The process involves answering questions about the client, the treatment, the work setting, and the psychometric properties of the discourse outcome measure in question. By following this systematic process, clinicians can eliminate outcome measures that are not likely to provide useful data and can focus on those that can help them demonstrate treatment-related change.

Role of US LI-RADS in the LI-RADS Algorithm.

The US Liver Imaging Reporting and Data System (LI-RADS) was released in 2017 and is the newest of the four American College of Radiology (ACR) LI-RADS algorithms. US LI-RADS provides standardized terminology, technical recommendations, and a reporting framework for US examinations performed for screening or surveillance in patients at risk for developing hepatocellular carcinoma (HCC). The appropriate patient population for screening and surveillance includes individuals who are at risk for developing HCC but do not have known or suspected cancer. This includes patients with cirrhosis from any cause and subsets of patients with chronic hepatitis B virus infection in the absence of cirrhosis. In an HCC screening or surveillance study, US LI-RADS recommends assigning two scores that apply to the entire study: the US category, which determines follow-up, and a visualization score, which communicates the expected level of sensitivity of the examination but does not affect management. Three US categories are possible: US-1 negative, a study with no evidence of HCC; US-2 subthreshold, a study in which an observation less than 10 mm is depicted that is not definitely benign; and US-3 positive, a study in which an observation greater than or equal to 10 mm or a new thrombus in vein is identified, for which diagnostic contrast material-enhanced imaging is recommended. Three visualization scores are possible: A (no or minimal limitations), B (moderate limitations), and C (severe limitations). ©RSNA, 2019.

Asymptomatic Summertime Shedding of Respiratory Viruses.

To determine rates of both symptomatic and asymptomatic infection among ambulatory adults, we collected nasopharyngeal swab specimens, demographic characteristics, and survey information from 1477 adult visitors to a New York City tourist attraction during April-July 2016. Multiplex polymerase chain reaction analysis was used to identify specimens positive for common respiratory viruses. A total of 7.2% of samples tested positive for respiratory viruses; among positive samples, 71.0% contained rhinovirus, and 21.5% contained coronavirus. Influenza virus, respiratory syncytial virus, and parainfluenza virus were also detected. Depending on symptomatologic definition, 57.7%-93.3% of positive samples were asymptomatic. These findings indicate that significant levels of asymptomatic respiratory viral shedding exist during summer among the ambulatory adult population.

Impact of Systemic Antibiotics on Staphylococcus aureus Colonization and Recurrent Skin Infection.

Background: Staphylococcus aureus colonization poses risk for subsequent skin and soft tissue infection (SSTI). We hypothesized that including systemic antibiotics in the management of S. aureus SSTI, in conjunction with incision and drainage, would reduce S. aureus colonization and incidence of recurrent infection. Methods: We prospectively evaluated 383 children with S. aureus SSTI requiring incision and drainage and S. aureus colonization in the anterior nares, axillae, or inguinal folds at baseline screening. Systemic antibiotic prescribing at the point of care was recorded. Repeat colonization sampling was performed within 3 months (median, 38 days; interquartile range, 22-50 days) in 357 participants. Incidence of recurrent infection was ascertained for up to 1 year. Results: Participants prescribed guideline-recommended empiric antibiotics for purulent SSTI were less likely to remain colonized at follow-up sampling (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], .30-.79) and less likely to have recurrent SSTI (aHR, 0.57; 95% CI, .34-.94) than those not receiving guideline-recommended empiric antibiotics for their SSTI. Additionally, participants remaining colonized at repeat sampling were more likely to report a recurrent infection over 12 months (aHR, 2.37; 95% CI, 1.69-3.31). Clindamycin was more effective than trimethoprim-sulfamethoxazole (TMP-SMX) in eradicating S. aureus colonization (44% vs 57% remained colonized, P = .03) and preventing recurrent SSTI (31% vs 47% experienced recurrence, P = .008). Conclusions: Systemic antibiotics, as part of acute SSTI management, impact S. aureus colonization, contributing to a decreased incidence of recurrent SSTI. The mechanism by which clindamycin differentially affects colonization and recurrent SSTI compared to TMP-SMX warrants further study.

Comprehensive modeling reveals proximity, seasonality, and hygiene practices as key determinants of MRSA colonization in exposed households.

BACKGROUND: Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs). To develop interventions to prevent recurrent infections, household attributes and individual practices influencing S. aureus colonization must be discerned. METHODS: Households of healthy children with methicillin-resistant S. aureus (MRSA) SSTI (n = 150; 671 participants) were interviewed regarding health history, activities, and hygiene practices. S. aureus colonization was assessed in household members, and recovered isolates were typed by repetitive sequence-based PCR. RESULTS: The number of unique strain types in a household (median 1, range 0-7) correlated with the number of colonized individuals (p < 0.001). The MRSA infecting strain type colonized a household member in 57% of 91 households with an available infecting strain, and was the most common strain type recovered in 45% of these households. In multivariable models, household MRSA colonization burden (p < 0.001), sharing a bedroom with MRSA-colonized individuals (p = 0.03), renting dwelling (p = 0.048), and warmer seasons (p = 0.02) were associated with increased MRSA colonization. Increasing age (p = 0.02), bathing at least daily (p = 0.01), and antibacterial soap use (p = 0.03) correlated with reduced MRSA colonization. CONCLUSIONS: This study identified practices that correlate with MRSA colonization, which will inform physician counseling and multifaceted interventions among MRSA-affected households to mitigate MRSA in the community.

Semantic Treatments for Word and Sentence Production Deficits in Aphasia.

The cognitive domains of language and memory are intrinsically connected and work together during language processing. This relationship is especially apparent in the area of semantics. Several disciplines have contributed to a rich store of data about semantic organization and processing, and several semantic treatments for aphasic word and sentence production impairments have been based on these data. This article reviews the relationships between semantics and memory as they relate to word and sentence production, describes the aphasic language impairments that result from deficits in these areas, and summarizes treatment approaches that capitalize on what we have learned about these domains and how they work together.

An audit of first afebrile seizure management in an Irish tertiary pediatric setting.

UNLABELLED: The objective of this study was to compare the first afebrile seizure management with internationally recognized standards in an Irish tertiary pediatric setting. Twenty-one management standards were derived from a combination of British (NICE 2004) and North American (AAN 2003) guidelines. Cases of first afebrile seizure presenting to a pediatric emergency department between July 2007 and June 2010 were assessed against the standards. On completion, the standards developed were presented to the relevant stakeholders, a nurse-developed parental advice sheet was introduced, and a re-audit was performed from July 2010 to June 2011. Forty children were identified in the initial audit period (A1) and 41 over the re-audit (A2). No case achieved full compliance with the devised standards in the audit period. A median compliance score of 15 (range 5-20) was achieved in A1 and 17 (range 11-21) in A2 [mean rank 31.93 versus 49.85; p(1,1) < 0.0001]. Optimal compliance (total score of ≥17) with devised standards was achieved in 6/40 patients in A1 and in 21/41 patients in A2 [χ (2) = 11.95; p(1,1) = 0.001]. CONCLUSION: We demonstrated an initial lack of compliance with international guidelines on management of a common medical presentation, first afebrile seizure, and demonstrated that improvements can be achieved by identification of appropriate standards and critical appraisal of the compliance with these standards through both formal and informal education.

Care directed by a specialty-trained nurse practioner or physician assistant can overcome clinical inertia in management of inpatient diabetes.

OBJECTIVE: The study's objective was to determine the impact of care directed by a specialty-trained nurse practitioner (NP) or physician assistant (PA) on use of basal-bolus insulin therapy and glycemic control in a population of noncritically ill patients with diabetes. METHODS: A retrospective review of diabetes patients evaluated between July 1, 2011 and December 31, 2011 was conducted. Patients cotreated by a specialty-trained NP/PA were compared with patients who did not receive such care. RESULTS: In total, 171 patients with 222 hospitalizations were cotreated by an NP/PA and 543 patients with 665 hospitalizations were not. Patients with NP/PA involvement were younger, and had more frequent hyperglycemia, and had greater corticosteroid use than patients without NP/PA involvement (P<.01 for all). Basal-bolus insulin therapy was administered to 80% of patients with NP/PA involvement and 34% of patients without it (P<.01). After adjustment for age, sex, hyperglycemia measures, and corticosteroid use, the odds of basal-bolus insulin therapy being administered were increased significantly through NP/PA care (odds ratio, 3.66; 95% confidence interval, 2.36-5.67; P<.01). After adjustment for these variables and insulin regimen, NP/PA care was significantly correlated with lower mean point-of-care glucose levels at 24 hours before discharge (P = .042). CONCLUSION: Diabetes care assisted by an NP/PA trained in inpatient diabetes management results in greater use of recommended basal-bolus insulin therapy and is correlated with lower mean glucose levels before discharge. Adapting this model for use outside an endocrinology consult service needs to be explored so that the expertise can be brought to a broader inpatient population with diabetes.

Dietary and Lifestyle Factors of Brain Iron Accumulation and Parkinson's Disease Risk.

Purpose: Iron is an essential nutrient which can only be absorbed through an individual's diet. Excess iron accumulates in organs throughout the body including the brain. Iron dysregulation in the brain is commonly associated with neurodegenerative diseases like Alzheimer's disease and Parkinson's Disease (PD). Our previous research has shown that a pattern of iron accumulation in motor regions of the brain related to a genetic iron-storage disorder called hemochromatosis is associated with an increased risk of PD. To understand how diet and lifestyle factors relate to this brain endophenotype and risk of PD we analyzed the relationship between these measures, estimates of nutrient intake, and diet and lifestyle preference using data from UK Biobank. Methods: Using distinct imaging and non-imaging samples (20,477 to 28,388 and 132,023 to 150,603 participants, respectively), we performed linear and logistic regression analyses using estimated dietary nutrient intake and food preferences to predict a) brain iron accumulation score (derived from T2-Weighted Magnetic Resonance Imaging) and b) PD risk. In addition, we performed a factor analysis of diet and lifestyle preferences to investigate if latent lifestyle factors explained significant associations. Finally, we performed an instrumental variable regression of our results related to iron accumulation and PD risk to identify if there were common dietary and lifestyle factors that were jointly associated with differences in brain iron accumulation and PD risk. Results: We found multiple highly significant associations with measures of brain iron accumulation and preferences for alcohol (factor 7: t=4.02, pFDR=0.0003), exercise (factor 11: t=-4.31, pFDR=0.0001), and high-sugar foods (factor 2: t=-3.73, pFDR=0.0007). Preference for alcohol (factor 7: t=-5.83, pFDR<1×10-8), exercise (factor 11: t=-7.66, pFDR<1×10-13), and high sugar foods (factor 2: t=6.03, pFDR<1×10-8) were also associated with PD risk. Instrumental variable regression of individual preferences revealed a significant relationship in which dietary preferences associated with higher brain iron levels also appeared to be linked to a lower risk for PD (p=0.004). A similar relationship was observed for estimates of nutrient intake (p=0.0006). Voxel-wise analysis of i) high-sugar and ii) alcohol factors confirmed T2-weighted signal differences consistent with iron accumulation patterns in motor regions of the brain including the cerebellum and basal ganglia. Conclusion: Dietary and lifestyle factors and preferences, especially those related to carbohydrates, alcohol, and exercise, are related to detectable differences in brain iron accumulation and alterations in risk of PD, suggesting a potential avenue for lifestyle interventions that could influence risk.

A feasibility randomised waitlist-controlled trial of a personalised multi-level language treatment for people with aphasia: The remote LUNA study.

BACKGROUND: Stroke survivors with aphasia want to improve their everyday talking (discourse). In current UK practice, 90% of speech and language therapists believe discourse assessment and treatment is part of their role but are hampered by barriers in resources, time and expertise. There is a clinical need for well-articulated discourse assessment and treatments. LUNA is a multi-level treatment targeting words, sentences and discourse macrostructure in personal stories that addresses this clinical need. OBJECTIVES: This study aimed to assess the feasibility and acceptability of LUNA trial procedures in a randomised waitlist-controlled trial; and to evaluate preliminary efficacy. METHODS: This paper reports a phase II, waitlist-controlled, proof-of-concept feasibility trial. Participants with chronic aphasia (n = 28) were recruited from the community and randomised to an Immediate (n = 14) or Delayed (n = 14) group. LUNA treatment was delivered twice weekly for 10 weeks via the videoconferencing technology, Zoom. Feasibility was assessed in terms of participant recruitment and retention, adherence, missing data, and treatment fidelity. Preliminary treatment efficacy was assessed in terms of between group differences in outcome measures relating to discourse, language, and psychosocial state. RESULTS: The remote LUNA trial was feasible: 85% of those eligible consented to the trial; trial retention was 86%; 87% of treatment sessions were delivered as scheduled, and 79% of participants completed 80%+ of the treatment programme; data was missing only for participants who withdrew; treatment fidelity was high at 92% adherence; and only one clinical outcome measure demonstrated ceiling effects. ANCOVA analysis of the clinical outcome measures revealed group differences with medium and large effect sizes, indicating, improvements in the production of words, sentences, discourse macrostructure, overall language functioning (WAB-R), and psychosocial state (VAMS) following LUNA treatment. For most outcomes measured, similar treatment benefits were suggested in a secondary, non-parametric analysis. CONCLUSIONS: Large-scale evaluation of the clinical efficacy and cost-effectiveness of LUNA is warranted and supported by these findings. TRIAL REGISTRATION: Clinical trials registration: NCT05847023 (clinical trials.gov).