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The high cost of antimicrobials presents critical challenges for healthcare providers managing infections amidst the growing threat of antimicrobial resistance (AMR). High costs hinder access to necessary treatments, disproportionately affecting disadvantaged populations and exacerbating health disparities. High drug prices necessitate the use of less effective or more toxic alternatives, leading to suboptimal outcomes and prolonged hospitalizations. This, in turn, increases healthcare costs and undermines efforts to combat AMR. Equitable policies, national formularies, and cost caps for essential antimicrobials can ensure universal access to life-saving treatments and enable antimicrobial stewardship programs to ensure the best possible outcomes.
There is growing interest in lifestyle interventions as stand-alone and add-on therapies in mental health care due to their potential benefits for both physical and mental health outcomes. We evaluated lifestyle interventions focusing on physical activity, diet, and sleep in adults with severe mental illness (SMI) and the evidence for their effectiveness. To this end, we conducted a meta-review and searched major electronic databases for articles published prior to 09/2022 and updated our search in 03/2024. We identified 89 relevant systematic reviews and assessed their quality using the SIGN checklist. Based on the findings of our meta-review and on clinical expertise of the authors, we formulated seven recommendations. In brief, evidence supports the application of lifestyle interventions that combine behavioural change techniques, dietary modification, and physical activity to reduce weight and improve cardiovascular health parameters in adults with SMI. Furthermore, physical activity should be used as an adjunct treatment to improve mental health in adults with SMI, including psychotic symptoms and cognition in adults with schizophrenia or depressive symptoms in adults with major depression. To ameliorate sleep quality, cognitive behavioural informed interventions can be considered. Additionally, we provide an overview of key gaps in the current literature. Future studies should integrate both mental and physical health outcomes to reflect the multi-faceted benefits of lifestyle interventions. Moreover, our meta-review highlighted a relative dearth of evidence relating to interventions in adults with bipolar disorder and to nutritional and sleep interventions. Future research could help establish lifestyle interventions as a core component of mental health care.
The protection number of a vertex $v$ in a tree is the length of the shortest path from $v$ to any leaf contained in the maximal subtree where $v$ is the root. In this paper, we determine the distribution of the maximum protection number of a vertex in simply generated trees, thereby refining a recent result of Devroye, Goh, and Zhao. Two different cases can be observed: if the given family of trees allows vertices of outdegree $1$, then the maximum protection number is on average logarithmic in the tree size, with a discrete double-exponential limiting distribution. If no such vertices are allowed, the maximum protection number is doubly logarithmic in the tree size and concentrated on at most two values. These results are obtained by studying the singular behaviour of the generating functions of trees with bounded protection number. While a general distributional result by Prodinger and Wagner can be used in the first case, we prove a variant of that result in the second case.
Telerehabilitation and robotics, either traditional rigid or soft, have been extensively studied and used to improve hand functionality after a stroke. However, a limited number of devices combined these two technologies to such a level of maturity that was possible to use them at the patients’ home, unsupervised. Here we present a novel investigation that demonstrates the feasibility of a system that integrates a soft inflatable robotic glove, a cloud-connected software interface, and a telerehabilitation therapy. Ten chronic moderate-to-severe stroke survivors independently used the system at their home for 4 weeks, following a software-led therapy and being in touch with occupational therapists. Data from the therapy, including automatic assessments by the robot, were available to the occupational therapists in real-time, thanks to the cloud-connected capability of the system. The participants used the system intensively (about five times more movements per session than the standard care) for a total of more than 8 hr of therapy on average. We were able to observe improvements in standard clinical metrics (FMA +3.9 ± 4.0, p < .05, COPM-P + 2.5 ± 1.3, p < .05, COPM-S + 2.6 ± 1.9, p < .05, MAL-AOU +6.6 ± 6.5, p < .05) and range of motion (+88%) at the end of the intervention. Despite being small, these improvements sustained at follow-up, 2 weeks after the end of the therapy. These promising results pave the way toward further investigation for the deployment of combined soft robotic/telerehabilitive systems at-home for autonomous usage for stroke rehabilitation.
To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).
Participants and Methods:
Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.
Results:
pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).
Conclusions:
Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.
Routine patient care data are increasingly used for biomedical research, but such “secondary use” data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount.
Methods:
For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs.
Results:
We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives.
Conclusion:
After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.
Mathematical models of polyelectrolyte gels are often simplified by assuming the gel is electrically neutral. The rationale behind this assumption is that the thickness of the electric double layer (EDL) at the free surface of the gel is small compared to the size of the gel. Hence, the thin-EDL limit is taken, in which the thickness of the EDL is set to zero. Despite the widespread use of the thin-EDL limit, the solutions in the EDL are rarely computed and shown to match to the solutions for the electrically neutral bulk. The aims of this paper are to study the structure of the EDL and establish the validity of the thin-EDL limit. The model for the gel accounts for phase separation, which gives rise to diffuse interfaces with a thickness described by the Kuhn length. We show that the solutions in the EDL can only be asymptotically matched to the solutions for an electrically neutral bulk, in general, when the Debye length is much smaller than the Kuhn length. If the Debye length is similar to or larger than the Kuhn length, then phase separation can be initiated in the EDL. This phase separation spreads into the bulk of the gel and gives rise to electrically charged layers with different degrees of swelling. Thus, the thin-EDL limit and the assumption of electroneutrality only generally apply when the Debye length is much smaller than the Kuhn length.
Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood–brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated.
Aims
To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention.
Method
We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest.
Results
Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments.
Conclusions
The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed.
This chapter examines representations of American land and labour in the late nineteenth century as a complex engagement with the georgic mode. US writers used georgic representations of economic, technological and imperial expansion to promote widely divergent visions of the ideal citizen and worker, from the virtuous husbandman of Thomas Jefferson’s Notes on the State of Virginia (1785) to the bean-hoeing intellectual of Henry David Thoreau’s Walden (1854). Although the georgic mode represents themes central to US cultural history, it is not merely a celebration of industry and labour; like Virgil’s Georgics, which holds out the promise of progress in a fallen world but shows the human and environmental costs of the hard work it seems to promote, US adaptations of georgic illuminate the destructive aspect of agricultural labour and the moral ambiguities of imperial expansion and racialized labour.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
Objective: As health technology assessment (HTA) organizations in Canada and around the world seek to involve the public and patients in their activities, frameworks to guide decisions about whom to involve, through which mechanisms, and at what stages of the HTA process have been lacking. The aim of this study was to describe the development and outputs of a comprehensive framework for involving the public and patients in a government agency's HTA process.
Methods: The framework was informed by a synthesis of international practice and published literature, a dialogue with local, national and international stakeholders, and the deliberations of a government agency's public engagement subcommittee in Ontario, Canada.
Results: The practice and literature synthesis failed to identify a single, optimal approach to involving the public and patients in HTA. Choice of methods should be considered in the context of each HTA stage, goals for incorporating societal and/or patient perspectives into the process, and relevant societal and/or patient values at stake. The resulting framework is structured around four actionable elements: (i) guiding principles and goals for public and patient involvement (PPI) in HTA, (ii) the establishment of a common language to support PPI efforts, (iii) a flexible array of PPI approaches, and (iv) on-going evaluation of PPI to inform adjustments over time.
Conclusions: A public and patient involvement framework has been developed for implementation in a government agency’s HTA process. Core elements of this framework may apply to other organizations responsible for HTA and health system quality improvement.
In wild and domestic animals, gastrointestinal parasites can have significant impacts on host development, condition, health, reproduction and longevity. Improving our understanding of the causes and consequences of individual-level variation in parasite load is therefore of prime interest. Here we investigated the relationship between strongyle fecal egg count (FEC) and body condition in a unique, naturalized population of horses that has never been exposed to anthelmintic drugs (Sable Island, Nova Scotia, Canada). We first quantified variation in FEC and condition for 447 individuals according to intrinsic (sex, age, reproductive status, social status) and extrinsic (group size, location, local density) variables. We then quantified the repeatability of measurements obtained over a field season and tested for covariance between FEC and condition. FECs were high relative to other horse populations (mean eggs per gram ± SD = 1543·28 ± 209·94). FECs generally decreased with age, were higher in lactating vs non-lactating females, and unexpectedly lower in males in some part of the island. FECs and condition were both spatially structured, with patterns depending on age, sex and reproductive status. FECs and condition were both repeatable. Most notably, FECs and condition were negatively correlated, especially in adult females.
The polyphenol quercetin may prevent CVD due to its antihypertensive and vasorelaxant properties. We investigated the effects of quercetin after regular intake on blood pressure (BP) in overweight-to-obese patients with pre-hypertension and stage I hypertension. In addition, the potential mechanisms responsible for the hypothesised effect of quercetin on BP were explored. Subjects (n 70) were randomised to receive 162 mg/d quercetin from onion skin extract powder or placebo in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 6-week washout period. Before and after the intervention, ambulatory blood pressure (ABP) and office BP were measured; urine and blood samples were collected; and endothelial function was measured by EndoPAT technology. In the total group, quercetin did not significantly affect 24 h ABP parameters and office BP. In the subgroup of hypertensives, quercetin decreased 24 h systolic BP by −3·6 mmHg (P=0·022) when compared with placebo (mean treatment difference, −3·9 mmHg; P=0·049). In addition, quercetin significantly decreased day-time and night-time systolic BP in hypertensives, but without a significant effect in inter-group comparison. In the total group and also in the subgroup of hypertensives, vasoactive biomarkers including endothelin-1, soluble endothelial-derived adhesion molecules, asymmetric dimethylarginine, angiotensin-converting enzyme activity, endothelial function, parameters of oxidation, inflammation, lipid and glucose metabolism were not affected by quercetin. In conclusion, supplementation with 162 mg/d quercetin from onion skin extract lowers ABP in patients with hypertension, suggesting a cardioprotective effect of quercetin. The mechanisms responsible for the BP-lowering effect remain unclear.
Amid its human and material tolls, the Vietnam War has given rise to a curious enterprise—the complex process of recovering and repatriating the remains of U.S. service members Missing In Action (MIA) and presumed dead. In this trade, the bones that “count” are American and the aims underwriting the forensic efforts to return them are rooted in an ideology of national belonging.The resultant exchange of both knowledge and physical remains has developed through two historically intertwined ventures: state-sponsored casualty resolution efforts; and the much smaller, informal trafficking of skeletal remains, identification media, and information about American MIAs. This article examines how these sought-after bones tack between roles as objects of recovery, sale, or barter, scientific study, ritual burial, and public commemoration. Through their mutable worth, MIA remains illustrate the dynamic symbolism of war dead that evokes differing sensibilities about familiar or foreign soil, about care and belonging. Like the reliquiae of medieval Christianity, remains of missing service members, even in the most fragmentary form, are replete with the suggestion of power. Their pursuit depends on reciprocity. Indeed, more than just powerful symbols, these bones manifest and confer power itself, as caring for war dead demonstrates authority, and such authority falls to those who control access to the desired object, whether through formal or informal channels. Furthermore, power requires authentication, and the remains of missing American war dead become, in this system of circulation and exchange, a means to demonstrate knowledge, perform certainty, or exploit ambiguity.