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1.
J Adv Nurs ; 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38825956

ABSTRACT

AIM: To develop and psychometrically test the triage decision-making instrument, a tool to measure Emergency Department Registered Nurses decision-making. DESIGN: Five phases: (1) defining the concept, (2) item generation, (3) face validity, (4) content validity and (5) pilot testing. METHODS: Concept definition informed by a grounded theory study from which four domains emerged. Items relevant to the four domains were generated and revised. Face validity was established using three focus groups. The target population upon which the reliability and validity of the triage decision-making instrument was explored were triage registered nurses in emergency departments. Three expert judges assessed 89 items for content and domain designation using a 4-point scale. Psychometric properties were assessed by exploratory factor analysis, following which the names of the four domains were modified. RESULTS: The triage decision-making instrument is a 22-item tool with four factors: clinical judgement, managing acuity, professional collaboration and creating space. Focus group data indicated support for the domains. Expert review resulted in 46 items with 100% agreement and 13 with 66% agreement. Fifty-nine items were distributed to a convenience sample of 204 triage nurses from six hospitals in 2019. The Kaiser-Meyer-Olkin measures indicated that the data were sufficient for exploratory factor analysis. Bartlett's test indicated patterned relationships among the items (X2 (231) = 1156.69). An eigenvalue of >1.0 was used and four factors explained 48.64% of the variance. All factor loadings were ≥0.40. Internal consistency was demonstrated by Cronbach's alphas of .596 factor 1, .690 factor 2, .749 factor 3 and .822 for factor 4. CONCLUSION: The triage decision-making instrument meets the criteria for face validity, content validity and internal consistency. It is suitable for further testing and refinement. IMPACT: The instrument is a first step in quantifying triage decision-making in real-world clinical environments. The triage decision-making instrument can be used for targeted triage interventions aimed at improving throughput and staff education. STATISTICAL SUPPORT: Dr. Tak Fung who is a member of the research team is a statistician. STATISTICAL METHODS: Development, validation and assessment of instruments/scales. Descriptive statistics. REPORTING METHOD: STROBE cross-sectional checklist. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The TDI makes the complexity of triage decision-making visible. Identifying the influence of decision-making factors in addition to acuity that affect triage decisions will enable nurse managers and educators to develop targeted interventions and staff development initiatives. By extension, this will enhance patient care and safety.

2.
J Theor Biol ; 587: 111817, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38599566

ABSTRACT

The recent global COVID-19 pandemic resulted in governments enacting non-pharmaceutical interventions (NPIs) targeted at reducing transmission of SARS-CoV-2. But the NPIs also affected the transmission of viruses causing non-target seasonal respiratory diseases, including influenza and respiratory syncytial virus (RSV). In many countries, the NPIs were found to reduce cases of such seasonal respiratory diseases, but there is also evidence that subsequent relaxation of NPIs led to outbreaks of these diseases that were larger than pre-pandemic ones, due to the accumulation of susceptible individuals prior to relaxation. Therefore, the net long-term effects of NPIs on the total disease burden of non-target diseases remain unclear. Knowledge of this is important for infectious disease management and maintenance of public health. In this study, we shed light on this issue for the simplified scenario of a set of NPIs that prevent or reduce transmission of a seasonal respiratory disease for about a year and are then removed, using mathematical analyses and numerical simulations of a suite of four epidemiological models with varying complexity and generality. The model parameters were estimated using empirical data pertaining to seasonal respiratory diseases and covered a wide range. Our results showed that NPIs reduced the total disease burden of a non-target seasonal respiratory disease in the long-term. Expressed as a percentage of population size, the reduction was greater for larger values of the basic reproduction number and the immunity loss rate, reflecting larger outbreaks and hence more infections averted by imposition of NPIs. Our study provides a foundation for exploring the effects of NPIs on total disease burden in more-complex scenarios.


Subject(s)
COVID-19 , Epidemiological Models , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , Pandemics/prevention & control , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/prevention & control , Seasons , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Influenza, Human/transmission , Cost of Illness
3.
Math Biosci ; 369: 109131, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38113973

ABSTRACT

Research into the processes governing species richness has often assumed that the environment is fixed, whereas realistic environments are often characterised by random fluctuations over time. This temporal environmental stochasticity (TES) changes the demographic rates of species populations, with cascading effects on community dynamics and species richness. Theoretical and applied studies have used process-based mathematical models to determine how TES affects species richness, but under a variety of frameworks. Here, we critically review such studies to synthesise their findings and draw general conclusions. We first provide a broad mathematical framework encompassing the different ways in which TES has been modelled. We then review studies that have analysed models with TES under the assumption of negligible interspecific interactions, such that a community is conceptualised as the sum of independent species populations. These analyses have highlighted how TES can reduce species richness by increasing the frequency at which a species becomes rare and therefore prone to extinction. Next, we review studies that have relaxed the assumption of negligible interspecific interactions. To simplify the corresponding models and make them analytically tractable, such studies have used mean-field theory to derive fixed parameters representing the typical strength of interspecific interactions under TES. The resulting analyses have highlighted community-level effects that determine how TES affects species richness, for species that compete for a common limiting resource. With short temporal correlations of environmental conditions, a non-linear averaging effect of interspecific competition strength over time gives an increase in species richness. In contrast, with long temporal correlations of environmental conditions, strong selection favouring the fittest species between changes in environmental conditions results in a decrease in species richness. We compare such results with those from invasion analysis, which examines invasion growth rates (IGRs) instead of species richness directly. Qualitative differences sometimes arise because the IGR is the expected growth rate of a species when it is rare, which does not capture the variation around this mean or the probability of the species becoming rare. Our review elucidates key processes that have been found to mediate the negative and positive effects of TES on species richness, and by doing so highlights key areas for future research.


Subject(s)
Biodiversity , Ecosystem , Models, Theoretical , Probability
4.
Bull Math Biol ; 85(12): 124, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37962713

ABSTRACT

Many infectious diseases exist as multiple variants, with interactions between variants potentially driving epidemiological dynamics. These diseases include dengue, which infects hundreds of millions of people every year and exhibits complex multi-serotype dynamics. Antibodies produced in response to primary infection by one of the four dengue serotypes can produce a period of temporary cross-immunity (TCI) to infection by other serotypes. After this period, the remaining antibodies can facilitate the entry of heterologous serotypes into target cells, thus enhancing severity of secondary infection by a heterologous serotype. This represents antibody-dependent enhancement (ADE). In this study, we analyze an epidemiological model to provide novel insights into the importance of TCI and ADE in producing cyclic outbreaks of dengue serotypes. Our analyses reveal that without TCI, such cyclic outbreaks are synchronous across serotypes and only occur when ADE produces high transmission rates. In contrast, the presence of TCI allows asynchronous cycles of serotypes by inducing a time lag between recovery from primary infection by one serotype and secondary infection by another, with such cycles able to occur without ADE. Our results suggest that TCI is a fundamental driver of asynchronous cycles of dengue serotypes and possibly other multi-variant diseases.


Subject(s)
Coinfection , Dengue , Humans , Serogroup , Mathematical Concepts , Models, Biological , Dengue/epidemiology
5.
Mol Cell ; 83(21): 3904-3920.e7, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37879334

ABSTRACT

Lactate has long been considered a cellular waste product. However, we found that as extracellular lactate accumulates, it also enters the mitochondrial matrix and stimulates mitochondrial electron transport chain (ETC) activity. The resulting increase in mitochondrial ATP synthesis suppresses glycolysis and increases the utilization of pyruvate and/or alternative respiratory substrates. The ability of lactate to increase oxidative phosphorylation does not depend on its metabolism. Both L- and D-lactate are effective at enhancing ETC activity and suppressing glycolysis. Furthermore, the selective induction of mitochondrial oxidative phosphorylation by unmetabolized D-lactate reversibly suppressed aerobic glycolysis in both cancer cell lines and proliferating primary cells in an ATP-dependent manner and enabled cell growth on respiratory-dependent bioenergetic substrates. In primary T cells, D-lactate enhanced cell proliferation and effector function. Together, these findings demonstrate that lactate is a critical regulator of the ability of mitochondrial oxidative phosphorylation to suppress glucose fermentation.


Subject(s)
Energy Metabolism , Lactic Acid , Lactic Acid/metabolism , Electron Transport , Oxidative Phosphorylation , Glycolysis/physiology , Adenosine Triphosphate/metabolism
6.
bioRxiv ; 2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37577602

ABSTRACT

Lactate has long been considered a cellular waste product. However, we found that as extracellular lactate accumulates, it also enters the mitochondrial matrix and stimulates mitochondrial electron transport chain (ETC) activity. The resulting increase in mitochondrial ATP synthesis suppresses glycolysis and increases the utilization of pyruvate and/or alternative respiratory substrates. The ability of lactate to increase oxidative phosphorylation does not depend on its metabolism. Both L- and D-lactate are effective at enhancing ETC activity and suppressing glycolysis. Furthermore, the selective induction of mitochondrial oxidative phosphorylation by unmetabolized D-lactate reversibly suppressed aerobic glycolysis in both cancer cell lines and proliferating primary cells in an ATP-dependent manner and enabled cell growth on respiratory-dependent bioenergetic substrates. In primary T cells, D-lactate enhanced cell proliferation and effector function. Together, these findings demonstrate that lactate is a critical regulator of the ability of mitochondrial oxidative phosphorylation to suppress glucose fermentation.

8.
Nat Rev Mol Cell Biol ; 24(9): 651-667, 2023 09.
Article in English | MEDLINE | ID: mdl-37277471

ABSTRACT

Actin plays many well-known roles in cells, and understanding any specific role is often confounded by the overlap of multiple actin-based structures in space and time. Here, we review our rapidly expanding understanding of actin in mitochondrial biology, where actin plays multiple distinct roles, exemplifying the versatility of actin and its functions in cell biology. One well-studied role of actin in mitochondrial biology is its role in mitochondrial fission, where actin polymerization from the endoplasmic reticulum through the formin INF2 has been shown to stimulate two distinct steps. However, roles for actin during other types of mitochondrial fission, dependent on the Arp2/3 complex, have also been described. In addition, actin performs functions independent of mitochondrial fission. During mitochondrial dysfunction, two distinct phases of Arp2/3 complex-mediated actin polymerization can be triggered. First, within 5 min of dysfunction, rapid actin assembly around mitochondria serves to suppress mitochondrial shape changes and to stimulate glycolysis. At a later time point, at more than 1 h post-dysfunction, a second round of actin polymerization prepares mitochondria for mitophagy. Finally, actin can both stimulate and inhibit mitochondrial motility depending on the context. These motility effects can either be through the polymerization of actin itself or through myosin-based processes, with myosin 19 being an important mitochondrially attached myosin. Overall, distinct actin structures assemble in response to diverse stimuli to affect specific changes to mitochondria.


Subject(s)
Actins , Mitochondria , Actins/metabolism , Mitochondria/metabolism , Formins/metabolism , Myosins/metabolism , Endoplasmic Reticulum/metabolism
9.
Theor Popul Biol ; 149: 12-26, 2023 02.
Article in English | MEDLINE | ID: mdl-36521555

ABSTRACT

Neutral models in ecology assume that all species are demographically equivalent, such that their abundances differ ultimately because of demographic stochasticity rather than selection. In spite of their simplicity, neutral models have been found to accurately reproduce static patterns of biodiversity for diverse communities. However, the same neutral models have been found to exhibit species abundance dynamics that are far too slow compared to reality, resulting in poor fits to temporally dynamic patterns of biodiversity. Here, we show that one of the root causes of these slow dynamics is the additional assumption that a community has reached an equilibrium with a fixed community size, with species that have a net growth rate close to zero. We removed this additional assumption by constructing and analyzing a neutral model with an expected community size that can change over time and is not necessarily at equilibrium, which thus allows the historical formation of a community to be represented explicitly. Our analysis demonstrated that for the general scenario where a small community rapidly grows in size to a carrying capacity, representing recovery from ecological disturbance or assembly of a new community, the model produced much larger changes in species abundances and much shorter species ages than a neutral model at an equilibrium with fixed community size. In addition, the species abundance distribution was biphasic with a subset of abundant species arising from a founder effect. We confirmed these new results in applications of the new model to the specific scenario of recovery of the Amazon tree community after the end-Cretaceous bolide impact, which involved periods of increasing and decreasing community size. We conclude that incorporating transient dynamics in neutral models improves realism by allowing explicit consideration of how a community is formed over realistic time-scales.


Subject(s)
Models, Biological , Models, Theoretical , Population Dynamics , Biodiversity , Conservation of Natural Resources
10.
Surg Endosc ; 37(2): 1293-1302, 2023 02.
Article in English | MEDLINE | ID: mdl-36192659

ABSTRACT

BACKGROUND: Endoscopic submucosal dissection (ESD) has gained increasing popularity in the management of complicated colorectal polyps. However, clinical outcomes for ESD have remained highly inconsistent worldwide. This study investigated and analysed factors that significantly affect ESD outcomes. METHODS: We conducted a single-centred retrospective study on 220 colorectal polyps removed by ESD from 1st January 2016 to 31st December 2020. Data were collected and retrieved from clinical records. Variables studied included patient demographics, ESD technicalities and polyp characteristics. The primary outcome was completeness of resection based on en bloc and R0 resection rates. The secondary outcomes were recurrence, complications and hospital stay. Further analysis was performed for significant outcome determining factors. RESULTS: The en bloc resection and R0 resection rates were 97.3% and 65% respectively. Intraprocedural and delayed perforation rates were 3.2% and 0.5% respectively. Intraprocedural and delayed bleeding rates were both 1.8%. Post-polypectomy syndrome rate was 2.7%. The median hospital stay was 4 days. Submucosal fibrosis was a significant determining factor for lower en bloc resection (p = 0.004), lower R0 resection (p = 0.002), intraprocedural perforation (p = 0.001), intraprocedural bleeding (p = 0.025) and post-polypectomy syndrome (p = 0.039). Hybrid snaring was associated with lower en bloc resection (p < 0.001), while longer ESD time was associated with lower R0 resection (p = 0.003) and post-polypectomy syndrome (p = 0.025). Other significant factors for post-polypectomy syndrome included young age (p = 0.021) and large polyp size (p = 0.018). Secondary analysis showed that submucosal fibrosis was significantly associated with non-granular lesions (p < 0.001) and prior biopsy (p = 0.003). CONCLUSION: Submucosal fibrosis, hybrid snaring, ESD time, age and polyp size were significant outcome determining factors for ESD. By identifying these factors, strategies may be formulated to improve ESD outcomes.


Subject(s)
Colonic Diseases , Colonic Polyps , Colorectal Neoplasms , Endoscopic Mucosal Resection , Oral Submucous Fibrosis , Humans , Colorectal Neoplasms/surgery , Retrospective Studies , Postoperative Complications , Treatment Outcome
11.
J Cell Biol ; 221(11)2022 11 07.
Article in English | MEDLINE | ID: mdl-36102863

ABSTRACT

Mitochondrial damage represents a dramatic change in cellular homeostasis. One rapid response is perimitochondrial actin polymerization, termed acute damage-induced actin (ADA). The consequences of ADA are not understood. In this study, we show evidence suggesting that ADA is linked to rapid glycolytic activation upon mitochondrial damage in multiple cells, including mouse embryonic fibroblasts and effector CD8+ T lymphocytes. ADA-inducing treatments include CCCP, antimycin, rotenone, oligomycin, and hypoxia. The Arp2/3 complex inhibitor CK666 or the mitochondrial sodium-calcium exchanger (NCLX) inhibitor CGP37157 inhibits both ADA and the glycolytic increase within 5 min, supporting ADA's role in glycolytic stimulation. Two situations causing chronic reductions in mitochondrial ATP production, mitochondrial DNA depletion and mutation to the NDUFS4 subunit of complex 1 of the electron transport chain, cause persistent perimitochondrial actin filaments similar to ADA. CK666 treatment causes rapid mitochondrial actin loss and a drop in ATP in NDUFS4 knock-out cells. We propose that ADA is necessary for rapid glycolytic activation upon mitochondrial impairment, to re-establish ATP production.


Subject(s)
Actins , Adenosine Triphosphate , Mitochondria , Actins/metabolism , Adenosine Triphosphate/biosynthesis , Animals , CD8-Positive T-Lymphocytes , Cells, Cultured , Electron Transport Complex I/metabolism , Fibroblasts , Glycolysis , Mice , Mitochondria/metabolism , Mitochondria/pathology , Polymerization
12.
Curr Biol ; 32(7): 1577-1592.e8, 2022 04 11.
Article in English | MEDLINE | ID: mdl-35290799

ABSTRACT

Mitochondrial damage (MtD) represents a dramatic change in cellular homeostasis, necessitating metabolic changes and stimulating mitophagy. One rapid response to MtD is a rapid peri-mitochondrial actin polymerization termed ADA (acute damage-induced actin). The activation mechanism for ADA is unknown. Here, we use mitochondrial depolarization or the complex I inhibitor metformin to induce ADA. We show that two parallel signaling pathways are required for ADA. In one pathway, increased cytosolic calcium in turn activates PKC-ß, Rac, WAVE regulatory complex, and Arp2/3 complex. In the other pathway, a drop in cellular ATP in turn activates AMPK (through LKB1), Cdc42, and FMNL formins. We also identify putative guanine nucleotide exchange factors for Rac and Cdc42, Trio and Fgd1, respectively, whose phosphorylation states increase upon mitochondrial depolarization and whose suppression inhibits ADA. The depolarization-induced calcium increase is dependent on the mitochondrial sodium-calcium exchanger NCLX, suggesting initial mitochondrial calcium efflux. We also show that ADA inhibition results in enhanced mitochondrial shape changes upon mitochondrial depolarization, suggesting that ADA inhibits these shape changes. These depolarization-induced shape changes are not fragmentation but a circularization of the inner mitochondrial membrane, which is dependent on the inner mitochondrial membrane protease Oma1. ADA inhibition increases the proteolytic processing of an Oma1 substrate, the dynamin GTPase Opa1. These results show that ADA requires the combined action of the Arp2/3 complex and formin proteins to polymerize a network of actin filaments around mitochondria and that the ADA network inhibits the rapid mitochondrial shape changes that occur upon mitochondrial depolarization.


Subject(s)
Actins , Mitochondrial Proteins , Actin-Related Protein 2-3 Complex/metabolism , Actins/metabolism , Calcium/metabolism , Formins , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Polymerization
13.
Psychol Health ; 37(4): 440-456, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34038293

ABSTRACT

OBJECTIVE: The purpose of the pilot MOVE-C study was to examine the effects of a 12-week high-intensity interval training (HIIT) plus lifestyle education program on quality of life (QoL), behavioural and psychosocial outcomes among inactive adults with coeliac disease. DESIGN: This study used a 3 (time: baseline, immediately post and three months post) × 2 (group: experimental versus waitlist control) mixed design. After completing baseline testing, 41 participants were randomised to one of two groups: HIIT + or waitlist control (WLC). The HIIT + intervention involved twice-weekly HIIT, during which participants progressed to 14 × 30 s intervals (90% heart rate max; HRmax), with 2-minute recovery (50% HRmax). The HIIT + intervention also included six bi-weekly education sessions. RESULTS: Participants in HIIT + reported significant improvements in QoL and exercise behaviour immediately post-intervention, and this was sustained three months post-intervention, whereas no changes in QoL nor exercise behaviour were reported in WLC. Improvements were also reported among HIIT + immediately after the intervention for gastrointestinal symptoms and self-compassion. All participants reported significant improvements in adherence to a GFD immediately post-intervention. CONCLUSION: Findings from this pilot study provide preliminary evidence that a tailored exercise and lifestyle intervention can lead to improved QoL, exercise behaviour, gastrointestinal symptoms and self-compassion among inactive adults with coeliac disease.


Subject(s)
Celiac Disease , High-Intensity Interval Training , Adult , Cognition , Humans , Pilot Projects , Quality of Life
14.
Can J Neurol Sci ; 49(1): 109-117, 2022 01.
Article in English | MEDLINE | ID: mdl-33766169

ABSTRACT

OBJECTIVE: To assess demographic, clinical, and injury characteristics associated with health-related quality of life (HRQOL) in adults with persistent post-concussion symptoms (PPCS). METHODS: Adults with PPCS presenting to a specialized brain injury clinic completed demographic, injury, and clinical outcome questionnaires at the initial clinic assessment. Clinical outcome measures were collected including the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and the Fatigue Severity Scale (FSS). HRQOL was measured using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. Stepwise hierarchical multiple regression analysis adjusting for age, sex, and months since injury was used to determine associations between quality of life and clinical outcome measures. RESULTS: Overall, 125 participants were included. The PHQ-9, FSS, and GAD-7 were significant predictors of QOLIBRI scores (R2 = 0.481, p < .001), indicating that participants with higher levels of depressive symptoms, fatigue, and anxiety reported poorer HRQOL. The PHQ-9 score was the strongest predictor, accounting for 42.0% of the variance in QOLIBRI scores. No demographic or injury characteristics significantly predicted QOLIBRI scores. There was a high prevalence of depressive symptoms with 72.8% of participants having PHQ-9 scores ≥ 10. CONCLUSION: Among patients with PPCS, mental health and fatigue are important contributors to HRQOL. As there is a high burden of mood disorders and fatigue in this population, targeted treatments for these concerns may impact the quality of life.


Subject(s)
Brain Injuries , Post-Concussion Syndrome , Adult , Anxiety/etiology , Humans , Post-Concussion Syndrome/epidemiology , Quality of Life/psychology , Surveys and Questionnaires
15.
Explore (NY) ; 18(3): 335-341, 2022.
Article in English | MEDLINE | ID: mdl-34210638

ABSTRACT

BACKGROUND: The effects of integrated yoga programs on mental health outcomes in inflammatory bowel disease (IBD) have not been well explored. To explore the acceptability, implementation and effectiveness of an integrated eight-week yoga program plus aromatherapy massage in patients with IBD. METHODS: Nine participants with documented IBD were recruited from a gastroenterology clinic in Calgary, Alberta, Canada to participate in an integrated yoga program weekly for eight weeks with outcomes assessed at baseline and week 8. Primary outcomes were assessed using Theory of Planned Behaviour as a guiding theory to identify salient beliefs from qualitative analysis of a semi-structured interview, survey items measuring the strength of beliefs and a daily log was used to capture adherence and adverse events. Secondary outcomes were collected using validated survey tools examining anxiety, depression, stress, sleep quality, and physical and mental quality of life. RESULTS: Attitude, subjective norm and perceived behavioral control beliefs pertinent to the yoga intervention and daily practice were identified. Participants reported feeling the intervention was very helpful; however, felt guilt about not completing daily practices which decreased confidence and intention to continue with the practice. An average of 55.6% of in-person sessions were attended and decreased over time. Participants practiced on average of 5.4 days per week. Depression and mental health scores improved at week 8 from baseline. CONCLUSIONS: We were able to identify key salient beliefs of IBD patients in regard to an integrated yoga plus aromatherapy massage intervention. This intervention appears to be acceptable and further research should explore its potential to improve mental and physical health outcomes including IBD symptoms.


Subject(s)
Inflammatory Bowel Diseases , Yoga , Alberta , Chronic Disease , Humans , Inflammatory Bowel Diseases/therapy , Pilot Projects , Quality of Life , Yoga/psychology
16.
Pilot Feasibility Stud ; 7(1): 130, 2021 Jun 22.
Article in English | MEDLINE | ID: mdl-34158124

ABSTRACT

BACKGROUND: Post-traumatic headaches (PTH) are a common sequelae of traumatic brain injury (TBI) and greatly impact patient function and quality of life. Post-traumatic greater occipital neuralgia (GON) is a type of post-traumatic headache. Conventional treatment includes steroid/anesthetic injections which typically alleviate pain but have a short duration of effect. Platelet-rich plasma (PRP) is an emerging biological treatment for numerous degenerative disorders, including peripheral nerve disorders. The primary aim of this pilot study is to evaluate whether a randomized control trial of PRP for the treatment of GON in patients with post-traumatic headaches is feasible in regard to recruitment, adherence, retention, and adherence and adverse events. Exploratory aims include improvement in pain, function, and quality of life in patients with post-traumatic GON receiving PRP compared to steroid/anesthetic and normal saline injections. METHODS: Thirty adults (over 18 years of age) with post-traumatic GON will be randomized into one of three groups: (1) autologous PRP injection, (2) steroid/anesthetic injection (standard care), or (3) placebo injection with normal saline. Injections will be performed to the greater occipital nerve under ultrasound guidance by a trained physician. Daily headache intensity and frequency data will be collected pre-injection and for the duration of the study period. Feasibility will be defined as greater than 30% recruitment, 70% completion of intervention, 70% retention, and less than 2 minor adverse events. Exploratory outcomes will be explored using the Headache Impact Test-6 (HIT-6, a valid and reliable 6-item questionnaire for assessment of the impact of headaches across different diagnostic groups of headaches) and the quality of life in following brain injury questionnaire (QOILIBRI). DISCUSSION: This pilot study will be the first to evaluate the feasibility of PRP as a potential treatment of GON in patients with post-traumatic headache. TRIAL REGISTRATION: ClinicalTrials.gov - NCT04051203 (registered August 9, 2019).

17.
Arch Phys Med Rehabil ; 102(10): 1918-1925.e1, 2021 10.
Article in English | MEDLINE | ID: mdl-34044001

ABSTRACT

OBJECTIVE: To evaluate physical activity (PA) and sedentary behavior and their associations with symptom and quality of life outcomes in adults with persistent postconcussive symptoms (PPCS) after mild traumatic brain injury (mTBI). DESIGN: Cross-sectional cohort study. SETTING: Outpatient brain injury clinic. PARTICIPANTS: Consecutive sample of adults (N=180) with a diagnosis of mTBI and PPCS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PA and sedentary behavior were assessed using the Godin Leisure-Time Exercise Questionnaire and Rapid Assessment Disuse Index, respectively. Participants were dichotomized according to whether they completed 150 minutes of moderate-to-vigorous PA per week, based on Canadian guidelines. Postinjury moderate-to-vigorous PA was also analyzed as a continuous variable. RESULTS: Prior to injury, 85% of participants reported meeting PA guidelines, compared with 28% postinjury. Individuals meeting PA guidelines postinjury reported higher quality of life (η2p=0.130; P<.001) and lower scores on measures of functional impact of headache (η2p=0.065; P=.009), fatigue (η2p=0.080; P=.004), depression (η2p=0.085; P=.001), and anxiety (η2p=0.046; P=.031), compared with those not meeting guidelines. Sedentary behavior postinjury was negatively correlated with quality of life (rs[127]=-0.252; P=.004) and positively correlated with symptom burden (rs[167]=0.227; P=.003), fatigue (rs[127]=0.288; P=.001), depression (rs[174]=0.319; P<.001), and anxiety (rs[127]=0.180; P=.042). CONCLUSIONS: PA was significantly decreased in individuals with PPCS compared to preinjury levels. Meeting PA guidelines postinjury was associated with better clinical outcomes, suggesting that returning individuals to PA should be considered in the treatment of this patient population.


Subject(s)
Brain Injuries/physiopathology , Brain Injuries/psychology , Exercise Tolerance/physiology , Exercise/physiology , Post-Concussion Syndrome/physiopathology , Post-Concussion Syndrome/psychology , Sedentary Behavior , Adult , Cohort Studies , Cross-Sectional Studies , Female , Guideline Adherence , Humans , Male , Middle Aged , Quality of Life , Surveys and Questionnaires
18.
Sci Rep ; 11(1): 8534, 2021 04 20.
Article in English | MEDLINE | ID: mdl-33879807

ABSTRACT

Pituitary dysfunction, specifically growth hormone (GH) deficiency, can occur following traumatic brain injury. Our objective was to characterize the prevalence of GH deficiency (GHD) testing and response to recombinant human GH (rhGH) treatment in adults with persistent symptoms following mild traumatic brain injury (mTBI) referred for assessment of pituitary dysfunction. A retrospective chart review was conducted of patients seen at an outpatient brain injury clinic with a diagnosis of mTBI and persistent post-concussive symptoms who were referred to endocrinology. Clinical assessments of symptoms were collected. Investigations and results of GHD were collected, including initiation of rhGH treatment and treatment response. Of the 253 patients seen in both brain injury and endocrinology clinics, 97 with mTBI were referred for investigation of pituitary dysfunction and 73 (75%) had dynamic testing for assessment of GHD. Of the 26 individuals diagnosed with GHD, 23 (88%) started rhGH. GH therapy was inconsistently offered based on interpretation of GH dynamic testing results. Of those who started rhGH, 18 (78%) had a useful treatment response. This study suggests that clinical management of these patients is varied, highlighting a need for clear guidelines for the diagnosis and management of GHD following mTBI.


Subject(s)
Brain Concussion/metabolism , Growth Disorders/diagnosis , Growth Disorders/drug therapy , Human Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Insulin-Like Growth Factor I/metabolism , Post-Concussion Syndrome/metabolism , Adult , Female , Growth Disorders/etiology , Human Growth Hormone/blood , Humans , Male , Prevalence , Retrospective Studies , Treatment Outcome
19.
Langenbecks Arch Surg ; 406(2): 349-356, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33409579

ABSTRACT

PURPOSE: A defunctioning stoma is essential in reducing symptomatic leakage after colorectal surgery, particularly after lower anterior resection. Subsequent stoma closure is associated with morbidity and rarely mortality. This study aimed to identify the risk factors associated with post-operative complications related to stoma closure. METHODS: This retrospective cohort included patients who have undergone elective stoma closure between 2015 and 2017. Patient demographics, pre-morbidities, use of systemic therapy, stoma characteristics, and post-operative complications were retrieved from electronic records. Univariate and multivariate analysis was carried out to identify risk factors of stoma closure related morbidity. RESULTS: Ninety patients were included with a median age of 65 years, of which 58 (64.4%) of them were male. Sixty-nine (76.7%) patients had loop colostomy, while the rest had loop ileostomy. Fifty-four (60%) patients received neoadjuvant or adjuvant therapy. The median time interval from stoma creation to closure was 15 months. Nineteen (21.1%) patients had post-operative complications. The two most commonly observed post-operative complications were wound complications (16.7%) and intra-abdominal collections (6.7%). Fifteen (16.7%) patients developed an incisional hernia. The median follow-up time was 29 months. There was no 30-day mortality in this cohort. In multivariate analysis, adjuvant chemotherapy was associated with a higher risk of wound complications (p = 0.027). Higher risk of incisional hernia was seen in patients with history of hypertension (p = 0.046), use of adjuvant chemotherapy (p = 0.042) and stoma-related complications before closure (p = 0.002). Male patients might be associated with a higher risk of incisional hernia. CONCLUSION: Adjuvant chemotherapy is associated with a higher risk of post-operative complications, particularly with wound complications. Male patients, hypertension, adjuvant chemotherapy, and stoma-related complications are associated with a higher risk of incisional hernia.


Subject(s)
Colorectal Neoplasms , Rectal Neoplasms , Colorectal Neoplasms/surgery , Colostomy , Humans , Ileostomy/adverse effects , Infant, Newborn , Male , Morbidity , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
20.
Appl Physiol Nutr Metab ; 46(4): 325-336, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32961065

ABSTRACT

This study assessed the feasibility and benefits of high-intensity interval training (HIIT) plus lifestyle education among inactive adults with celiac disease. Forty-one participants were randomized to receive the intervention (HIIT plus lifestyle education; HIIT+) for 12 weeks or waitlist control (WLC). Testing was completed at baseline, immediately post-intervention, and 3 months post-intervention. Generalized estimating equations were used to assess changes in the outcome variables over time between the groups. Mean percent of age-predicted maximum heart rate was 97.9% and average rating of perceived exertion was 6.33 (out of 10) during HIIT intervals. Following the intervention, the HIIT+ showed enrichment in relative abundance of Parabacteroides and Defluviitaleaceae_UCG_011 while WLC showed enrichment in relative abundance of Roseburia intestinalis, Klebsiella, and Adlercreutzia. A unique set of taxa were differentially abundant between the groups at 3 months post-intervention. HIIT+ participants experienced a reduction in resting heart rate (-6.6 bpm) immediately post-intervention compared with WLC. Further research is needed to establish an optimal HIIT protocol that may improve maximal oxygen uptake and metabolic syndrome biomarkers. Findings from this pilot study provide preliminary evidence that an HIIT intervention is feasible for inactive adults with celiac disease and leads to favourable changes in resting heart rate alongside potentially beneficial shifts in gut microbiota. Trial registration number: ClinicalTrials.gov number NCT03520244. Novelty: HIIT leads to potentially beneficial changes in the gut microbiota of adults with celiac disease. An HIIT exercise intervention is feasible and well tolerated for patients with celiac disease.


Subject(s)
Celiac Disease/therapy , Gastrointestinal Microbiome , High-Intensity Interval Training , Life Style , Adult , Feasibility Studies , Female , Heart Rate , Humans , Male , Middle Aged , Sedentary Behavior
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