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Despite their significant impact, comprehensive screenings and detailed analyses of per- and polyfluoroalkyl substance (PFAS) binding strengths at the orthosteric and allosteric sites of NRs are currently lacking. This study addresses this gap by focusing on the binding interaction analysis of both common and uncommon PFAS with the nuclear receptors (NRs) vitamin D receptor (VDR), peroxisome proliferator-activated receptor gamma (PPARγ), pregnane X receptor (PXR), and estrogen receptor alpha (ERα). Advanced docking simulations were used to screen 9507 PFAS chemicals at the orthosteric and allosteric sites of PPARγ, PXR, VDR, and ERα. All receptors exhibited strong binding interactions at the orthosteric and allosteric site with a significant number of PFAS. We verified the accuracy of the docking protocol through multiple docking controls and validations. A mixture modeling analysis indicates that PFAS can bind in various combinations with themselves and endogenous ligands simultaneously, to disrupt the endocrine system and cause carcinogenic responses. These findings reveal that PFAS can interfere with nuclear receptor activity by displacing endogenous or native ligands by binding to the orthosteric and allosteric sites. The purpose of this study is to explore the mechanisms through which PFAS exert their endocrine-disrupting effects, potentially leading to more targeted therapeutic strategies. Importantly, this study is the first to explore the binding of PFAS at allosteric sites and to model PFAS mixtures at nuclear receptors. Given the high concentration and persistence of PFAS in humans, this study further emphasizes the urgent need for further research into the carcinogenic mechanisms of PFAS and the development of therapeutic strategies that target nuclear receptors.
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Fluorocarbonos , Simulação de Acoplamento Molecular , Ligação Proteica , Receptores Citoplasmáticos e Nucleares , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/química , Humanos , Fluorocarbonos/química , Fluorocarbonos/metabolismo , Sítios de Ligação , Ligantes , Sítio Alostérico , Receptor de Pregnano X/metabolismo , Receptor de Pregnano X/química , Disruptores Endócrinos/química , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/farmacologia , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/químicaRESUMO
This study examined the effects of plyometric-based structured game active breaks on fundamental movement skills (FMS), muscular fitness, student self-perception, and teacher's rating of actual behaviour in Grade 3 and 4 students. Primary school children aged 8-10 years old, from four classes, were cluster-randomly assigned to an intervention group (IG) (n = 54) or a control group (CG) (n = 48). The IG participated in structured plyometric-based game active breaks for 7-10 minutes daily, for six consecutive weeks. The CG resumed their regular daily school routine. FMS were assessed with the Canadian Agility Movement Skills Assessment test, and muscular fitness with the standing long jump (SLJ), countermovement jump (CMJ), and seated medicine ball chest throw tests. The Self-Perception Profile for Children and the Teacher's Rating Scale of Child's Actual Behaviour assessed student self-perception and teacher's perception of student actual behaviour, respectively. A significant (p < 0.01) interaction group by time was observed, with greater improvements in the IG compared to the CG in FMS (%diff = 13.11, Æp2 = 0.12), SLJ (%diff = 6.67, Æp2 = 0.02), seated medicine ball chest throw (%diff = 4.69, Æp2 = 0.08), student social self-perception (%diff = 9.31, Æp2 = 0.10), student scholastic self-perception (%diff = 7.27, Æp2 = 0.10), and teacher perception of student social competence (%diff = 8.31, Æp2 = 0.05). No difference (p > 0.05) was found in other variables. Integrating plyometric-based structured game active breaks into primary school settings evidenced improvement in FMS, muscular fitness, student self-perception, and teacher's rating of student actual behaviour.
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This study investigated the relationship between early within-therapy probe naming performance and anomia therapy outcomes in individuals with aphasia. Thirty-four adults with chronic, post-stroke aphasia participated in the Aphasia Language Impairment and Functioning Therapy (Aphasia LIFT) programme, comprised of 48â h of comprehensive aphasia therapy. Sets of 30 treated and 30 untreated items identified at baseline were probed during impairment therapy which targeted word retrieval using a combined semantic feature analysis and phonological component analysis approach. Multiple regression models were computed to determine the relationship between baseline language and demographic variables, early within-therapy probe naming performance (measured after 3â h of impairment therapy) and anomia treatment outcomes. Early within-therapy probe naming performance emerged as the strongest predictor of anomia therapy gains at post-therapy and at 1-month follow-up. These findings have important clinical implications, as they suggest that an individual's performance after a brief period of anomia therapy may predict response to intervention. As such, early within-therapy probe naming may provide a quick and accessible tool for clinicians to identify potential response to anomia treatment.
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Anomia , Afasia , Adulto , Humanos , Anomia/etiologia , Anomia/terapia , Terapia da Linguagem , Afasia/etiologia , Afasia/terapia , Semântica , Idioma , Resultado do TratamentoRESUMO
OBJECTIVE: To describe the health characteristics, condition-specific measures, chronic disease risk factors, and healthcare and medication use over time of individuals with musculoskeletal conditions awaiting orthopaedic surgical consultation. Study importance: Musculoskeletal conditions are highly prevalent in the general population and often coexist with chronic diseases. However, little is documented about the overall health of this group. This study describes the health of these individuals, with particular emphasis on modifiable risk factors of chronic disease. STUDY TYPE: A repeated measures longitudinal cohort study of individuals referred for orthopaedic consultation across three time points (2014, 2015 and 2016). METHODS: This study was undertaken in the orthopaedic outpatient service of a public tertiary referral hospital in New South Wales, Australia. Participants were aged 18 years and older and were referred for and awaiting orthopaedic surgical consultation for a musculoskeletal condition (back, neck, hand or wrist pain, or hip or knee osteoarthritis). Measures included patient demographics, condition-specific indicators (e.g. pain, disability, quality of life [QoL]) and chronic disease risk factors (e.g., excess weight, smoking). RESULTS: The mean age of participants was 57.7 years, and 7.3% identified as Aboriginal and/or Torres Strait Islander. Back (43.1%) and knee (35.0%) pain were the most prevalent conditions. At baseline (N = 1052), participants reported moderate pain (mean numerical pain rating scale score of 6.4, standard deviation [SD] 2.4) and QoL (Physical Component Score of 32.7, SD 10.7; Mental Component Score of 46.6, SD 13.3). Chronic disease risk factors were highly prevalent, with 74.6% of participants having three or more. For most measures, there were only small changes over time. CONCLUSION: Individuals with musculoskeletal conditions who are awaiting orthopaedic surgical consultation have a complex clinical picture and numerous chronic disease risk factors. Given the modifiable nature of many of these risk factors, identifying and addressing them before or while awaiting consultation may improve the health of these individuals.
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Doenças Musculoesqueléticas , Encaminhamento e Consulta , Humanos , Masculino , Feminino , Doenças Musculoesqueléticas/epidemiologia , Pessoa de Meia-Idade , Estudos Longitudinais , Encaminhamento e Consulta/estatística & dados numéricos , New South Wales/epidemiologia , Idoso , Adulto , Fatores de Risco , Estudos de Coortes , Procedimentos Ortopédicos/estatística & dados numéricos , Qualidade de Vida , Doença Crônica , Ortopedia , Listas de EsperaRESUMO
Nucleic acid-based assays, such as polymerase chain reaction (PCR), that amplify and detect organism-specific genome sequences are a standard method for infectious disease surveillance. However, challenges arise for virus surveillance because of their genetic diversity. Here, we calculated the variability of nucleotides within the genomes of 10 human viral species in silico and found that endemic viruses exhibit a high percentage of variable nucleotides (e.g., 51.4% for norovirus genogroup II). This genetic diversity led to the variable probability of detection of PCR assays (the proportion of viral sequences that contain the assay's target sequences divided by the total number of viral sequences). We then experimentally confirmed that the probability of the target sequence detection is indicative of the number of mismatches between PCR assays and norovirus genomes. Next, we developed a degenerate PCR assay that detects 97% of known norovirus genogroup II genome sequences and recognized norovirus in eight clinical samples. By contrast, previously developed assays with 31% and 16% probability of detection had 1.1 and 2.5 mismatches on average, respectively, which negatively impacted RNA quantification. In addition, the two PCR assays with a lower probability of detection also resulted in false negatives for wastewater-based epidemiology. Our findings suggest that the probability of detection serves as a simple metric for evaluating nucleic acid-based assays for genetically diverse virus surveillance.IMPORTANCENucleic acid-based assays, such as polymerase chain reaction (PCR), that amplify and detect organism-specific genome sequences are employed widely as a standard method for infectious disease surveillance. However, challenges arise for virus surveillance because of the rapid evolution and genetic variation of viruses. The study analyzed clinical and wastewater samples using multiple PCR assays and found significant performance variation among the PCR assays for genetically diverse norovirus surveillance. This finding suggests that some PCR assays may miss detecting certain virus strains, leading to a compromise in detection sensitivity. To address this issue, we propose a metric called the probability of detection, which can be simply calculated in silico using a code developed in this study, to evaluate nucleic acid-based assays for genetically diverse virus surveillance. This new approach can help improve the sensitivity and accuracy of virus detection, which is crucial for effective infectious disease surveillance and control.
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Doenças Transmissíveis , Norovirus , Humanos , Norovirus/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , RNA Viral/genética , Nucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: White matter hyperintensities (WMH) are considered to contribute to diminished brain reserve, negatively impacting on stroke recovery. While WMH identified in the chronic phase after stroke have been associated with post-stroke aphasia, the contribution of premorbid WMH to the early recovery of language across production and comprehension has not been investigated. OBJECTIVE: To investigate the relationship between premorbid WMH severity and longitudinal comprehension and production outcomes in aphasia, after controlling for stroke lesion variables. METHODS: Longitudinal behavioral data from individuals with a left-hemisphere stroke were included at the early subacute (n = 37) and chronic (n = 28) stage. Spoken language comprehension and production abilities were assessed at both timepoints using word and sentence-level tasks. Magnetic resonance imaging (MRI) was performed at the early subacute stage to derive stroke lesion variables (volume and proportion damage to critical regions) and WMH severity rating. RESULTS: The presence of severe WMH explained an additional 18% and 25% variance in early subacute (t = -3.00, p = .004) and chronic (t = -3.60, P = .001) language comprehension abilities respectively, after controlling for stroke lesion variables. WMH did not predict additional variance of language production scores. CONCLUSIONS: Subacute clinical MRI can be used to improve prognoses of recovery of aphasia after stroke. We demonstrate that severe early subacute WMH add to the prediction of impaired longitudinal language recovery in comprehension, but not production. This emphasizes the need to consider different domains of language when investigating novel neurobiological predictors of aphasia recovery.
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Afasia , Acidente Vascular Cerebral , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Afasia/etiologia , Afasia/complicações , Idioma , Imageamento por Ressonância Magnética/métodosRESUMO
Poststroke aphasia typically results from brain damage to the left-lateralized language network. The contribution of the right-lateralized homologues in aphasia recovery remains equivocal. In this longitudinal observational study, we specifically investigated the role of right hemisphere structural connectome in aphasia recovery. Twenty-two patients with aphasia after a left hemispheric stroke underwent comprehensive language assessment at the early subacute and chronic stages. A novel structural connectometry approach, using multi-shell diffusion-weighted MRI data collected at the early subacute stage, was used to evaluate the relationship between right hemisphere white matter connectome and language production and comprehension abilities at early subacute stage. Moreover, we evaluated the relationship between early subacute right hemisphere white matter connectome and longitudinal change in language production and comprehension abilities. All results were corrected for multiple comparisons. Connectometry analyses revealed negative associations between early subacute stage right hemisphere structural connectivity and language production, both cross-sectionally and longitudinally (pFDR < .0125). In turn, only positive associations between right hemisphere structural connectivity and language comprehension were observed, both cross-sectionally and longitudinally (pFDR < .0125). Interhemispheric connectivity was highly associated with comprehension scores. Our results shed light on the discordant interpretations of previous findings, by providing evidence that while some right hemisphere white matter pathways may make a maladaptive contribution to the recovery of language, other pathways support the recovery of language, especially comprehension abilities.
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Afasia , Acidente Vascular Cerebral , Substância Branca , Humanos , Idioma , Imagem de Difusão por Ressonância MagnéticaRESUMO
Background: Childhood obesity remains a global public health priority due to the enormous burden it generates. Recent surveillance data suggests there has been a sharp increase in the prevalence of childhood obesity during the COVID-19 pandemic. The Cochrane review of childhood obesity prevention interventions (0-18 years) updated to 2015 is the most rigorous and comprehensive review of randomised controlled trials (RCTs) on this topic. A burgeoning number of high quality studies have been published since that are yet to be synthesised. Methods: An update of the Cochrane systematic review was conducted to include RCT studies in school-aged children (6-18 years) published to 30 June 2021 that assessed effectiveness on child weight (PROSPERO registration: CRD42020218928). Available cost-effectiveness and adverse effect data were extracted. Intervention effects on body mass index (BMI) were synthesised in random effects meta-analyses by setting (school, after-school program, community, home), and meta-regression examined the association of study characteristics with intervention effect. Findings: Meta-analysis of 140 of 195 included studies (183,063 participants) found a very small positive effect on body mass index for school-based studies (SMD -0·03, 95%CI -0·06,-0·01; trials = 93; participants = 131,443; moderate certainty evidence) but not after-school programs, community or home-based studies. Subgroup analysis by age (6-12 years; 13-18 years) found no differential effects in any setting. Meta-regression found no associations between study characteristics (including setting, income level) and intervention effect. Ten of 53 studies assessing adverse effects reported presence of an adverse event. Insufficient data was available to draw conclusions on cost-effectiveness. Interpretation: This updated synthesis of obesity prevention interventions for children aged 6-18 years, found a small beneficial impact on child BMI for school-based obesity prevention interventions. A more comprehensive assessment of interventions is required to identify mechanisms of effective interventions to inform future obesity prevention public health policy, which may be particularly salient in for COVID-19 recovery planning. Funding: This research was funded by the National Health and Medical Research Council (NHMRC), Australia (Application No APP1153479).
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Wastewater-based epidemiology (WBE), an emerging approach for community-wide COVID-19 surveillance, was primarily characterized at large sewersheds such as wastewater treatment plants serving a large population. Although informed public health measures can be better implemented for a small population, WBE for neighborhood-scale sewersheds is less studied and not fully understood. This study applied WBE to seven neighborhood-scale sewersheds (average population of 1471) from January to November 2021. Community testing data showed an average of 0.004 % incidence rate in these sewersheds (97 % of monitoring periods reported two or fewer daily infections). In 92 % of sewage samples, SARS-CoV-2 N gene fragments were below the limit of quantification. We statistically determined 10-2.6 as the threshold of the SARS-CoV-2 N gene concentration normalized to pepper mild mottle virus (N/PMMOV) to alert high COVID-19 incidence rate in the studied sewershed. This threshold of N/PMMOV identified neighborhood-scale outbreaks (COVID-19 incidence rate higher than 0.2 %) with 82 % sensitivity and 51 % specificity. Importantly, neighborhood-scale WBE can discern local outbreaks that would not otherwise be identified by city-scale WBE. Our findings suggest that neighborhood-scale WBE is an effective community-wide disease surveillance tool when COVID-19 incidence is maintained at a low level.
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COVID-19 , Vigilância Epidemiológica Baseada em Águas Residuárias , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Incidência , Esgotos , Águas ResiduáriasRESUMO
BACKGROUND: Several school-based interventions are effective in improving child diet and physical activity, and preventing excessive weight gain, and tobacco or harmful alcohol use. However, schools are frequently unsuccessful in implementing such evidence-based interventions. OBJECTIVES: 1. To evaluate the benefits and harms of strategies aiming to improve school implementation of interventions to address student diet, physical activity, tobacco or alcohol use, and obesity. 2. To evaluate the benefits and harms of strategies to improve intervention implementation on measures of student diet, physical activity, obesity, tobacco use or alcohol use; describe their cost or cost-effectiveness; and any harms of strategies on schools, school staff or students. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was between 1 September 2016 and 30 April 2021 to identify any relevant trials published since the last published review. SELECTION CRITERIA: We defined 'Implementation' as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any trial (randomised controlled trial (RCT) or non-randomised controlled trial (non-RCT)) conducted at any scale, with a parallel control group that compared a strategy to implement policies or practices to address diet, physical activity, overweight or obesity, tobacco or alcohol use by students to 'no intervention', 'usual' practice or a different implementation strategy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Given the large number of outcomes reported, we selected and included the effects of a single outcome measure for each trial for the primary (implementation) and secondary (student health behaviour and obesity) outcomes using a decision hierarchy. Where possible, we calculated standardised mean differences (SMDs) to account for variable outcome measures with 95% confidence intervals (CI). For RCTs, we conducted meta-analyses of primary and secondary outcomes using a random-effects model, or in instances where there were between two and five studies, a fixed-effect model. The synthesis of the effects for non-randomised studies followed the 'Synthesis without meta-analysis' (SWiM) guidelines. MAIN RESULTS: We included an additional 11 trials in this update bringing the total number of included studies in the review to 38. Of these, 22 were conducted in the USA. Twenty-six studies used RCT designs. Seventeen trials tested strategies to implement healthy eating, 12 physical activity and six a combination of risk factors. Just one trial sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials used multiple implementation strategies, the most common being educational materials, educational outreach and educational meetings. The overall certainty of evidence was low and ranged from very low to moderate for secondary review outcomes. Pooled analyses of RCTs found, relative to a control, the use of implementation strategies may result in a large increase in the implementation of interventions in schools (SMD 1.04, 95% CI 0.74 to 1.34; 22 RCTs, 1917 participants; low-certainty evidence). For secondary outcomes we found, relative to control, the use of implementation strategies to support intervention implementation may result in a slight improvement on measures of student diet (SMD 0.08, 95% CI 0.02 to 0.15; 11 RCTs, 16,649 participants; low-certainty evidence) and physical activity (SMD 0.09, 95% CI -0.02 to 0.19; 9 RCTs, 16,389 participants; low-certainty evidence). The effects on obesity probably suggest little to no difference (SMD -0.02, 95% CI -0.05 to 0.02; 8 RCTs, 18,618 participants; moderate-certainty evidence). The effects on tobacco use are very uncertain (SMD -0.03, 95% CIs -0.23 to 0.18; 3 RCTs, 3635 participants; very low-certainty evidence). One RCT assessed measures of student alcohol use and found strategies to support implementation may result in a slight increase in use (odds ratio 1.10, 95% CI 0.77 to 1.56; P = 0.60; 2105 participants). Few trials reported the economic evaluations of implementation strategies, the methods of which were heterogeneous and evidence graded as very uncertain. A lack of consistent terminology describing implementation strategies was an important limitation of the review. AUTHORS' CONCLUSIONS: The use of implementation strategies may result in large increases in implementation of interventions, and slight improvements in measures of student diet, and physical activity. Further research is required to assess the impact of implementation strategies on such behavioural- and obesity-related outcomes, including on measures of alcohol use, where the findings of one trial suggest it may slightly increase student risk. Given the low certainty of the available evidence for most measures further research is required to guide efforts to facilitate the translation of evidence into practice in this setting.
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Dieta , Nicotiana , Criança , Exercício Físico , Humanos , Obesidade/prevenção & controle , Políticas , Ensaios Clínicos Controlados Aleatórios como Assunto , Uso de TabacoRESUMO
Gender-related barriers to immunization are key targets to improve immunization coverage and equity. We used individual-level demographic and health survey data from 52 low- and middle-income countries to examine the relationship between women's social independence (measured by the Survey-based Women's emPowERment (SWPER) Global Index) and childhood immunization. The primary outcome was receipt of three doses of the diphtheria-tetanus-pertussis vaccine (DTP3) among children aged 12-35 months; we secondarily examined failure to receive any doses of DTP-containing vaccines. We summarized immunization coverage indicators by social independence tertile and estimated crude and adjusted summary measures of absolute and relative inequality. We conducted all analyses at the country level using individual data; median results across the 52 examined countries are also presented. In crude comparisons, median DTP3 coverage was 12.3 (95% CI 7.9; 16.3) percentage points higher among children of women with the highest social independence compared with children of women with the lowest. Thirty countries (58%) had a difference in coverage between those with the highest and lowest social independence of at least 10 percentage points. In adjusted models, the median coverage was 7.4 (95% CI 5.0; 9.1) percentage points higher among children of women with the highest social independence. Most countries (41, 79%) had statistically significant relative inequality in DTP3 coverage by social independence. The findings suggest that greater social independence for women was associated with better childhood immunization outcomes, adding evidence in support of gender-transformative strategies to reduce childhood immunization inequities.
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BACKGROUND: Published studies suggest physical recovery from the COVID-19 is complex, with many individuals experiencing persistent symptoms. There is a paucity of data investigating the longer-term trajectory of physical recovery from COVID-19. METHODS: A prospective longitudinal design was utilised to investigate the impact COVID-19 has on physical functioning at 10-weeks (T1), 6-months (T2) and 1-year (T3) post-hospital discharge. Objective measures of recovery included 6-Minute Walk Test Distance (6MWTD), frailty (Clinical Frailty Scale), quantification of falls following hospital-discharge, return to work status and exercise levels. Subjective markers included symptoms (COVID-19-Specific Patient Concerns Assessment), fatigue (Chalder Fatigue Score) and health-related quality of life (HrQOL) [Short-Form-36 Health Survey Questionnaire (SF-36-II)]. Univariate analysis was performed using t-test, Wilcoxon rank-sum, and Chi-squared test, paired analysis using one-way analysis of variance and Krustal Wallis testing and correlation analysis with Spearman correlation tests. RESULTS: Sixty-one subjects participated. Assessments were conducted at a median of 55 days(T1), 242 days(T2), and 430 days(T3) following hospital-discharge. 6MWTD improved significantly overtime (F = 10.3, p < 0.001) from 365(209)m at T1 to 447(85)m at T3, however remained below population norms and with no associated improvement in perceived exertion. Approximately half (n = 27(51%)) had returned to pre-diagnosis exercise levels at T3. At least one concern/symptom was reported by 74%, 59% and 64% participants at T1, T2 and T3 respectively. Fatigue was the most frequently reported symptom at T1(40%) and T2(49%), while issues with memory/concentration was the most frequently reported at T3(49%). SF-36 scores did not change in any domain over the study period, and scores remained lower than population norms in the domains of physical functioning, energy/vitality, role limitations due to physical problems and general health. Return-to-work rates are low, with 55% of participants returning to work in some capacity, and 31% of participants don't feel back to full-health at 1-year following infection. CONCLUSION: Hospitalised COVID-19 survivors report persistent symptoms, particularly fatigue and breathlessness, low HrQOL scores, sub-optimal exercise levels and continued work absenteeism 1-year following infection, despite some objective recovery of physical functioning. Further research is warranted to explore rehabilitation goals and strategies to optimise patient outcomes during recovery from COVID-19. CLINICAL MESSAGE: Hospitalised COVID-19 survivors report significant ongoing rehabilitation concerns 1-year following infection, despite objective recovery of physical functioning. Our findings suggest those who returned to exercise within 1-year may have less fatigue and breathlessness. The impact of exercise, and other rehabilitative strategies on physical functioning outcomes following COVID-19 should be investigated in future research.
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COVID-19 , Fragilidade , Estudos de Coortes , Dispneia , Fadiga/diagnóstico , Fadiga/epidemiologia , Humanos , Estudos Longitudinais , Estudos Prospectivos , Qualidade de VidaRESUMO
ABSTRACT: We conducted a complier average causal effect (CACE) analyses for 2 pragmatic randomised controlled trials. We aimed to assess the effectiveness of telephone-based lifestyle weight loss interventions compared with usual care among compliers. Participants from 2 trials with low back pain (n = 160) and knee osteoarthritis (n = 120) with a body mass index ≥27 kg/m2 were included. We defined adherence to the telephone-based lifestyle weight loss program as completing 60% (6 from 10) of telephone health coaching calls. The primary outcomes for CACE analyses were pain intensity (0-10 Numerical Rating Scale) and disability (Roland Morris Disability Questionnaire for low back pain and Western Ontario and McMaster Universities Osteoarthritis Index for knee osteoarthritis). Secondary outcomes were weight, physical activity, and diet. We used an instrumental variable approach to estimate CACE in compliers. From the intervention groups of the trials, 29% of those with low back pain (n = 23/80) and 34% of those with knee osteoarthritis (n = 20/60) complied. Complier average causal effect estimates showed potentially clinically meaningful effects, but with low certainty because of wide confidence intervals, for pain intensity (-1.4; 95% confidence interval, -3.1, 0.4) and small but also uncertain effects for disability (-2.1; 95% confidence interval, -8.6, 4.5) among compliers in the low back pain trial intervention compared with control but not in the knee osteoarthritis trial. Our findings showed that compliers of a telephone-based weight loss intervention in the low back pain trial generally had improved outcomes; however, there were inconsistent effects in compliers from the knee osteoarthritis trial. Complier average causal effect estimates were larger than intention-to-treat results but must be considered with caution.
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Dor Lombar , Osteoartrite do Joelho , Programas de Redução de Peso , Humanos , Estilo de Vida , Dor Lombar/terapia , Osteoartrite do Joelho/terapia , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Telefone , Redução de Peso , Programas de Redução de Peso/métodosRESUMO
BACKGROUND: Kidney functional reserve (KFR), the only clinical kidney stress test, is not routinely measured because the complexity of measurement has limited clinical application. We investigated the utility of plasma cystatin C (CysC) after oral protein loading (PL) to determine KFR in Stages 3 and 4 chronic kidney disease (CKD). METHODS: Following a 24-h low-protein diet, KFR was measured after oral protein by hourly plasma CysC and compared with simultaneous creatinine clearance (CrCl) and radionuclide 99technetium diethylenetriaminepentaacetatic acid (Tc-99m-DTPA) measured glomerular filtration rate (mGFR) measurement in an observational, single-centre cohort study of adults with CKD Stages 3 and 4. Subjects were followed for 3 years for fast (F) or slow (S) CKD progression, dialysis requirement or death or a combination of major adverse kidney events (MAKEs). RESULT: CysC, CrCl and Tc-99m-DTPA mGFR measurements of KFR in 19 CKD Stage 3 and 21 CKD Stage 4 patients yielded good agreement. KFR was not correlated with baseline kidney function. Eight CKD Stage 3 (42%) and 11 CKD Stage 4 (52%) subjects reached their lowest serum CysC concentration 4 h after PL. CysC KFR and baseline serum creatinine (sCr) predicted death or dialysis or MAKE-F with a respective area under the curve (AUC) of 0.73 [95% confidence interval (CI) 0.48-0.89] and 0.71 (95% CI 0.51-0.84). Including CysC KFR, age, baseline sCr and nadir CysC predicted a decrease in sCr-estimated GFR >1.2 mL/min/year (MAKE-S) with an AUC of 0.89. CONCLUSIONS: Serial CysC avoided timed urine collection and radionuclide exposure and yielded equivalent estimates of KFR. Serial CysC may facilitate monitoring of KFR in clinical practice.
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Cistatina C , Insuficiência Renal Crônica , Adulto , Biomarcadores , Estudos de Coortes , Creatinina , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Ácido Pentético , Diálise RenalAssuntos
COVID-19 , Vacinas , Vacinas contra COVID-19 , Humanos , Programas de Imunização , SARS-CoV-2RESUMO
BACKGROUND: It is unusual for a de novo eating disorder to emerge in late adulthood. Across a number of years, a number of patients were identified who experienced severe and unexpected weight loss post curative management of an upper abdominal cancer (i.e., cancer survivors). Each of the patients was readmitted to the tertiary surgical hospital due to complications of severe malnutrition. Each presentation was initially considered to have a major physical health problem (such as cancer recurrence). Each required extensive investigations and multidisciplinary team involvement and were later conceptualised as a new-onset (in later adulthood) eating disorder that emerged post curative cancer treatment. The team wished to better understand this group and/or characterise and/or inform the scientific community of this phenomena if not already well described. LITERATURE REVIEW: The review identified that the re-emergence of pre-existing eating disorders at the time of cancer treatment was described; however, there was no identification of similar new-onset in later adulthood cases of eating disorders in cancer survivors in the medical literature. REVIEW OF THE CASES: Once ethics and consent was obtained, then the clinical course of four complex individuals were reviewed, including the use of a multidisciplinary Delphi review process, to understand commonalities and then plot a common care pathway with potential intervention points. CASE PRESENTATIONS: Common factors identified among the four patients included the lack of a physical health (organic) cause to the weight loss and ongoing weight loss despite intense multidisciplinary care. All had abnormal attitudes and behaviours relating to food, nutritional rehabilitation and/or recovery. None returned to a healthy weight and/or healthy eating despite extensive team input. The presentations were ultimately conceptualised as having severe disordered eating behaviours and in at least three cases met criteria for a formal eating disorder. The cohort had similar psychosocial characteristics including low socioeconomic status and complex family dynamics. None had prior formal psychiatric care. The outcomes were poor; one patient died, another required admission to a specialist eating disorder admission with a subsequent relapsing remitting course, and the remaining two had complicated chronic courses. CONCLUSION: Similar cases may be underreported. If identified earlier, there may be a role for intervention to prevent high morbidity and mortality and to support clinical teams managing similar complex patients.
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Schools are identified as a key setting to influence children's and adolescents' healthy eating. This umbrella review synthesised evidence from systematic reviews of school-based nutrition interventions designed to improve dietary intake outcomes in children aged 6 to 18 years. We undertook a systematic search of six electronic databases and grey literature to identify relevant reviews of randomized controlled trials. The review findings were categorised for synthesis by intervention type according to the World Health Organisation Health Promoting Schools (HPS) framework domains: nutrition education; food environment; all three HPS framework domains; or other (not aligned to HPS framework domain). Thirteen systematic reviews were included. Overall, the findings suggest that school-based nutrition interventions, including nutrition education, food environment, those based on all three domains of the HPS framework, and eHealth interventions, can have a positive effect on some dietary outcomes, including fruit, fruit and vegetables combined, and fat intake. These results should be interpreted with caution, however, as the quality of the reviews was poor. Though these results support continued public health investment in school-based nutrition interventions to improve child dietary intake, the limitations of this umbrella review also highlight the need for a comprehensive and high quality systematic review of primary studies.
Assuntos
Comportamento do Adolescente , Comportamento Infantil , Dieta , Comportamento Alimentar , Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Serviços de Saúde Escolar , Adolescente , Criança , Ingestão de Alimentos , Meio Ambiente , Educação em Saúde , Humanos , Revisões Sistemáticas como Assunto , TelemedicinaRESUMO
There has been a proliferation of digital health interventions (DHIs) targeting dietary intake. Despite their potential, the effectiveness of DHIs are thought to be dependent, in part, on user engagement. However, the relationship between engagement and the effectiveness of dietary DHIs is not well understood. The aim of this review is to describe the association between DHI engagement and dietary intake. A systematic search of four electronic databases and grey literature for records published before December 2019 was conducted. Studies were eligible if they examined a quantitative association between objective measures of engagement with a DHI (subjective experience or usage) and measures of dietary intake in adults (aged ≥18 years). From 10,653 citations, seven studies were included. Five studies included usage measures of engagement and two examined subjective experiences. Narrative synthesis, using vote counting, found mixed evidence of an association with usage measures (5 of 12 associations indicated a positive relationship, 7 were inconclusive) and no evidence regarding an association with subjective experience (both studies were inconclusive). The findings provide early evidence supporting an association between measures of usage and dietary intake; however, this was inconsistent. Further research examining the association between DHI engagement and dietary intake is warranted.
Assuntos
Dieta/métodos , Tecnologia Digital/métodos , Promoção da Saúde/métodos , Adolescente , Adulto , Ingestão de Alimentos , Feminino , Humanos , Intervenção Baseada em Internet , Masculino , Pessoa de Meia-Idade , Ciências da Nutrição/métodos , Saúde Pública , Telemedicina/métodos , Adulto JovemRESUMO
The emergence of persistent symptoms following SARS-CoV-2 infection, known as long COVID, is providing a new challenge to healthcare systems. The cardinal features are fatigue and reduced exercise tolerance. Vitamin D is known to have pleotropic effects far beyond bone health and is associated with immune modulation and autoimmunity. We hypothesize that vitamin D levels are associated with persistent symptoms following COVID-19. Herein, we investigate the relationship between vitamin D and fatigue and reduced exercise tolerance, assessed by the Chalder Fatigue Score, six-minute walk test and modified Borg scale. Multivariable linear and logistic regression models were used to evaluate the relationships. A total of 149 patients were recruited at a median of 79 days after COVID-19 illness. The median vitamin D level was 62 nmol/L, with n = 36 (24%) having levels 30-49 nmol/L and n = 14 (9%) with levels <30 nmol/L. Fatigue was common, with n = 86 (58%) meeting the case definition. The median Borg score was 3, while the median distance covered for the walk test was 450 m. No relationship between vitamin D and the measures of ongoing ill-health assessed in the study was found following multivariable regression analysis. These results suggest that persistent fatigue and reduced exercise tolerance following COVID-19 are independent of vitamin D.