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1.
J Telemed Telecare ; : 1357633X241259525, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839244

RESUMO

OBJECTIVE: We compared the impact of accessing healthcare (1) by telehealth (via telephone or video) vs face-to-face; and (2) by telephone vs video telehealth care, on escalation to emergency care. METHODS: We searched Medline, Embase and Cochrane CENTRAL to 24 July 2023; and conducted a citation analysis on 19 September 2023. We included randomised controlled trials. Risk of bias was assessed using Cochrane Tool 2. We calculated risk ratios for dichotomous outcomes and standardised mean difference for continuous outcomes. RESULTS: Ten trials compared telehealth (five telephone, four video, one both) to face-to-face care. Six were overall low, three some concerns and one high risk of bias. There were no differences between telehealth and face-to-face for visits to the emergency department (RR 1.07, 95% CI 0.89 to 1.29), hospitalisations up to 12 months (RR 0.89, 95% CI 0.56 to 1.41), deaths or other adverse events. Costs of care were similar, as were patient satisfaction scores.Six trials compared telephone to video telehealth: three were overall low, two some concerns, and one high risk of bias. There were no differences between telephone and video for visits to the emergency department (RR 0.67, 95% CI 0.41 to 1.12), hospitalisations (RR 1.04, 95% CI 0.73 to 1.48), deaths, other adverse events, costs, or patient satisfaction. Healthcare provider satisfaction was high. CONCLUSIONS: Telehealth care - delivered by telephone or by video - may be an appropriate alternative to face-to-face provision of care, as it does not increase the likelihood of escalation of care to the emergency department for patients in primary care, hospital outpatients, post-discharge patients or residents in aged care.

2.
Gut Microbes ; 16(1): 2359691, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38825856

RESUMO

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is the remarkable diversity in the ExPEC pangenome across pathotypes, clades, and strains, with hundreds of genes associated with pathogenesis including toxins, adhesins, and nutrient acquisition systems. Further, ExPEC is intimately associated with human mucosal surfaces and has evolved creative strategies to avoid the immune system. This review summarizes previous and ongoing preclinical and clinical ExPEC vaccine research efforts to help identify key gaps in knowledge and remaining challenges.


Assuntos
Infecções por Escherichia coli , Vacinas contra Escherichia coli , Escherichia coli Extraintestinal Patogênica , Humanos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/imunologia , Escherichia coli Extraintestinal Patogênica/genética , Animais
3.
Pediatr Obes ; : e13143, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886982

RESUMO

BACKGROUND: Anti-obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining 'real-world' AOM effectiveness and characteristics predicting response is important. OBJECTIVES: We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response. METHODS: This was a retrospective cohort study among youth seen in a US academic-based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating-related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys. RESULTS: Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5-month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3- (p = 0.001) and 6-month (p < 0.001) reductions. CONCLUSIONS: Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors.

4.
Front Endocrinol (Lausanne) ; 15: 1369270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800488

RESUMO

Introduction: Obesity affects approximately 20% of U.S. youth. Anti-obesity medications (AOMs) are promising lifestyle modification adjuncts for obesity treatment, and topiramate is commonly prescribed in pediatric weight management clinics. It is important to determine "real-world" effectiveness of AOMs and, given shifts towards personalized approaches, characteristics potentially predicting better or worse response. We therefore sought to describe clinical effectiveness from topiramate plus lifestyle modification, and to determine if baseline phenotypic characteristics are associated with better or worse response. Methods: We performed a retrospective cohort study (2012-2020) among youth (<18 years old) followed in a U.S. academic-based weight management clinic. Baseline characteristics (i.e., body mass index (BMI), liver function tests, eating-related behaviors) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, percent %BMI change, weight) were determined through review of electronic health records and clinic intake survey data. Results: Among 282 youth prescribed topiramate plus lifestyle modifications (mean baseline age 12.7 years, %BMIp95 144%), %BMIp95 and percent BMI change were statistically significantly reduced at each time point (1.5-, 3-, 6-, and 12-month %BMIp95 reductions: -2.2, -3.9, -6.6, and -9.3 percentage points, respectively; percent BMI reduction: -1.2%, -1.9%, -3.2%, and -3.4%, respectively; all p<0.01). Considering multiple comparisons, no baseline characteristics statistically significantly predicted response at any time point. Conclusions: We found that topiramate plus lifestyle modification reduced %BMIp95 and BMI among youth in a weight management clinical setting, and that no baseline characteristics evaluated were associated with response. These results should be considered preliminary given the observational nature of this study, and prospective studies are needed to further characterize clinical effectiveness and identify and confirm potential predictors of response.


Assuntos
Fármacos Antiobesidade , Índice de Massa Corporal , Obesidade Infantil , Topiramato , Humanos , Topiramato/uso terapêutico , Feminino , Masculino , Adolescente , Criança , Estudos Retrospectivos , Obesidade Infantil/terapia , Obesidade Infantil/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Resultado do Tratamento , Estilo de Vida , Programas de Redução de Peso/métodos , Comportamento de Redução do Risco
5.
Diagn Microbiol Infect Dis ; 109(3): 116269, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38692201

RESUMO

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities. The overall identification concordance rate in 1276 positive blood cultures was 98.1%. The overall concordance for the presence of resistance markers was 98.2% and concordance for the absence of resistance markers was 100%. A majority of ePlex® results (69.5%) represented opportunities for potential antimicrobial stewardship intervention. High concordance rates between the ePlex® BCID panels and standard identification and susceptibility methods enable utilization of results to guide rapid antimicrobial optimization.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Hemocultura , Testes de Sensibilidade Microbiana , Humanos , Hemocultura/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Farmacorresistência Bacteriana/genética , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Genótipo
6.
Post Reprod Health ; 30(2): 95-116, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38743767

RESUMO

Unscheduled bleeding on hormone replacement therapy (HRT) can affect up to 40% of users. In parallel with the increase in HRT prescribing in the UK, there has been an associated increase in referrals to the urgent suspicion of cancer pathway for unscheduled bleeding. On behalf of the British Menopause Society (BMS) an expert review panel was established, including primary and secondary care clinicians with expertise in the management of menopause, with representatives from key related organisations, including the Royal College of Obstetricians & Gynaecologists, the British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Royal College of General Practitioners and Faculty of Sexual and Reproductive Health, and service development partners from NHS England and GIRFT (Getting it Right First Time). For each topic, a focused literature review was completed to develop evidence led recommendations, where available, which were ratified by consensus review within the panel and by guideline groups.


Assuntos
Terapia de Reposição Hormonal , Humanos , Feminino , Reino Unido , Terapia de Reposição Hormonal/métodos , Menopausa , Metrorragia/etiologia , Sociedades Médicas , Terapia de Reposição de Estrogênios/métodos , Obstetra
7.
CJEM ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38796807

RESUMO

OBJECTIVES: Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure. METHODS: Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure. RESULTS: Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I2 = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I2 = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22 days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent. CONCLUSIONS: For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies. REGISTRATION: Open Science Framework:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .


RéSUMé: OBJECTIFS: Les recommandations existantes suggèrent d'envisager des corticostéroïdes pour le traitement complémentaire de la cellulite, mais cela est basé sur un seul essai avec une faible certitude des preuves. L'objectif était de déterminer si les anti-inflammatoires (anti-inflammatoires non stéroïdiens [AINS], corticostéroïdes) comme traitement d'appoint de la cellulite améliorent la réponse clinique et la guérison. MéTHODES: Revue systématique et méta-analyse comprenant des essais contrôlés randomisés de patients atteints de cellulite traités avec des antibiotiques, indépendamment de l'âge, du sexe, de la gravité et du contexte, et une intervention d'anti-inflammatoires (AINS ou corticostéroïdes) contre placebo ou sans intervention. Medline (PubMed), Embase (via Elsevier) et Cochrane CENTRAL ont été recherchés de la création au 1er août 2023. L'extraction des données a été effectuée indépendamment par paires. Le risque de biais a été évalué à l'aide de l'outil Cochrane sur le risque de biais 2. Les données ont été regroupées à l'aide d'un modèle à effets aléatoires. Les principaux résultats sont le temps de réponse clinique et de guérison. RéSULTATS: Cinq études (n = 331) ont été incluses, toutes des études adultes. Trois essais ont indiqué le délai de réponse clinique. Il y avait un avantage avec l'utilisation d'un AINS par voie orale comme traitement d'appoint au jour 3 (risque ratio 1,81, 95%CI 1,42 à 2,31, I2 = 0%). Il n'y avait pas de différence entre les groupes au jour 5 (rapport de risque 1,19, IC à 95% 0,62 à 2,26), bien que l'hétérogénéité était élevée (I2 = 96 %). La guérison clinique a été rapportée par trois essais, et il n'y avait aucune différence entre les groupes à tous les points de temps jusqu'à 22 jours. L'hétérogénéité statistique était modérée à faible. Les événements indésirables (N = 3 essais) étaient peu fréquents. CONCLUSIONS: Pour les patients atteints de cellulite, les meilleures données disponibles suggèrent que les anti-inflammatoires non stéroïdiens oraux (AINS) comme traitement d'appoint aux antibiotiques peuvent entraîner une amélioration de la réponse clinique précoce, bien que cela ne soit pas soutenu au-delà de quatre jours. Les données sont insuffisantes pour commenter le rôle des corticostéroïdes dans la réponse clinique. Ces résultats doivent être interprétés avec prudence en raison du petit nombre d'études incluses. ENREGISTREMENT: Cadre de la science ouverte:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

8.
Med Teach ; : 1-10, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599334

RESUMO

BACKGROUND: Mandatory training is considered fundamental to establishing and maintaining high standards of professional practice. There is little evidence however, of the training either achieving its required learning outcomes, or delivering improvement in outcomes for patients. Whist organisations may be hitting their compliance target for mandatory training, is the purpose missing the point? This systematic review aims to synthesize and evaluate the efficacy of statutory and mandatory training. METHODS: PubMed, EMBASE, CNAHL, ERIC and Cochrane Central registers were searched on 23rd May 2023. All research designs were included and reported training had to specify an organisational mandate within a healthcare setting. Data was coded using a modified Kirkpatrick (KP) rating system. Critical appraisal was undertaken using the Modified Medical Education Research Study Quality Instrument, Critical Appraisal Skills Programme Qualitative Studies checklist and Mixed Methods Assessment Tool. RESULTS: Twenty-five studies were included, featuring 9132 participants and 1348 patient cases audited. Studies described evaluation of mandatory training according to Kirkpatrick's outcomes levels 1-4b, with the majority (68%) undertaken in the UK and within acute settings. Training duration varied from 5 min to 3 days. There is a lack of consensus regarding mandatory training rationale, core topics, duration, and optimum refresher training period. Currently, mandatory training does not consistently translate to widescale improvements in safe practice or improved patient outcomes. CONCLUSIONS: Due to the lack of international consensus regarding the need for mandated training, most papers originated from countries with centrally administered national health care systems. The rationale for mandating training programmes remains undefined. The assumption that mandatory training is delivering safe practice outcomes is not supported by studies included in this review. The findings of this review offer a basis for further research to be undertaken to assist with the design, facilitation, and impact of mandatory training.

9.
Infect Immun ; 92(5): e0044023, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38591882

RESUMO

Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Vacinas contra Escherichia coli , Escherichia coli Extraintestinal Patogênica , Proteínas Hemolisinas , Animais , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/imunologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/imunologia , Camundongos , Proteínas Hemolisinas/imunologia , Proteínas Hemolisinas/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/imunologia , Vacinas contra Escherichia coli/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética , Feminino , Fatores de Virulência/genética , Fatores de Virulência/imunologia , Sistemas de Secreção Tipo V/imunologia , Sistemas de Secreção Tipo V/genética , Modelos Animais de Doenças , Humanos
10.
Ann Intern Med ; 177(5): 643-655, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38588546

RESUMO

BACKGROUND: Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes. PURPOSE: To evaluate the long-term effects of salt substitution on cardiovascular outcomes. DATA SOURCES: PubMed, EMBASE, Cochrane CENTRAL, and CINAHL searched from inception to 23 August 2023. Trial registries, citation analysis, and hand-search were also done. STUDY SELECTION: Randomized controlled trials (RCTs) comparing provision of or advice to use a salt substitute with no intervention or use of regular salt among adults for 6 months or longer in total study duration. DATA EXTRACTION: Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes include mortality, major cardiovascular events (MACE), and adverse events at 6 months or greater. Secondary and post hoc outcomes include blood pressure, cause-specific mortality, and urinary excretion at 6 months or greater. Random-effects meta-analyses were done and certainty of effect estimates were assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). DATA SYNTHESIS: Of the 16 included RCTs, 8 reported on primary outcomes. Most (n = 7 of 8) were done in China or Taiwan, 3 were done in residential facilities, and 7 included populations of older age (average 62 years) and/or with higher-than-average cardiovascular risk. In this population, salt substitute may reduce risk for all-cause mortality (6 RCTs; 27 710 participants; rate ratio [RR], 0.88 [95% CI, 0.82 to 0.93]; low certainty) and cardiovascular mortality (4 RCTs; 25 050 participants; RR, 0.83 [CI, 0.73 to 0.95]; low certainty). Salt substitute may result in a slight reduction in MACE (3 RCTs; 23 215 participants; RR, 0.85 [CI, 0.71 to 1.00]; very low certainty), with very low-certainty evidence of serious adverse events (6 RCTs; 27 995 participants; risk ratio, 1.04 [CI, 0.87 to 1.25]). LIMITATIONS: The evidence base is dominated by a single, large RCT. Most RCTs were from China or Taiwan and involved participants with higher-than-average cardiovascular risk; therefore, generalizability to other populations is very limited. CONCLUSION: Salt substitution may reduce all-cause or cardiovascular mortality, but the evidence for reducing cardiovascular events and for not increasing serious adverse events is uncertain, particularly for a Western population. The certainty of evidence is higher among populations at higher cardiovascular risk and/or following a Chinese diet. PRIMARY FUNDING SOURCE: National Health and Medical Research Council. (PROSPERO: CRD42022327566).


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/mortalidade , Dieta Hipossódica , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hipertensão
11.
J Ovarian Res ; 17(1): 71, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566237

RESUMO

BACKGROUND: Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer. METHODS: We aimed to further test a humanized anti-STn-ADC in sialyl-Tn (STn) positive and negative ovarian cancer cell line, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. Furthermore, we sought to determine whether serum STn levels would reflect STn positivity in the tumor samples enabling us to identify patients that an anti-STn-ADC strategy would best serve. We developed a custom ELISA with high specificity and sensitivity, that was used to assess whether circulating STn levels would correlate with stage, progression-free survival, overall survival, and its value in augmenting CA-125 as a diagnostic. Lastly, we assessed whether the serum levels reflected what was observed via immunohistochemical analysis in a subset of tumor samples. RESULTS: Our in vitro experiments further define the specificity of the anti-STn-ADC. The ovarian cancer PDO, and PDX models provide additional support for an anti-STn-ADC-based strategy for targeting ovarian cancer. The custom serum ELISA was informative in potential triaging of patients with elevated levels of STn. However, it was not sensitive enough to add value to existing CA-125 levels for a diagnostic. While the ELISA identified non-serous ovarian tumors with low CA-125 levels, the sample numbers were too small to provide any confidence the STn ELISA would meaningfully add to CA-125 for diagnosis. CONCLUSIONS: Our preclinical data support the concept that an anti-STn-ADC may be a viable option for treating patients with elevated STn levels. Moreover, our STn-based ELISA could complement IHC in identifying patients with whom an anti-STn-based strategy might be more effective.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Humanos , Feminino , Antígenos Glicosídicos Associados a Tumores/metabolismo , Antígeno Ca-125 , Ensaio de Imunoadsorção Enzimática , Biomarcadores Tumorais
12.
Wellcome Open Res ; 9: 20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434720

RESUMO

Background: Of over 8,000 recorded randomised trials addressing COVID-19, around 80% were of treatments, and 17% have reported results. Approximately 1% were adaptive or platform trials, with 25 having results available, across 29 journal articles and 10 preprint articles. Methods: We conducted an extensive literature review to address four questions about COVID-19 trials, particularly the role and impact of platform/adaptive trials and lessons learned. Results: The key findings were: Q1. Social value in conducting trials and uptake into policy? COVID-19 drug treatments varied substantially and changed considerably, with drugs found effective in definitive clinical trials replacing unproven drugs. Dexamethasone has likely saved ½-2 million lives, and was cost effective across a range of countries and populations, whereas the cost effectiveness of remdesivir is uncertain. Published economic and health system impacts of COVID-19 treatments were infrequent. Q2. Issues with adaptive trial designs. Of the 77 platform trials registered, 6 major platform trials, with approximately 50 treatment arms, recruited ~135,000 participants with funding over $100 million. Q3. Models of good practice. Streamlined set-up processes such as flexible and fast-track funding, ethics, and governance approvals are vital. To facilitate recruitment, simple and streamlined research processes, and pre-existing research networks to coordinate trial planning, design, conduct and practice change are crucial to success. Q4. Potential conflicts to avoid? When treating patients through trials, balancing individual and collective rights and allocating scarce resources between healthcare and research are challenging. Tensions occur between commercial and non-commercial sectors, and academic and public health interests, such as publication and funding driven indicators and the public good. Conclusion: There is a need to (i) reduce small, repetitive, single centre trials, (ii) increase coordination to ensure robust research conducted for treatments, and (iii) a wider adoption of adaptive/platform trial designs to respond to fast-evolving evidence landscape.

13.
Pediatr Obes ; 19(5): e13105, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38339799

RESUMO

INTRODUCTION: Whilst glucagon-like peptide-1 receptor agonists (GLP1-RAs) are effective for treating adolescent obesity, weight loss maintenance (WLM; preventing weight regain) remains a challenge. Our goal was to investigate appetite/satiety hormones and eating behaviours that may predict WLM with exenatide (a GLP1-RA) versus placebo in adolescents with severe obesity. METHODS: Adolescents who had ≥5% body mass index (BMI) reduction with meal replacement therapy were randomized to 52 weeks of once-weekly exenatide extended release or placebo. In this secondary analysis, eating behaviours and appetite/satiety regulation hormones post-meal replacement therapy (pre-randomization to exenatide or placebo) were evaluated as possible predictors of WLM. Percent change in BMI from randomization to 52 weeks served as the primary measure of WLM. RESULTS: The analysis included 66 adolescents (mean age 16.0 years; 47% female). Lower leptin response to meal testing was associated with greater WLM in terms of BMI percent change in those receiving exenatide compared to placebo (p = 0.007) after adjusting for sex, age and BMI. There were no other significant predictors of WLM. CONCLUSIONS: Prior to exenatide, lower leptin response to meals was associated with improved WLM with exenatide compared to placebo. The mostly null findings of this study suggest that GLP1-RA treatment may produce similar WLM for adolescents with obesity regardless of age, BMI, sex and eating behaviours.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Obesidade Infantil , Adolescente , Humanos , Feminino , Masculino , Obesidade Mórbida/tratamento farmacológico , Exenatida/uso terapêutico , Leptina , Apetite , Obesidade Infantil/tratamento farmacológico , Redução de Peso , Comportamento Alimentar , Hipoglicemiantes , Diabetes Mellitus Tipo 2/tratamento farmacológico
14.
Microbiol Resour Announc ; 13(3): e0093423, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38376340

RESUMO

Here, we report the draft genome sequences of Pseudomonas strains zfem001-005, five isolates from the intestinal microbiota of healthy larval zebrafish Danio rerio at a developmental age of 7 days post fertilization. The isolates have been identified as Pseudomonas sediminis, Pseudomonas japonica, Pseudomonas otitidis, Pseudomonas sichuanensis, and Pseudomonas tohonis, respectively.

15.
Br J Anaesth ; 132(5): 886-898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38336513

RESUMO

BACKGROUND: Digital health interventions offer a promising approach for monitoring during postoperative recovery. However, the effectiveness of these interventions remains poorly understood, particularly in children. The objective of this study was to assess the efficacy of digital health interventions for postoperative recovery in children. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with the use of automation tools for searching and screening. We searched five electronic databases for randomised controlled trials or non-randomised studies of interventions that utilised digital health interventions to monitor postoperative recovery in children. The study quality was assessed using Cochrane Collaboration's Risk of Bias tools. The systematic review protocol was prospectively registered with PROSPERO (CRD42022351492). RESULTS: The review included 16 studies involving 2728 participants from six countries. Tonsillectomy was the most common surgery and smartphone apps (WeChat) were the most commonly used digital health interventions. Digital health interventions resulted in significant improvements in parental knowledge about the child's condition and satisfaction regarding perioperative instructions (standard mean difference=2.16, 95% confidence interval 1.45-2.87; z=5.98, P<0.001; I2=88%). However, there was no significant effect on children's pain intensity (standard mean difference=0.09, 95% confidence interval -0.95 to 1.12; z=0.16, P=0.87; I2=98%). CONCLUSIONS: Digital health interventions hold promise for improving parental postoperative knowledge and satisfaction. However, more research is needed for child-centric interventions with validated outcome measures. Future work should focus development and testing of user-friendly digital apps and wearables to ease the healthcare burden and improve outcomes for children. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022351492).


Assuntos
Saúde Digital , Aplicativos Móveis , Humanos , Revisões Sistemáticas como Assunto
16.
Eur Heart J ; 45(12): 998-1013, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38243824

RESUMO

BACKGROUND AND AIMS: Knowledge of quantifiable cardiovascular disease (CVD) risk may improve health outcomes and trigger behavioural change in patients or clinicians. This review aimed to investigate the impact of CVD risk communication on patient-perceived CVD risk and changes in CVD risk factors. METHODS: PubMed, Embase, and PsycINFO databases were searched from inception to 6 June 2023, supplemented by citation analysis. Randomized trials that compared any CVD risk communication strategy versus usual care were included. Paired reviewers independently screened the identified records and extracted the data; disagreements were resolved by a third author. The primary outcome was the accuracy of risk perception. Secondary outcomes were clinician-reported changes in CVD risk, psychological responses, intention to modify lifestyle, and self-reported changes in risk factors and clinician prescribing of preventive medicines. RESULTS: Sixty-two trials were included. Accuracy of risk perception was higher among intervention participants (odds ratio = 2.31, 95% confidence interval = 1.63 to 3.27). A statistically significant improvement in overall CVD risk scores was found at 6-12 months (mean difference = -0.27, 95% confidence interval = -0.45 to -0.09). For primary prevention, risk communication significantly increased self-reported dietary modification (odds ratio = 1.50, 95% confidence interval = 1.21 to 1.86) with no increase in intention or actual changes in smoking cessation or physical activity. A significant impact on patients' intention to start preventive medication was found for primary and secondary prevention, with changes at follow-up for the primary prevention group. CONCLUSIONS: In this systematic review and meta-analysis, communicating CVD risk information, regardless of the method, reduced the overall risk factors and enhanced patients' self-perceived risk. Communication of CVD risk to patients should be considered in routine consultations.


Assuntos
Doenças Cardiovasculares , Abandono do Hábito de Fumar , Humanos , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Comunicação , Exercício Físico , Prevenção Primária/métodos
17.
Glomerular Dis ; 4(1): 19-32, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38293588

RESUMO

Introduction: More frequent and severe lupus nephritis (LN) has been reported in men compared to women, but data are limited and inconsistent. We conducted a meta-analysis of the literature to compare the histopathologic findings and outcomes between men and women with biopsy-proven LN. Methods: A systematic search of MEDLINE, Embase, Cochrane, and Web of Science databases was conducted through February 2021. Clinical information was extracted and synthesized from 25 studies that met inclusion criteria (1,210 men and 6,635 women). Pooled odds ratios (OR) with corresponding 95% confidence intervals (CIs) were generated via meta-analysis, and meta-regression was performed to assess the impact of several covariates, both using random-effects models. Results: Twenty studies reported kidney histopathology, eleven reported kidney outcomes, and eight reported mortality rates. Men had greater odds of class IV ± V LN (OR 1.26, 95% CI: 1.01-1.56), and the composite of end-stage kidney disease, persistent eGFR <15 mL/min or doubling of serum creatinine (OR 2.20, 95% CI: 1.59-3.06), and lower odds of complete remission (OR 0.52, 95% CI: 0.39-0.68). Mortality was not statistically significantly different between sexes (OR 1.50, 95% CI: 0.92-2.46). Meta-regression did not reveal statistically significant study-level relationships between sex differences in any of the covariates that could account for the greater odds of worse kidney outcome in males. Conclusion: Our analysis confirms the association between male sex and increased severity of LN as well as worse kidney outcomes. Larger prospective studies are needed to validate this association and inform treatment strategies adapted to this population.

18.
Int J Environ Health Res ; 34(1): 564-574, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36595614

RESUMO

The border city of El Paso, Texas, and its water utility, El Paso Water, initiated a SARS-CoV-2 wastewater monitoring program to assess virus trends and the appropriateness of a wastewater monitoring program for the community. Nearly weekly sample collection at four wastewater treatment facilities (WWTFs), serving distinct regions of the city, was analyzed for SARS-CoV-2 genes using the CDC 2019-Novel coronavirus Real-Time RT-PCR diagnostic panel. Virus concentrations ranged from 86.7 to 268,000 gc/L, varying across time and at each WWTF. The lag time between virus concentrations in wastewater and reported COVID-19 case rates (per 100,00 population) ranged from 4-24 days for the four WWTFs, with the strongest trend occurring from November 2021 - June 2022. This study is an assessment of the utility of a geographically refined SARS-CoV-2 wastewater monitoring program to supplement public health efforts that will manage the virus as it becomes endemic in El Paso.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Águas Residuárias , Texas/epidemiologia , Água
19.
Virus Res ; 339: 199272, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37981215

RESUMO

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) present significant healthcare challenges due to limited treatment options. Bacteriophage (phage) therapy offers potential as an alternative treatment. However, the high host specificity of phages poses challenges for their therapeutic application. To broaden the phage spectrum, laboratory-based phage training using the Appelmans protocol was employed in this study. As a result, the protocol successfully expanded the host range of a phage cocktail targeting CRAB. Further analysis revealed that the expanded host range phages isolated from the output cocktail were identified as recombinant derivatives originating from prophages induced from encountered bacterial strains. These findings provide valuable genetic insights into the protocol's mechanism when applied to phages infecting A. baumannii strains that have never been investigated before. However, it is noteworthy that the expanded host range phages obtained from this protocol exhibited limited stability, raising concerns about their suitability for therapeutic purposes.


Assuntos
Bacteriófagos , Prófagos , Prófagos/genética , Bacteriófagos/genética , Recombinação Genética , Especificidade de Hospedeiro
20.
J Med Internet Res ; 25: e49942, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37976100

RESUMO

BACKGROUND: Telehealth has been used for health care delivery for decades, but the COVID-19 pandemic greatly accelerated the uptake of telehealth in many care settings globally. However, few studies have carried out a direct comparison among different telehealth modalities, with very few studies having compared the effectiveness of telephone and video telehealth modalities. OBJECTIVE: This study aimed to identify and synthesize randomized controlled trials (RCTs) comparing synchronous telehealth consultations delivered by telephone and those conducted by video with outcomes such as clinical effectiveness, patient safety, cost-effectiveness, and patient and clinician satisfaction with care. METHODS: PubMed (MEDLINE), Embase, and CENTRAL were searched via the Cochrane Library from inception until February 10, 2023, for RCTs without any language restriction. Forward and backward citation searches were conducted on included RCTs. The Cochrane Risk of Bias 2 tool was used to assess the quality of the studies. We included studies carried out in any health setting-involving all types of outpatient cohorts and all types of health care providers-that compared synchronous video consultations directly with telephone consultations and reported outcomes specified in the objective. We excluded studies of clinician-to-clinician telehealth consults, hospitalized patients, and asynchronous consultations. RESULTS: Sixteen RCTs-10 in the United States, 3 in the United Kingdom, 2 in Canada, and 1 in Australia involving 1719 participants-were included in the qualitative and quantitative analyses. Most of the telehealth interventions were for hospital-based outpatient follow-ups, monitoring, and rehabilitation (n=13). The 3 studies that were conducted in the community all focused on smoking cessation. In half of the studies, nurses delivered the care (n=8). Almost all included studies had high or unclear risk of bias, mainly due to bias in the randomization process and selection of reported results. The trials found no substantial differences between telephone and video telehealth consultations with regard to clinical effectiveness, patient satisfaction, and health care use (cost-effectiveness) outcomes. None of the studies reported on patient safety or adverse events. We did not find any study on telehealth interventions for diagnosis, initiating new treatment, or those conducted in a primary care setting. CONCLUSIONS: Based on a small set of diverse trials, we found no notable differences between telephone and video consultations for the management of patients with an established diagnosis. There is also a significant lack of telehealth research in primary care settings despite its high uptake.


Assuntos
Telemedicina , Telefone , Humanos , Telemedicina/métodos , Satisfação Pessoal , Austrália , Canadá , Ensaios Clínicos Controlados Aleatórios como Assunto
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