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BACKGROUND: While previously considered a transient condition, with no lasting adverse impact, gestational diabetes mellitus (GDM) is now a well-established risk factor for developing type 2 diabetes mellitus (T2DM). The risk of developing T2DM appears to be particularly high in the first few years after childbirth, providing a compelling case for early intervention. This review provides an up-to-date systematic review and meta-analysis to assess the effectiveness of interventions to reduce incidence of T2DM in women with a recent history of GDM. METHODS: The search was conducted on October 20, 2023 with an annual surveillance planned for the next 5 years to maintain a living systematic review. The inclusion criteria were randomized controlled trials of any type in women within 5 years of GDM-complicated pregnancy that reported outcomes of T2DM diagnosis or measures of dysglycemia with a follow-up of at least 12 months. RESULTS: Seventeen studies met our inclusion criteria and have been included in this review. There were 3 pharmacological and 14 lifestyle interventions. Intervention was not associated with significant reduction in the primary outcome of T2DM (risk ratio, 0.78; 95% confidence interval [CI]: 0.43-1.41; p = 0.41; I2 = 79%) compared with the control group (placebo or usual care). However, meta-analysis of the four studies reporting hazard ratios suggested a reduction in diabetes incidence (hazard ratio, 0.68; 95% CI: 0.48-0.97; p = 0.03; I2 = 31%). CONCLUSION: This review provides equivocal evidence about the efficacy of interventions to reduce the risk of T2DM in women within 5 years of GDM-complicated pregnancy and highlights the need for further studies, including pharmacotherapy.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Humanos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/prevención & control , Embarazo , Femenino , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Factores de Riesgo , Hipoglucemiantes/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , IncidenciaRESUMEN
OBJECTIVE: Exposure to pesticides is a risk factor for various diseases, yet its association with biological aging remains unclear. We aimed to systematically investigate the relationship between pesticide exposure and biological aging. METHODS: PubMed, Embase and Web of Science were searched from inception to August 2023. Observational studies investigating the association between pesticide exposure and biomarkers of biological aging were included. Three-level random-effect meta-analysis was used to synthesize the data. Risk of bias was assessed by the Newcastle-Ottawa Scale. RESULTS: Twenty studies evaluating the associations between pesticide exposure and biomarkers of biological aging in 10,368 individuals were included. Sixteen reported telomere length and four reported epigenetic clocks. Meta-analysis showed no statistically significant associations between pesticide exposure and the Hannum clock (pooled ß = 0.27; 95â¯%CI: -0.25, 0.79), or telomere length (pooled Hedges'g = -0.46; 95â¯%CI: -1.10, 0.19). However, the opposite direction of effects for the two outcomes showed an indication of possible accelerated biological aging. After removal of influential effect sizes or low-quality studies, shorter telomere length was found in higher-exposed populations. CONCLUSION: The existing evidence for associations between pesticide exposure and biological aging is limited due to the scarcity of studies on epigenetic clocks and the substantial heterogeneity across studies on telomere length. High-quality studies incorporating more biomarkers of biological aging, focusing more on active chemical ingredients of pesticides and accounting for potential confounders are needed to enhance our understanding of the impact of pesticides on biological aging.
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Envejecimiento , Exposición a Riesgos Ambientales , Plaguicidas , Humanos , Envejecimiento/efectos de los fármacos , Biomarcadores , Exposición a Riesgos Ambientales/efectos adversos , Epigénesis Genética/efectos de los fármacos , Plaguicidas/toxicidad , Telómero/efectos de los fármacos , Homeostasis del Telómero/efectos de los fármacosRESUMEN
BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).
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Enfermedad Crítica , Mortalidad Hospitalaria , Hipoglucemia , Humanos , Enfermedad Crítica/mortalidad , Hipoglucemia/inducido químicamente , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Glucemia/análisis , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/sangre , Hiperglucemia/mortalidad , Control Glucémico/métodos , Adulto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Importance: There is uncertainty about whether prolonged infusions of ß-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective: To determine whether prolonged ß-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of ß-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of ß-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of ß-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged ß-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration: PROSPERO Identifier: CRD42023399434.
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Researchers incorporate health state utility values as inputs to inform economic models. However, for a particular health state or condition, multiple utility values derived from different studies typically exist and a single study is often insufficient to represent the best available source of utility needed to inform policy decisions. The purpose of this paper is to provide an introductory guidance for conducting Bayesian meta-analysis of health state utility values to generate a single parameter input for economic evaluation, using R. The tutorial is illustrated using data from a systematic review of health state utilities of patients with heart failure, with 21 studies that reported utilities measured using the EuroQol-5D (EQ-5D). Explanations, key considerations and suggested readings are provided for each step of the tutorial, adhering to a clear workflow for conducting Bayesian meta-analysis: (1) setting-up the data; (2) employing methods to impute missing standard deviations; (3) defining the priors; (4) fitting the model; (5) diagnosing model convergence; (6) interpreting the results; and (7) performing sensitivity analyses. The posterior distributions for the pooled effect size (i.e. mean health state utility) and between-study heterogeneity are discussed and interpreted in light of the data, priors and models used. We hope that this tutorial will foster interest in Bayesian methods and their applications in the meta-analysis of utilities.
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Teorema de Bayes , Estado de Salud , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/terapia , Modelos Económicos , Metaanálisis como Asunto , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Análisis Costo-BeneficioRESUMEN
CONTEXT: Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC. OBJECTIVE: To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments. EVIDENCE ACQUISITION: A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC. EVIDENCE SYNTHESIS: From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel. CONCLUSIONS: Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients. PATIENT SUMMARY: Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.
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BACKGROUND: The increasing number of studies that generate health state utility values (HSUVs) and the impact of HSUVs on cost-utility analyses make a robust tailored quality appraisal (QA) tool for systematic reviews of these studies necessary. OBJECTIVE: This study aimed to address conceptual issues regarding QA in systematic reviews of studies eliciting HSUVs by establishing a consensus on the definitions, dimensions and scope of a QA tool specific to this context. METHODS: A modified Delphi method was used in this study. An international multidisciplinary panel of seven experts was purposively assembled. The experts engaged in two anonymous online survey rounds. After each round, the experts received structured and controlled feedback on the previous phase. Controlled feedback allowed the experts to re-evaluate and adjust their positions based on collective insights. Following these surveys, a virtual face-to-face meeting was held to resolve outstanding issues. Consensus was defined a priori at all stages of the modified Delphi process. RESULTS: The response rates to the first-round and second-round questionnaires and the virtual consensus meeting were 100%, 86% and 71%, respectively. The entire process culminated in a consensus on the definitions of scientific quality, QA, the three QA dimensions-reporting, relevance and methodological quality-and the scope of a QA tool specific to studies that elicit HSUVs. CONCLUSIONS: Achieving this consensus marks a pivotal step towards developing a QA tool specific to systematic reviews of studies eliciting HSUVs. Future research will build on this foundation, identify QA items, signalling questions and response options, and develop a QA tool specific to studies eliciting HSUVs.
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Análisis Costo-Beneficio , Técnica Delphi , Humanos , Estado de Salud , Encuestas y Cuestionarios , Consenso , Literatura de Revisión como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: The SSaSS (Salt Substitute and Stroke Study) has shown that use of a potassium-enriched salt lowers the risk of stroke, total cardiovascular events, and premature death. The effects on cause-specific cardiac outcomes are reported here. METHODS: SSaSS was an unblinded, cluster-randomised trial assessing the effects of potassium-enriched salt compared with regular salt among 20 995 Chinese adults with established stroke and older age and uncontrolled hypertension. Post hoc efficacy analyses were performed using an intention-to-treat method and a hierarchical Poisson regression model adjusting for clustering to obtain rate ratios and 95% CIs. We assessed acute coronary syndrome, heart failure, arrhythmia, and sudden death. RESULTS: Over a mean 4.74 years follow-up, there were 695 acute coronary syndrome events, 454 heart failure events, 230 arrhythmia events, and 1133 sudden deaths recorded. The rates of events were lower in potassium-enriched salt group for all outcomes but CIs were wide for most: acute coronary syndrome (6.32 versus 7.65 events per 1000 person-years; rate ratio, 0.80 [95% CI, 0.65-0.99]); heart failure (9.14 versus 11.32 events per 1000 person-years; rate ratio, 0.88 [95% CI, 0.60-1.28]); arrhythmia (4.43 versus 6.20 events per 1000 person-years; rate ratio, 0.59 [95% CI, 0.35-0.98]); and sudden death (11.01 versus 11.76 events per 1000 person-years; rate ratio, 0.94 [95% CI, 0.82-1.07]; all P>0.05 with adjustment for multiple comparisons). CONCLUSIONS: These results suggest that use of potassium-enriched salt is more likely to prevent than cause cardiac disease but the post hoc nature of these analyses precludes definitive conclusions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02092090.
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Síndrome Coronario Agudo , Insuficiencia Cardíaca , Accidente Cerebrovascular , Adulto , Humanos , Arritmias Cardíacas , Muerte Súbita , Potasio , Accidente Cerebrovascular/prevención & controlRESUMEN
Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.
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Hipertensión , Indapamida , Humanos , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Indapamida/farmacología , Indapamida/uso terapéutico , Presión Sanguínea , Resultado del TratamientoRESUMEN
BACKGROUND: Headache is one of the most common neurological symptoms. Headache disorders are associated with a high global burden of disease. Prior studies indicate that short-to-medium term sodium reduction reduces headache symptom. This study evaluated the effects of long-term reduced-sodium, added-potassium salt on headache frequency and severity in rural China. METHODS: The Salt substitute and stroke study (SSaSS) was an open-label cluster-randomised trial in rural China designed to evaluate the effect of salt substitution on mortality and cardiovascular events. Participants included adults with a history of prior stroke and those aged ≥60 years with uncontrolled high blood pressure (BP). Villages were randomly assigned in a 1:1 ratio either to intervention with salt substitute (75% sodium chloride and 25% potassium chloride by mass) or to control with continued use of regular salt (100% sodium chloride). In this pre-specified analysis, between-group differences in headache frequency and severity were evaluated. The study was registered with ClinicalTrials.gov (identifier number: NCT02092090). RESULTS: A total of 20,995 participants were included in the trial (mean age 64.3 years, 51% female, mean follow-up 4.7 years). At final follow-up at the end of the study, headache outcome data including frequency and severity of headaches was available for 16,486 (98%) of 16,823 living participants. Overall, 4454/16,486 (27%) individuals reported having headache: 27.4% in the intervention group (2301/8386) vs 26.6% in the control group (2153/8100) (RR 1.04, 95% CI: 0.93, 1.16, p = 0.48). There was no difference in headache severity between intervention and control groups (p = 0.90). CONCLUSION: Long term salt substitution did not reduce the frequency or severity of headaches in this population.
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Cefalea , Cloruro de Sodio Dietético , Humanos , Femenino , Masculino , Persona de Mediana Edad , China/epidemiología , Cloruro de Sodio Dietético/administración & dosificación , Anciano , Índice de Severidad de la Enfermedad , Dieta Hiposódica/métodosRESUMEN
OBJECTIVE: The overarching aim of this scoping review is to describe and analyze the scope of use and reporting of Bayesian methods in meta-analyses in biomedical research. INTRODUCTION: The Bayesian approach provides a powerful and flexible framework for meta-analysis, particularly suited for dealing with complex, sparse, or heterogeneous data. Due to these advantages and its appeal, Bayesian methods have been increasingly used in many areas of biomedical research; however, their use in meta-analysis remains scarce. INCLUSION CRITERIA: This review will include studies that used Bayesian methods for meta-analysis of primary studies in biomedical research. METHODS: The proposed review will be conducted in accordance with the JBI methodology for scoping reviews. PubMed, Embase, CINAHL, and the Cochrane Database of Systematic Reviews will be searched to identify relevant full-text papers published since 2016 in English. No geographical restriction will be applied. Two reviewers will screen the articles and extract the data using a tool that will be pilot-tested and revised, as necessary. Analysis will involve frequency counts, narrative synthesis, and mapping concepts to propose an appropriate workflow. The details of the scoping review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guideline. REVIEW REGISTRATION: Open Science Framework https://osf.io/jenp4/.
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Investigación Biomédica , Humanos , Teorema de Bayes , Bases de Datos Factuales , Revisiones Sistemáticas como Asunto , Literatura de Revisión como Asunto , Metaanálisis como AsuntoRESUMEN
BACKGROUND: The effects of seasonal influenza vaccination on cardiovascular disease (CVD) outcomes, including among individuals with established CVD, are uncertain. METHODS: To evaluate the efficacy and safety of influenza vaccines compared to no vaccines or placebo for preventing all-cause/CVD mortality or all-cause/CVD hospitalization in the general population and in populations with pre-existing CVD, we conducted a living systematic review (LSR) and prospective meta-analysis (PMA). Published randomized controlled trials (RCT) and observational studies between 1994 and 2023 were searched. PRISMA guidelines were followed in the extraction of study details, and risk of bias was assessed using the Cochrane tools. Analyses were stratified by study design and CVD history. Study quality was evaluated using GRADE system. Meta analyses based on random-effects models were performed between July and October 2022. Pooled risk ratios (RRs) for all-cause/CVD mortality and all-cause/CVD hospitalization were main outcomes. RESULTS: Six published RCTs comprising 12,662 participants (mean age, 62 years; 45 % women; 8,797 with pre-existing CVD) and 37 observational studies comprising 6,311,703 participants (mean age, 49 years; 50 % women; 1,189,955 with pre-existing CVD) were included. Only those RCTs judged to be low risk were included in the analyses, and observational studies at anything greater than moderate risk of bias were excluded. In RCTs, influenza vaccine was not significantly associated with lower all-cause mortality (RR, 0.85; 95 %CI, 0.61-1.17), cardiovascular death (RR, 0.80; 95 %CI, 0.60-1.07), or CVD hospitalization (RR, 0.69; 95 %CI, 0.47-1.02). A statistically significant reduction in all-cause hospitalization (RR, 0.86; 95 %CI, 0.76-0.97) was observed. The evidence level was assessed as moderate for all-cause hospitalization, and low for other outcomes. Overall, observational studies suggested a stronger protective association between influenza vaccination and outcomes, except for CVD hospitalization. Based on RCTs, there was no difference in the effects of influenza vaccination on all-cause mortality among the general population compared to those with pre-existing CVD, although the summary point estimate favored benefits only in those with pre-existing CVD. CONCLUSIONS: While observational studies suggest that influenza vaccination may be associated with lower all-cause and CVD mortality and all-cause hospitalization, RCTs reported to date suggest a reduction in the risk of all-cause hospitalization but do not provide clear evidence to support preventive effects on mortality (all-cause or CVD) or CVD hospitalization.
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Enfermedades Cardiovasculares , Hospitalización , Vacunas contra la Influenza , Gripe Humana , Vacunación , Humanos , Vacunas contra la Influenza/administración & dosificación , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Hospitalización/estadística & datos numéricos , Gripe Humana/prevención & control , Gripe Humana/mortalidad , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Persona de Mediana Edad , Femenino , MasculinoRESUMEN
BACKGROUND: As new therapeutic options become available, better understanding the potential impact of emerging therapies on clinical outcomes of hepatits D virus (HDV) is critical. OBJECTIVE: The aim of this study was to develop a natural history model for patients with hepatitis D virus. METHODS: We developed a model (decision tree followed by a Markov cohort model) in adults with chronic HDV infection to assess the natural history and impact of novel treatments on disease progression versus best supportive care (BSC). The model time horizon was over a lifetime (up to 100 years of age); state transitions and health states were defined by responder status. Patients in fibrosis stages 0 through 4 received treatment; decompensated patients were not treated. Response was defined as the combined response endpoint of achievement of HDV-RNA undetectability/≥2-log10 decline and alanine aminotransferase normalization; response rates of 50% and 75% were explored. Health events associated with advanced liver disease were modeled as the number of events per 10,000 patients. Scenario analyses of early treatment, alternate treatment response, and no fibrosis regression for treatment responders were also explored. RESULTS: The model was able to reflect disease progression similarly to published natural history studies for patients with HBV/HDV infection. In a hypothetical cohort of patients reflecting a population enrolled in a recent clinical trial, fewer advanced liver disease events were observed with a novel HDV treatment versus BSC. Fewer liver-related deaths were observed under 50% and 75% response (900 and 1,358 fewer deaths, respectively, per 10,000 patients). Scenario analyses showed consistently fewer advanced liver disease events with HDV treatment compared with BSC, with greater reductions observed with earlier treatment. CONCLUSION: This HDV disease progression model replicated findings from natural history studies. Furthermore, it found that a hypothetical HDV treatment results in better clinical outcomes for patients versus BSC, with greater benefit observed when starting treatment early. This validated natural history model for HBV/HDV infection can serve as a foundation for future clinical and economic analyses of novel HDV treatments that can support healthcare stakeholders in the management of patients with chronic HDV.
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BACKGROUND AND AIMS: Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive. APPROACH AND RESULTS: A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)]. CONCLUSIONS: The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Virus de la Hepatitis Delta/genética , Antígenos de Superficie de la Hepatitis B , Cirrosis Hepática/complicaciones , Morbilidad , ARN Viral , Progresión de la Enfermedad , Virus de la Hepatitis B/genéticaRESUMEN
BACKGROUND: The effect of balanced crystalloids compared with that of saline in critically ill patients overall and in specific subgroups is unclear. We aimed to assess whether use of balanced solutions, compared with 0·9% sodium chloride (saline), decreased in-hospital mortality in adult patients in intensive care units (ICUs). METHODS: For this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, and CENTRAL databases from inception until March 1, 2022 (updated Sept 1, 2023) for individually randomised and cluster-randomised trials comparing balanced solutions with saline for adult patients in the ICU. Eligible trials were those that allocated patients to receive balanced solutions or saline for fluid resuscitation and maintenance fluids, or for maintenance fluids only; and administered the allocated fluid throughout ICU admission or, for trials using landmark mortality as their primary outcome, until the timepoint at which mortality was assessed (if ≥28 days). Authors of eligible trials were contacted to request individual patient data. Data obtained from eligible trials were merged, checked for accuracy, and centrally analysed by use of Bayesian regression models. The primary outcome was in-hospital mortality. Prespecified subgroups included patients with traumatic brain injury. This study was registered with PROSPERO (CRD42022299282). FINDINGS: Our search identified 5219 records, yielding six eligible randomised controlled trials. Data obtained for 34 685 participants from the six trials, 17 407 assigned to receive balanced crystalloids and 17 278 to receive saline, were included in the analysis. The mean age of participants was 58·8 years (SD 17·5). Of 34 653 participants with available data, 14 579 (42·1%) were female and 20 074 (57·9%) were male. Among patients who provided consent to report in-hospital mortality, 2907 (16·8%) of 17 313 assigned balanced solutions and 2975 (17·3%) of 17 166 assigned saline died in hospital (odds ratio [OR] 0·962 [95% CrI 0·909 to 1·019], absolute difference -0·4 percentage points [-1·5 to 0·2]). The posterior probability that balanced solutions reduced mortality was 0·895. In patients with traumatic brain injury, 191 (19·1%) of 999 assigned balanced and 141 (14·7%) of 962 assigned saline died (OR 1·424 [1·100 to 1·818], absolute difference 3·2 percentage points [0·7 to 8·7]). The probability that balanced solutions increased mortality in patients with traumatic brain injury was 0·975. In an independent risk of bias assessment, two trials were deemed to be at low risk of bias and four at high risk of bias. INTERPRETATION: The probability that using balanced solutions in the ICU reduces in-hospital mortality is high, although the certainty of the evidence was moderate and the absolute risk reduction was small. In patients with traumatic brain injury, using balanced solutions was associated with increased in-hospital mortality. FUNDING: HCor (Brazil) and The George Institute for Global Health (Australia).
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Lesiones Traumáticas del Encéfalo , Enfermedad Crítica , Soluciones Cristaloides , Solución Salina , Humanos , Persona de Mediana Edad , Teorema de Bayes , Lesiones Traumáticas del Encéfalo/terapia , Enfermedad Crítica/terapia , Soluciones Cristaloides/uso terapéutico , Solución Salina/uso terapéuticoRESUMEN
ABSTRACT: Purpose: To examine the relationship of early persistent lymphopenia with hospital survival in critically ill patients with and without sepsis to assess whether it can be considered a treatable trait. Methods: Retrospective database analysis of patients with nonelective admission to intensive care units (ICUs) during January 2015 to December 2018. Patients were classified as having sepsis if the Acute Physiology and Chronic Health Evaluation III admission diagnostic code included sepsis or coded for an infection combined with a Sequential Organ Failure Assessment score of ≥2. We defined early persistent lymphopenia at two thresholds (absolute lymphocyte count [ALC] <1.0 and <0.75 × 10 9 /L) based on two qualifying values recorded during the first 4 days in ICU. The main outcome measure was time to in-hospital death. Results: Of 8,507 eligible patients, 7,605 (89.4%) had two ALCs recorded during their first 4 days in ICU; of these, 1,482 (19.5%) had sepsis. Persistent lymphopenia (ALC <1.0) was present in 728 of 1,482 (49.1%) and 2,302 of 6,123 (37.6%) patients with and without sepsis, respectively. For ALC <0.75, the results were 487 of 1,482 (32.9%) and 1,125 of 6,123 (18.4%), respectively. Of 3,030 patients with persistent lymphopenia (ALC <1.0), 562 (18.5%) died compared with 439 of 4,575 (9.6%) without persistent lymphopenia. Persistent lymphopenia was an independent risk factor for in-hospital death in all patients. The hazard ratios for death at ALC <1.0 were 1.89 (95% confidence interval, 1.32-2.71; P = 0.0005) and 1.17 (95% confidence interval, 1.02-1.35; P = 0.0246) in patients with and without sepsis respectively. Conclusions: Early persistent lymphopenia is common in critically ill patients and associated with increased risk of death in patients with and without sepsis. Although the association is stronger in patients with sepsis, lymphopenia is a candidate to be considered a treatable trait; drugs that reverse lymphopenia should be trialed in critically ill patients.
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Linfopenia , Sepsis , Humanos , Estudios Retrospectivos , Enfermedad Crítica , Mortalidad Hospitalaria , Pronóstico , Linfopenia/complicaciones , Unidades de Cuidados Intensivos , Curva ROCRESUMEN
BACKGROUND: This review is an update of a rapid review undertaken in 2020 to identify relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control. The rapid review was published when little was known about transmission, treatment or future vaccination, and when physical distancing measures (isolation, quarantine, contact tracing, crowd avoidance, work and school measures) were the cornerstone of public health responses globally. This updated review includes more recent evidence to extend what we know about effective pandemic public health communication. This includes considerations of changes needed over time to maintain responsiveness to pandemic transmission waves, the (in)equities and variable needs of groups within communities due to the pandemic, and highlights again the critical role of effective communication as integral to the public health response. OBJECTIVES: To update the evidence on the question 'What are relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control?', our primary focus was communication approaches to promote and support acceptance, uptake and adherence to physical distancing. SECONDARY OBJECTIVE: to explore and identify key elements of effective communication for physical distancing measures for different (diverse) populations and groups. SEARCH METHODS: We searched MEDLINE, Embase and Cochrane Library databases from inception, with searches for this update including the period 1 January 2020 to 18 August 2021. Systematic review and study repositories and grey literature sources were searched in August 2021 and guidelines identified for the eCOVID19 Recommendations Map were screened (November 2021). SELECTION CRITERIA: Guidelines or reviews focusing on communication (information, education, reminders, facilitating decision-making, skills acquisition, supporting behaviour change, support, involvement in decision-making) related to physical distancing measures for prevention and/or control of COVID-19 or selected other diseases (sudden acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, Ebola virus disease (EVD) or tuberculosis (TB)) were included. New evidence was added to guidelines, reviews and primary studies included in the 2020 review. DATA COLLECTION AND ANALYSIS: Methods were based on the original rapid review, using methods developed by McMaster University and informed by Cochrane rapid review guidance. Screening, data extraction, quality assessment and synthesis were conducted by one author and checked by a second author. Synthesis of results was conducted using modified framework analysis, with themes from the original review used as an initial framework. MAIN RESULTS: This review update includes 68 studies, with 17 guidelines and 20 reviews added to the original 31 studies. Synthesis identified six major themes, which can be used to inform policy and decision-making related to planning and implementing communication about a public health emergency and measures to protect the community. Theme 1: Strengthening public trust and countering misinformation: essential foundations for effective public health communication Recognising the key role of public trust is essential. Working to build and maintain trust over time underpins the success of public health communications and, therefore, the effectiveness of public health prevention measures. Theme 2: Two-way communication: involving communities to improve the dissemination, accessibility and acceptability of information Two-way communication (engagement) with the public is needed over the course of a public health emergency: at first, recognition of a health threat (despite uncertainties), and regularly as public health measures are introduced or adjusted. Engagement needs to be embedded at all stages of the response and inform tailoring of communications and implementation of public health measures over time. Theme 3: Development of and preparation for public communication: target audience, equity and tailoring Communication and information must be tailored to reach all groups within populations, and explicitly consider existing inequities and the needs of disadvantaged groups, including those who are underserved, vulnerable, from diverse cultural or language groups, or who have lower educational attainment. Awareness that implementing public health measures may magnify existing or emerging inequities is also needed in response planning, enactment and adjustment over time. Theme 4: Public communication features: content, timing and duration, delivery Public communication needs to be based on clear, consistent, actionable and timely (up-to-date) information about preventive measures, including the benefits (whether for individual, social groupings or wider society), harms (likewise) and rationale for use, and include information about supports available to help follow recommended measures. Communication needs to occur through multiple channels and/or formats to build public trust and reach more of the community. Theme 5: Supporting behaviour change at individual and population levels Supporting implementation of public health measures with practical supports and services (e.g. essential supplies, financial support) is critical. Information about available supports must be widely disseminated and well understood. Supports and communication related to them require flexibility and tailoring to explicitly consider community needs, including those of vulnerable groups. Proactively monitoring and countering stigma related to preventive measures (e.g. quarantine) is also necessary to support adherence. Theme 6: Fostering and sustaining receptiveness and responsiveness to public health communication Efforts to foster and sustain public receptiveness and responsiveness to public health communication are needed throughout a public health emergency. Trust, acceptance and behaviours change over time, and communication needs to be adaptive and responsive to these changing needs. Ongoing community engagement efforts should inform communication and public health response measures. AUTHORS' CONCLUSIONS: Implications for practice Evidence highlights the critical role of communication throughout a public health emergency. Like any intervention, communication can be done well or poorly, but the consequences of poor communication during a pandemic may mean the difference between life and death. The approaches to effective communication identified in this review can be used by policymakers and decision-makers, working closely with communication teams, to plan, implement and adjust public communications over the course of a public health emergency like the COVID-19 pandemic. Implications for research Despite massive growth in research during the COVID-19 period, gaps in the evidence persist and require high-quality, meaningful research. This includes investigating the experiences of people at heightened COVID-19 risk, and identifying barriers to implementing public communication and protective health measures particular to lower- and middle-income countries, and how to overcome these.
Asunto(s)
COVID-19 , Humanos , COVID-19/prevención & control , Pandemias/prevención & control , Distanciamiento Físico , Salud Pública , ComunicaciónRESUMEN
OBJECTIVES: Compare two approaches to analyzing time series data-interrupted time series with segmented regression (ITS-SR) and Bayesian structural time series using the CausalImpact R package (BSTS-CI)-highlighting advantages, disadvantages, and implementation considerations. STUDY DESIGN AND SETTING: We analyzed electronic health records using each approach to estimate the antibiotic prescribing reduction associated with an educational program delivered to Australian primary care physicians between 2012 and 2017. Two outcomes were considered: antibiotics for upper respiratory tract infections (URTIs) and antibiotics of specified formulations. RESULTS: For URTI indication prescribing, average monthly prescriptions changes were estimated at -4,550; (95% confidence interval, -5,486 to -3,614) and -4,270; (95% credible interval, -5,934 to -2,626) for ITS-SR and BSTS-CI, respectively. Similarly for specified formulation prescribing, monthly average changes were estimated at -7,923; (95% confidence interval, -15,887 to 40) for ITS-SR and -20,269; (95% credible interval, -25,011 to -15,635) for BSTS-CI. CONCLUSION: Differing results between ITS-SR and BSTS-CI appear driven by divergent explanatory and outcome series trends. The BSTS-CI may be a suitable alternative to ITS-SR only if the explanatory series represent the secular trend of the outcome series before the intervention and are equally affected by exogenous or confounding factors. When appropriately applied, BSTS-CI provides an alternative to ITS with more readily interpretable Bayesian effect estimates.