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Insomnia is a highly prevalent sleep disorder. It is the most frequent sleep complaint among Higher Education students. The Sleep Condition Indicator is a self-report tool aimed at assessing insomnia based on the DSM-5 criteria. The principal goal of this study was to establish preliminary psychometric properties of the European Portuguese version of the Sleep Condition Indicator in a sample of Higher Education students. Data from a diverse pool of Higher Education students (N = 537) were collected online over a month. Most participants were women (75%) and aged approximately 27 years. The Sleep Condition Indicator demonstrated good internal consistency (α = 0.85), with all the items accounting significantly for the scale reliability. The most appropriate factor structure considering the ordinal nature of the items was unidimensional, with all items explaining 64% of the total variance. However, a two-factor structure (sleep pattern and sleep-related impact) was also plausible when other statistical estimators were used. The Sleep Condition Indicator correlated significantly with insomnia severity, vulnerability to stress-related sleep disturbance, and self-reported daytime sleepiness. The optimal cut-off point established based on the receiver operating characteristic curve analysis was ≤ 16. A short version comprising only two items was also viable as suggested by the literature. The Sleep Condition Indicator is a reliable and valid tool for screening for insomnia. More studies with other groups are now required, specifically with clinical samples.
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We respond to discussant comments on our paper "Twenty years of network meta-analysis: Continuing controversies and recent developments" (https://doi.org/10.1002/jrsm.1700) and raise some additional points for consideration, including: the way in which methodological guidance is generated; integration of the estimand framework with evidence synthesis; and implications of the European Joint Clinical Assessment. We ask: what properties are required of population adjustment methods to enable transparent and consistent decision-making? We also ask why individual patient data is not routinely made available to re-imbursement authorities and clinical guideline developers.
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Residential care facilities (RCFs) are places where older people live and usually die. This exploratory qualitative study aims to describe the experiences and practices of the directors of Portuguese RCFs regarding residents' end of life and death. Data were obtained from 17 care facility directors (CFDs) who participated in three focus groups. Thematic data analysis was performed. The CFDs described their practices and experiences framed within three moments in the life journey of the residents in RCFs: admission and living in RCF; end of life and death; postmortem and new admission - continuing and occupying the vacancy. The results suggest that end of life and death are only addressed in the last days/hours of life of the resident. However, the CFDs' approach throughout the stay of the residents in the RCF could allow for the expression of their wishes and wills, which could facilitate a good and dignified death.
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While various treatment options for primary snoring are available, evidence-based recommendations to determine the optimal intervention remain unestablished. To inform future directions of research to guide clinical decision-making, this scoping review was conducted to map the existing evidence on interventions for primary snoring, the outcomes and instruments used to assess their clinical effects in adults. The feasibility of conducting further systematic reviews and comparing outcomes across these therapies using network meta-analysis was also assessed. Of the 1673 records identified, 38 interventional studies met the inclusion criteria with three-fifths of them being before-after studies. The most common reason for study exclusion was results being reported for patients with primary snoring and obstructive sleep apnoea (OSA) combined. Interventions were surgical (73 %), behavioural and the use of devices/medications. Twenty-six common outcomes were identified and categorised into six domains. Fifty-nine instruments were used to assess the outcomes and based mainly on non-validated questionnaires. Our findings indicated (1) the need for randomised controlled trials with strict discrimination between patients with primary snoring and OSA, (2) further network meta-analyses using some outcomes is feasible, and (3) a core outcome set to inform standardised reporting for future research should be developed.
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Objectives: To assess whether age, sex, comorbidity count, and race and ethnic group are associated with the likelihood of trial participants not being enrolled in a trial for any reason (ie, screen failure). Design: Bayesian meta-analysis of individual participant level data. Setting: Industry funded phase 3/4 trials of chronic medical conditions. Participants: Participants were identified using individual participant level data to be in either the enrolled group or screen failure group. Data were available for 52 trials involving 72 178 screened individuals of whom 24 733 (34%) were excluded from the trial at the screening stage. Main outcome measures: For each trial, logistic regression models were constructed to assess likelihood of screen failure in people who had been invited to screening, and were regressed on age (per 10 year increment), sex (male v female), comorbidity count (per one additional comorbidity), and race or ethnic group. Trial level analyses were combined in Bayesian hierarchical models with pooling across condition. Results: In age and sex adjusted models across all trials, neither age nor sex was associated with increased odds of screen failure, although weak associations were detected after additionally adjusting for comorbidity (odds ratio of age, per 10 year increment was 1.02 (95% credibility interval 1.01 to 1.04) and male sex (0.95 (0.91 to 1.00)). Comorbidity count was weakly associated with screen failure, but in an unexpected direction (0.97 per additional comorbidity (0.94 to 1.00), adjusted for age and sex). People who self-reported as black seemed to be slightly more likely to fail screening than people reporting as white (1.04 (0.99 to 1.09)); a weak effect that seemed to persist after adjustment for age, sex, and comorbidity count (1.05 (0.98 to 1.12)). The between-trial heterogeneity was generally low, evidence of heterogeneity by sex was noted across conditions (variation in odds ratios on log scale of 0.01-0.13). Conclusions: Although the conclusions are limited by uncertainty about the completeness or accuracy of data collection among participants who were not randomised, we identified mostly weak associations with an increased likelihood of screen failure for age, sex, comorbidity count, and black race or ethnic group. Proportionate increases in screening these underserved populations may improve representation in trials. Trial registration number: PROSPERO CRD42018048202.
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OBJECTIVES: This study aimed to evaluate the cost-effectiveness of anti-vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. METHODS: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. RESULTS: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of £3688, with a net health benefit of -0.214 at a £20 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. CONCLUSIONS: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties.
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Inhibidores de la Angiogénesis , Análisis Costo-Beneficio , Retinopatía Diabética , Años de Vida Ajustados por Calidad de Vida , Factor A de Crecimiento Endotelial Vascular , Humanos , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/economía , Retinopatía Diabética/terapia , Retinopatía Diabética/cirugía , Inhibidores de la Angiogénesis/economía , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Reino Unido , Agudeza Visual , Fotocoagulación/economía , Fotocoagulación/métodos , Modelos Económicos , Persona de Mediana Edad , Resultado del Tratamiento , Coagulación con Láser/economía , Coagulación con Láser/métodos , Masculino , Femenino , Edema Macular/tratamiento farmacológico , Edema Macular/economía , Edema Macular/terapia , Análisis de Costo-EfectividadRESUMEN
OBJECTIVE: To analyze the clinical and physiological outcomes of NIV-NAVA in preterm infants compared with other non-invasive respiratory support. STUDY DESIGN: We conducted a meta-analysis of RCTs and randomized crossover studies comparing NIV-NAVA to other non-invasive strategies in preterm neonates. RESULTS: NIV-NAVA was superior to other non-invasive support in maximum EAdi (MD - 0.66 µV; 95% CI - 1.17 to -0.15; p = 0.01), asynchrony index (MD - 49.8%; 95% CI - 63.1 to -36.5; p < 0.01), and peak inspiratory pressure (MD - 2.2 cmH2O; 95% CI - 2.7 to -1.7; p < 0.01). However, there were no significant differences in the incidences of intubation (RR 0.91; 95% CI 0.56-1.48; p = 0.71), reintubation (RR 0.72; 95% CI 0.45-1.16; p = 0.18), or bronchopulmonary dysplasia (RR 0.77; 95% CI 0.37-1.60; p = 0.48). CONCLUSION: NIV-NAVA was associated with improvements in maximum Edi, asynchrony index, and peak inspiratory pressure relative to other non-invasive respiratory strategies, without significant differences in clinical outcomes between groups.
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Network meta-analysis (NMA) is an extension of pairwise meta-analysis (PMA) which combines evidence from trials on multiple treatments in connected networks. NMA delivers internally consistent estimates of relative treatment efficacy, needed for rational decision making. Over its first 20 years NMA's use has grown exponentially, with applications in both health technology assessment (HTA), primarily re-imbursement decisions and clinical guideline development, and clinical research publications. This has been a period of transition in meta-analysis, first from its roots in educational and social psychology, where large heterogeneous datasets could be explored to find effect modifiers, to smaller pairwise meta-analyses in clinical medicine on average with less than six studies. This has been followed by narrowly-focused estimation of the effects of specific treatments at specific doses in specific populations in sparse networks, where direct comparisons are unavailable or informed by only one or two studies. NMA is a powerful and well-established technique but, in spite of the exponential increase in applications, doubts about the reliability and validity of NMA persist. Here we outline the continuing controversies, and review some recent developments. We suggest that heterogeneity should be minimized, as it poses a threat to the reliability of NMA which has not been fully appreciated, perhaps because it has not been seen as a problem in PMA. More research is needed on the extent of heterogeneity and inconsistency in datasets used for decision making, on formal methods for making recommendations based on NMA, and on the further development of multi-level network meta-regression.
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INTRODUCTION: Network meta-analyses (NMAs) have gained popularity and grown in number due to their ability to provide estimates of the comparative effectiveness of multiple treatments for the same condition. The aim of this study is to conduct a methodological review to compile a preliminary list of concepts related to bias in NMAs. METHODS AND ANALYSIS: We included papers that present items related to bias, reporting or methodological quality, papers assessing the quality of NMAs, or method papers. We searched MEDLINE, the Cochrane Library and unpublished literature (up to July 2020). We extracted items related to bias in NMAs. An item was excluded if it related to general systematic review quality or bias and was included in currently available tools such as ROBIS or AMSTAR 2. We reworded items, typically structured as questions, into concepts (i.e. general notions). RESULTS: One hundred eighty-one articles were assessed in full text and 58 were included. Of these articles, 12 were tools, checklists or journal standards; 13 were guidance documents for NMAs; 27 were studies related to bias or NMA methods; and 6 were papers assessing the quality of NMAs. These studies yielded 99 items of which the majority related to general systematic review quality and biases and were therefore excluded. The 22 items we included were reworded into concepts specific to bias in NMAs. CONCLUSIONS: A list of 22 concepts was included. This list is not intended to be used to assess biases in NMAs, but to inform the development of items to be included in our tool.
HIGHLIGHTS: ⢠Our research aimed to develop a preliminary list of concepts related to bias with the goal of developing the first tool for assessing the risk of bias in the results and conclusions of a network meta-analysis (NMA).⢠We followed the methodology proposed by Whiting (2017) and Sanderson (2007) for creating systematically developed lists of quality items, as a first step in the development of a risk of bias tool for network meta-analysis (RoB NMA Tool).⢠We included items related to biases in NMAs and excluded items that are equally applicable to all systematic reviews as they are covered by other tools (e.g. ROBIS, AMSTAR 2).⢠Fifty-seven studies were included generating 99 items, which when screened, yielded 22 included items. These items were then reworded into concepts in preparation for a Delphi process for further vetting by external experts.⢠A limitation of our study is the challenge in retrieving methods studies as methods collections are not regularly updated.
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Lista de Verificación , Humanos , Sesgo , Metaanálisis en RedRESUMEN
OBJECTIVES: To explore the impact of using different data standardization and scale-specific re-expression methods (i.e., processes to convert standardized data into scale-specific units) in meta-analyses using standardized mean differences (SMDs). STUDY DESIGN AND SETTING: We used data assessed by the Short Physical Performance Battery and the Barthel Index from a meta-analysis of randomized controlled trials which synthesized evidence of physical activity effectiveness on the functional capacity of hospitalized older adults. We standardized the data using study-specific pooled standard deviations (SDs), an internal, and an external SD references. Bayesian meta-analyses were performed for each method to compare the posterior distributions of the meta-analysis parameters. Posterior estimates were re-expressed into scale-specific units applying different methods established in the Cochrane guidelines. RESULTS: Meta-analysis estimates depend on the used standardization method. Analyses including data standardized using the largest SD reference presented lower estimates with less uncertainty in both scales. The method applied for re-expressing SMDs into scale-specific units impacted in their posterior clinical interpretation. The most similar results across models were obtained when using the same SD reference to standardize and re-express data. CONCLUSION: Different data standardization methods yielded different meta-analysis estimates on the SMD scale. To avoid the introduction of bias, the use of a single scale-specific SD reference to standardize data is recommended and instead of study-specific pooled sample SDs. Meta-analysis software packages may therefore change their default methods to allow this method by a single scale-specific SD. To re-express the SMDs into scale-specific units, we suggest the application of the same SD reference that was used for data standardization.
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Ejercicio Físico , Humanos , Anciano , Teorema de Bayes , SesgoRESUMEN
Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder mainly affecting children. ADHD children brain activity is reported to present alterations from neurotypically developed children, yet establishment of an EEG biomarker, which is of high importance in clinical practice and research, has not been achieved. In this work, task-related EEG recordings from 61 ADHD and 60 age-matched non-ADHD children are analyzed to examine the underlying Cross-Frequency Coupling phenomena. The proposed framework introduces personalized brain rhythm extraction in the form of oscillatory modes via Swarm Decomposition, allowing for the transition from sensor-level connectivity to source-level connectivity. Oscillatory modes are then subjected to a phase locking value-based feature extraction and the efficiency of the extracted features in separating ADHD from non-ADHD individuals is evaluated by means of a nested 5-fold cross validation scheme. The experimental results of the proposed framework (Area Under the Receiver Operating Characteristics Curve-AUROC: 0.9166) when benchmarked against the commonly used filter-based brain rhythm extraction (AUROC: 0.8361) underscore its efficiency and demonstrate its overall superiority over other state-of-the-art functional connectivity approaches in this classification task for this dataset.Clinical relevance-This framework provides novel insights about brain regions of interest that are involved in ADHD task-related function and holds promise in providing objective ADHD biomarkers by extending classic sensor-level connectivity to source-level.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Encéfalo , Electroencefalografía/métodosRESUMEN
Background: A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function. Objective: To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm). Design: Systematic review and network meta-analysis. Data sources: Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews. Review methods: Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research. Results: Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified (nâ ≥â 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included (nâ =â 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials. Limitations: Many studies were small and of poor quality. No comparative studies were found for some therapies. Conclusions: The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection. Study registration: PROSPERO CRD42020221357. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in Health Technology Assessment; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Hepatocellular carcinoma is the most common type of primary liver cancer. There are a range of different treatments available for patients with early hepatocellular carcinoma. We looked for clinical trials in patients with small tumours (up to 3 cm) that compared different treatments. We brought together and analysed the results of these trials to see which treatments were most effective in terms of survival, progression, side effects and quality of life. Overall, the evidence has limitations; many trials had few patients and were of poor quality. Most were from China or Japan, where the common causes of liver disease and treatments available differ from those in the United Kingdom. The results of our analyses were very uncertain so we cannot be sure which treatment is the best overall. We did find that three treatments radiofrequency ablation, microwave ablation and surgery were generally more effective than percutaneous ethanol injection and percutaneous acid injection. There was not enough evidence to be certain which treatment was better when radiofrequency ablation was compared with laser ablation, microwave ablation, proton beam therapy or surgery. We found only poor-quality, non-randomised trials on high-intensity focused ultrasound, cryoablation and irreversible electroporation. There was very little evidence on treatments that combined radiofrequency ablation with other therapies. We found no studies that compared electrochemotherapy, histotripsy, stereotactic ablative radiotherapy or wider radiotherapy techniques with other treatments. Only two studies reported data on quality of life or patient satisfaction. We discussed the findings with patients and clinical experts. Stereotactic ablative radiotherapy was highlighted as a treatment that requires further research; however, it is only appropriate for certain subgroups of patients. Feasibility studies could inform future clinical trials by exploring issues such as whether patients are willing to take part in a trial or find the treatments acceptable.
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Técnicas de Ablación , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Etanol/uso terapéutico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Metaanálisis en Red , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The stratum corneum (SC) is the skin's outermost layer, organized by clusters of corneocytes among a lipid matrix, acting as a barrier. This "brick and mortar" organization is modified in many skin diseases. We proposed a lesioned-skin model for assessing the permeability of topical formulations and the impact of skin integrity on the permeability of molecules. We anticipate that removal of the SC compromises the skin barrier function, making it more permeable, affecting the biopharmaceutics of topical formulations. By stripping with 25 strips (Corneofix®), the thickness of the SC was considerably reduced, exposing the viable epidermis. Transversal and upper views of the skin by electronic microscopy and histology confirm the removal of the SC. After, we evaluated the permeability of tacrolimus (Protopic®, 0.1 % and 0.03 %) by HPLC-UV. The non-lesioned skin presented 20-25 % of tacrolimus in the SC and no drug permeated through the skin's inner layers. Contrary, the lesioned-skin model allowed the permeation of tacrolimus to the epidermis, dermis, and also in the receptor medium. These results highlight the importance of using diseased skin tissue as opposed to normal skin when assessing the permeability of pharmaceutical formulations for local topical delivery, closely mimicking the occurred events in clinical scenario.
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Enfermedades de la Piel , Tacrolimus , Humanos , Preparaciones Farmacéuticas , Tacrolimus/farmacología , Piel , Epidermis , PermeabilidadRESUMEN
BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. OBJECTIVES: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. MAIN RESULTS: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. AUTHORS' CONCLUSIONS: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
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Trastorno de Pánico , Inhibidores de Captación de Serotonina y Norepinefrina , Adulto , Humanos , Trastorno de Pánico/tratamiento farmacológico , Trastorno de Pánico/complicaciones , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Paroxetina/uso terapéutico , Fluoxetina/uso terapéutico , Clorhidrato de Venlafaxina/uso terapéutico , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéutico , Alprazolam/uso terapéutico , Clomipramina/uso terapéutico , Reboxetina/uso terapéutico , Clonazepam/uso terapéutico , Desipramina/uso terapéutico , Metaanálisis en Red , Antidepresivos/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Benzodiazepinas/uso terapéutico , Diazepam/uso terapéuticoRESUMEN
OBJECTIVES: The Reminiscence Functions Scale (RFS) is a widely used robust instrument. While reminiscence-based intervention is one of the most effective nonpharmacological interventions for older adults. This systematic review provides a comprehensive synthesis of the literature that used RFS with older adults, summarizes the main outcomes, and highlights implications for practice. METHODS: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were eligible if they used RFS and included older adults. Studies were searched from 1993, the year RFS was first published. Electronic databases were searched (Scopus, PsycNET, and Web of Science), from which 44 eligible studies were identified. RESULTS: Four themes were identified: i) predictive value of reminiscence functions regarding well-being, ii) increased frequency of teach/inform and death preparation functions in older adults, iii) key roles of reminiscence functions in coping with critical life events, iv) reminiscence-based interventions should promote positive memories. CONCLUSIONS: The RFS outcomes may improve reminiscence-based interventions, since the functions of reminiscence are key players in older adults daily life. CLINICAL IMPLICATIONS: Reminiscence-based interventions should promote positive memories, which are associated with improved well-being. Particularly, it seems a good practice when supporting older adults regarding critical and traumatic events.
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BACKGROUND & AIMS: Non-surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta-analysis (NMA) was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC. METHODS: Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non-surgical therapy versus any comparator in patients with HCC ≤3 cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence. RESULTS: Thirty-seven eligible RCTs were included (including over 3700 patients). Most were from China (n = 17) or Japan (n = 7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16-1.82), progression-free survival (HR: 1.36, 95% CrI: 1.11-1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02-1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19-2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons. CONCLUSIONS: It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Metaanálisis en Red , Resultado del Tratamiento , Neoplasias Hepáticas/patología , China , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Inhaled corticosteroids (ICS) are the mainstay treatment for persistent asthma. Escalating treatment is required when asthma is not controlled with ICS therapy alone, which would include, but is not limited to, adding a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA) or doubling the dose of ICS. OBJECTIVES: To assess the efficacy and safety of adding a LABA or LAMA to ICS therapy versus doubling the dose of ICS in adolescents and adults whose asthma is not well controlled on medium-dose (MD)-ICS using a network meta-analysis (NMA), and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, Global Health, ClinicalTrials.gov, and the World Health Organization ICTRP for pre-registered randomised controlled trials (RCTs) from January 2008 to 19 December 2022. SELECTION CRITERIA: We searched for studies including adolescents and adults with uncontrolled asthma who had been treated with or were eligible for MD-ICS, comparing it to high-dose (HD)-ICS, ICS/LAMA, or ICS/LABA. We excluded cluster- and cross-over RCTs. Studies were of at least 12 weeks duration. DATA COLLECTION AND ANALYSIS: We conducted a systematic review and network meta-analysis according to a previously published protocol. We used Cochrane's Screen4ME workflow to assess search results. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. The primary outcome is asthma exacerbations (moderate and severe). MAIN RESULTS: We included 38,276 participants from 35 studies (median duration 24 weeks (range 12 to 78); mean age 44.1; 38% male; 69% white; mean forced expiratory volume in one second 2.1 litres and 68% of predicted). MD- and HD-ICS/LABA likely reduce and MD-ICS/LAMA possibly reduces moderate to severe asthma exacerbations compared to MD-ICS (hazard ratio (HR) 0.70, 95% credible interval (CrI) 0.59 to 0.82; moderate certainty; HR 0.59, 95% CrI 0.46 to 0.76; moderate certainty; and HR 0.56, 95% CrI 0.38 to 0.82; low certainty, respectively), whereas HD-ICS probably does not (HR 0.94, 95% CrI 0.70 to 1.24; moderate certainty). There is no clear evidence to suggest that any combination therapy or HD-ICS reduces severe asthma exacerbations compared to MD-ICS (low to moderate certainty). This study suggests no clinically meaningful differences in the symptom or quality of life score between dual combinations and monotherapy (low to high certainty). MD- and HD-ICS/LABA increase or likely increase the odds of Asthma Control Questionnaire (ACQ) responders at 6 and 12 months compared to MD-ICS (odds ratio (OR) 1.47, 95% CrI 1.23 to 1.76; high certainty; and OR 1.59, 95% CrI 1.31 to 1.94; high certainty at 6 months; and OR 1.61, 95% CrI 1.22 to 2.13; moderate certainty and OR 1.55, 95% CrI 1.20 to 2.00; high certainty at 12 months, respectively). MD-ICS/LAMA probably increases the odds of ACQ responders at 6 months (OR 1.32, 95% CrI 1.11 to 1.57; moderate certainty). No data were available at 12 months. There is no clear evidence to suggest that HD-ICS increases the odds of ACQ responders or improves the symptom or qualify of life score compared to MD-ICS (very low to high certainty). There is no evidence to suggest that ICS/LABA or ICS/LAMA reduces asthma-related or all-cause serious adverse events (SAEs) compared to MD-ICS (very low to high certainty). HD-ICS results in or likely results in little or no difference in the included safety outcomes compared to MD-ICS as well as HD-ICS/LABA compared to MD-ICS/LABA. The pairwise meta-analysis shows that MD-ICS/LAMA likely reduces all-cause adverse events (AEs) and results in a slight reduction in treatment discontinuation due to AEs compared to MD-ICS (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.77 to 0.96; 4 studies, 2238 participants; moderate certainty; and RR 0.51, 95% CI 0.26 to 0.99; 4 studies, 2239 participants; absolute risk reduction 10 fewer per 1000 participants; moderate certainty, respectively). The NMA evidence is in agreement with the pairwise evidence on treatment discontinuation due to AEs, but very uncertain on all-cause AEs, due to imprecision and heterogeneity. AUTHORS' CONCLUSIONS: The review findings suggest that MD- or HD-ICS/LABA and MD-ICS/LAMA reduce moderate to severe asthma exacerbations and increase the odds of ACQ responders compared to MD-ICS whereas HD-ICS probably does not. The evidence is generally stronger for MD- and HD-ICS/LABA than for MD-ICS/LAMA primarily due to a larger evidence base. There is no evidence to suggest that ICS/LABA, ICS/LAMA, or HD-ICS/LABA reduces severe asthma exacerbations or SAEs compared to MD-ICS. MD-ICS/LAMA likely reduces all-cause AEs and results in a slight reduction in treatment discontinuation due to AEs compared to MD-ICS. The above findings may assist in deciding on a treatment option during the stepwise approach of asthma management. Longer-term safety of higher than medium-dose ICS needs to be addressed in phase 4 or observational studies given that the median duration of included studies was six months.
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Asma , Antagonistas Muscarínicos , Masculino , Humanos , Adolescente , Adulto , Femenino , Antagonistas Muscarínicos/efectos adversos , Metaanálisis en Red , Asma/tratamiento farmacológico , Corticoesteroides , Terapia CombinadaRESUMEN
Spatial patterns and temporal trends of the butyltin compounds tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) were investigated in a set of sediment samples collected along the SW Portuguese continental shelf. This region did not reach the Good Environmental Status (GES) in accordance with the Marine Strategy Framework Directive (MSFD) during a first evaluation carried out in 2012. Overall, MBT and DBT were the predominant organotin species detected, but high concentrations of TBT were found in and around disposal sites for dredge sludge derived from the dredging in navigation channels, harbours, and shipyard facilities of the Tagus and Sado estuaries. Although Portuguese regulations for monitoring sediment quality in relation to dredging activities consider only PAH, PCB and HCB, they also dictate that other organic contaminants such as butyltin compounds (BTs) should be monitored if suspicion of high values exists, but no action limits are defined for these (MAOTDR, 2007). Without action limits, the monitoring recommendation given in the regulations is not put into practice. Considering their toxicity, BT derivates should be integrated in the legislation, because they represent an environmental threat in the relocation of dredged material, especially when derived from harbour and shipyards areas. Based on this study, we recommend giving more attention to the amounts and impacts of BTs in sediments at dredged material disposal sites (DMDS) and their surroundings. Or even better, in order to be more efficient, monitoring should be done at the source of the dredged materials and not at the sink. In case it is not done, the monitoring of concentrations of TBT (and other BTs) in sediments and organisms, including imposex studies, at all Portuguese sites for disposal of dredged material receiving slightly to strongly contaminated dredged material must be developed.
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Background Opioids have long been the cornerstone of drugs used for perioperative analgesia. Sufentanil has an advantageous pharmacological profile for its use in continuous intravenous (IV) infusion, yet remains poorly described. Our institution has implemented analgesia protocols with IV sufentanil infusions for cancer surgery with appropriate monitoring. The aim of this study was to evaluate the efficacy and safety of IV sufentanil infusion. Methods A single-center retrospective cohort study was conducted through the analysis of patients' records and the acute pain service database. Inclusion criteria were adult patients admitted for elective cancer surgery and with postoperative IV sufentanil infusion during one year period. Descriptive and inferential statistical analysis was performed by using Software SPSS Statistics (IBM Corp., Armonk USA): Kruskal-Wallis, Mann-Whitney, Chi-square and Fisher tests; Bonferroni chi-square residual analysis, binary logistic regression; p<0.05. Results The study population of 304 patients had a median age of 66 years (22-91) and 229 (75.3%) were men. 38 (12.5%) were chronic opioid users. Head and neck/otorhinolaryngology (ORL) surgery was performed in 155 (51.0%) and abdominopelvic surgery in 123 (40.5%). The median days of IV sufentanil infusion were 2 (1-13). At rest and with movement, analgesia was considered good, i.e., over 90% of patients with visual analogue scale (VAS) pain score ≤ 3. We found that patients submitted to musculoskeletal surgery had higher VAS pain scores; this group also presented older patients with higher American Society of Anesthesiologists (ASA) physical status classification and more chronic opioid users (p<0.05). 144 patients (47.4%) had at least one adverse effect related to IV sufentanil infusion, notably transient and not requiring any specific treatment. These patients were older and had longer infusion periods (p<0.05). 237 (98.3%) of the adverse effects occurred during the first 3 days and the most common were: sedation (n=104, 42.8%), hypotension (n=32, 13.2%), hypoxemia (n=31, 12.8%) and nausea/vomiting (n=25, 10.3%). The reported incidence of respiratory depression was 2.9% (n=9), with three patients (1%) requiring advanced treatment. Conclusion Multimodal analgesic protocols with IV sufentanil infusions provided good postoperative analgesia for head and neck/ORL and abdominopelvic cancer surgeries. The adverse effects associated with the IV sufentanil infusions were mild and mainly managed with opioid dose reductions. Our study showed that this approach can be a safe option for postoperative multimodal analgesia in cancer surgery with appropriate monitoring in high-dependency units.