Summary In the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing hepatitis B virus (HBV)-associated liver disease, including hepatocellular carcinoma (HCC). Recently published ...studies show that in CHB patients treated with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies including matched untreated controls, current NA therapy consistently resulted in a significantly lower HCC incidence in patients with cirrhosis, amounting to an overall HCC risk reduction of ∼30%; in non-cirrhotic patients, HCC risk reduction was overall ∼80%, but this was only observed in some studies. For patients of Caucasian origin, no appropriate comparative studies are available to date to evaluate the impact of NA treatment on HCC. Achievement of a virologic response under current NA therapy was associated with a lower HCC risk in Asian, but not Caucasian studies. Studies comparing entecavir or tenofovir with older NAs generally found no difference in HCC risk reduction between agents, except for one study which used no rescue therapy in patients developing lamivudine resistance. Overall, these data indicate that with the current, potent NAs, HCC risk can be reduced but not eliminated, probably due to risk factors that are not amenable to change by antiviral therapy, or events that may have taken place before treatment initiation. Validated pre- and on-therapy HCC risk calculators that inform the best practice for HCC surveillance and facilitate patient counseling would be of great practical value.
In cooperation with the Core Outcome Measures in Effectiveness Trials (COMET) initiative, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative aimed ...to develop a guideline on how to select outcome measurement instruments for outcomes (i.e., constructs or domains) included in a "Core Outcome Set" (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population.
Informed by a literature review to identify potentially relevant tasks on outcome measurement instrument selection, a Delphi study was performed among a panel of international experts, representing diverse stakeholders. In three consecutive rounds, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments, to justify their choices, and to add other relevant tasks. Consensus was defined as being achieved when 70 % or more of the panelists agreed and when fewer than 15 % of the panelists disagreed.
Of the 481 invited experts, 120 agreed to participate of whom 95 (79 %) completed the first Delphi questionnaire. We reached consensus on four main steps in the selection of outcome measurement instruments for COS: Step 1, conceptual considerations; Step 2, finding existing outcome measurement instruments, by means of a systematic review and/or a literature search; Step 3, quality assessment of outcome measurement instruments, by means of the evaluation of the measurement properties and feasibility aspects of outcome measurement instruments; and Step 4, generic recommendations on the selection of outcome measurement instruments for outcomes included in a COS (consensus ranged from 70 to 99 %).
This study resulted in a consensus-based guideline on the methods for selecting outcome measurement instruments for outcomes included in a COS. This guideline can be used by COS developers in defining how to measure core outcomes.
New knowledge about male–female differences in pathophysiology, diagnosis, and treatment is shifting the practice of medicine from a one-size-fits all approach to a more individualized process that ...considers sex-specific interventions at the point of care. In this article, we review how clinical practice guideline committees can incorporate a structured framework to determine whether sex-specific assessments of the quality of the evidence or the particular recommendations should be made. The process can be operationalized by societies who author clinical practice guidelines by developing formal policies to approach biological sex in a systematic way, and by ensuring that writing committees include an individual who will champion the formal appraisal of the literature for associations between sex and the outcomes of interest. Ongoing challenges are discussed, and solutions are provided for how to disaggregate the evidence, how to assess bias, how to improve search strategies, and what to do when the data are insufficient to make sex-specific recommendations. Application of sex-specific recommendations will involve routinely asking whether the presentation, diagnostic workup, or management might change for each patient if they were the opposite sex.
Les nouvelles connaissances sur les différences homme-femme en matière de physiopathologie, de diagnostic et de traitement réorientent la pratique de la médecine pour passer d’une approche universelle à un processus plus individualisé qui considère les interventions en fonction du sexe au point d’intervention. Dans le présent article, nous passons en revue la façon dont les comités sur les lignes directrices de pratique clinique peuvent intégrer un cadre structuré pour déterminer si des évaluations de la qualité des données probantes en fonction du sexe ou si des recommandations particulières devraient être faites. Le processus peut être mis en œuvre par les sociétés qui rédigent les lignes directrices de pratique clinique en élaborant des politiques formelles pour aborder de manière systématique le sexe biologique et en s’assurant que les comités de rédaction regroupent des individus qui soutiendront l’évaluation formelle de la littérature sur les associations entre le sexe et les critères d’intérêt. Nous traitons des enjeux actuels, et nous donnons des solutions sur la manière de désagréger les données probantes, sur la manière d’évaluer les biais, sur la manière d’améliorer les stratégies de recherche et sur ce qu’il faut faire lorsque les données sont insuffisantes pour formuler des recommandations en fonction du sexe. L’application de recommandations en fonction du sexe obligera à se demander systématiquement s’il est possible que le tableau clinique, le bilan diagnostique ou la prise en charge aient varié pour chacun des patients s’ils avaient été de sexe opposé.
A broad array of transdiagnostic psychological treatments for depressive and anxiety disorders have been evaluated, but existing reviews of this literature are restricted to face-to-face cognitive ...behavioural therapy (CBT) protocols. The current meta-analysis focused on studies evaluating clinician-guided internet/computerised or face-to-face manualised transdiagnostic treatments, to examine their effects on anxiety, depression and quality of life (QOL). Results from 50 studies showed that transdiagnostic treatments are efficacious, with large overall mean uncontrolled effects (pre- to post-treatment) for anxiety and depression (gs=.85 and .91 respectively), and medium for QOL (g=.69). Uncontrolled effect sizes were stable at follow-up. Results from 24 RCTs that met inclusion criteria showed that transdiagnostic treatments outperformed control conditions on all outcome measures (controlled ESs: gs=.65, .80, and .46 for anxiety, depression and QOL respectively), with the smallest differences found compared to treatment-as-usual (TAU) control conditions. RCT quality was generally poor, and heterogeneity was high. Examination of the high heterogeneity revealed that CBT protocols were more effective than mindfulness/acceptance protocols for anxiety (uncontrolled ESs: gs=.88 and .61 respectively), but not depression. Treatment delivery format influenced outcomes for anxiety (uncontrolled ESs: group: g=.70, individual: g=.97, computer/internet: g=.96) and depression (uncontrolled ESs: group: g=.89, individual: g=.86, computer/internet: g=.96). Preliminary evidence from 4 comparisons with disorder-specific treatments suggests that transdiagnostic treatments are as effective for reducing anxiety, and may be superior for reducing depression. These findings show that transdiagnostic psychological treatments are efficacious, but higher quality research studies are needed to explore the sources of heterogeneity amongst treatment effects.
•Transdiagnostic (TD) treatments have large effects on anxiety and depression.•TD-CBT has been most widely evaluated, followed by mindfulness-based treatments.•Medium to large comparative group differences between TD treatments and control conditions•Type of treatment, delivery format, and type of control condition influenced outcomes.•More comparisons are needed with TAU controls, and across treatment types.
Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe.Design Retrospective cohort study.Setting Publicly accessible ...regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs.Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.
We report on the outcome of 114 COVID-19-associated acute respiratory distress syndrome (ARDS) survivors evaluated at 3, 6 and 12 months after intensive care unit discharge with assessment of ...physical, mental and cognitive impairments. Critical illness polyneuromyopathy was diagnosed in 23 patients (39%). Handgrip dynamometry was 70% predicted at 3 months and significantly improved over time, whereas the 6 min walk test (80% predicted) and severe fatigue (27% of patients) did not. Independence in activities of daily living (ADL) was achieved by 98% at 3 months. Cognitive impairment (28% at 3 months) improved over time, whereas depression, anxiety and post-traumatic stress disorder symptoms, present in 9%, 10% and 4% at 3 months, did not. Normalised health-related quality of life was good. COVID-19-associated ARDS leads to persisting impairment in performance-based measures of physical function, while ADL, cognitive and mental health status, and health-related quality of life may be less impaired. Trial registration number NCT04608994.
Clinical photography is an important component of the initial assessment and follow-up of patients with vitiligo in clinical practice and research settings. Standardization of this photographic ...process is essential to achieve useful, high-quality, and comparable photographs over time.
The aim is to develop an international consensus for a core set of recommendations for standardized vitiligo clinical photography.
Based an international meeting of vitiligo experts, a standard operating procedure was developed for vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 vitiligo experts until agreement was reached.
The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described.
This consensus-based protocol for vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.
There is currently no consensus on approaches to defining asthma or assessing asthma outcomes using electronic health record-derived data. We explored these approaches in the recent literature and ...examined the clarity of reporting.We systematically searched for asthma-related articles published between January 1, 2014 and December 31, 2015, extracted the algorithms used to identify asthma patients and assess severity, control and exacerbations, and examined how the validity of these outcomes was justified.From 113 eligible articles, we found significant heterogeneity in the algorithms used to define asthma (n=66 different algorithms), severity (n=18), control (n=9) and exacerbations (n=24). For the majority of algorithms (n=106), validity was not justified. In the remaining cases, approaches ranged from using algorithms validated in the same databases to using nonvalidated algorithms that were based on clinical judgement or clinical guidelines. The implementation of these algorithms was suboptimally described overall.Although electronic health record-derived data are now widely used to study asthma, the approaches being used are significantly varied and are often underdescribed, rendering it difficult to assess the validity of studies and compare their findings. Given the substantial growth in this body of literature, it is crucial that scientific consensus is reached on the underlying definitions and algorithms.
Establishing stable breathing is a key event for preterm infants after birth. Delivery of pressure-stable continuous positive airway pressure and avoiding face mask use could be of importance in the ...delivery room.
To determine whether using a new respiratory support system with low imposed work of breathing and short binasal prongs decreases delivery room intubations or death compared with a standard T-piece system with a face mask.
In this unblinded randomized clinical trial, mothers threatening preterm delivery before week 28 of gestation were screened. A total of 365 mothers were enrolled, and 250 infants were randomized before birth and 246 liveborn infants were treated. The trial was conducted in 7 neonatal intensive care units in 5 European countries from March 2016 to May 2020. The follow-up period was 72 hours after intervention.
Infants were randomized to either the new respiratory support system with short binasal prongs (n = 124 infants) or the standard T-piece system with face mask (n = 122 infants). The intervention was providing continuous positive airway pressure for 10 to 30 minutes and positive pressure ventilation, if needed, with the randomized system.
The primary outcome was delivery room intubation or death within 30 minutes of birth. Secondary outcomes included respiratory and safety variables.
Of 246 liveborn infants treated, the mean (SD) gestational age was 25.9 (1.3) weeks, and 127 (51.6%) were female. A total of 41 infants (33.1%) receiving the new respiratory support system were intubated or died in the delivery room compared with 55 infants (45.1%) receiving standard care. The adjusted odds ratio was statistically significant after adjusting for stratification variables (adjusted odds ratio, 0.53; 95% CI, 0.30-0.94; P = .03). No significant differences were seen in secondary outcomes or safety variables.
In this study, using the new respiratory support system reduced delivery room intubation in extremely preterm infants. Stabilizing preterm infants with a system that has low imposed work of breathing and binasal prongs as interface is safe and feasible.
ClinicalTrials.gov Identifier: NCT02563717.
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