A strength of this review is the integration of laboratory-based expectancy paradigms with clinically embedded studies across multiple long-term conditions. Detailed extraction of statistical approach

The gap

Consensus across the literature

Supporting evidence — 3 representative gaps

• Association of compliance-normalized airway and transpulmonary mechanical power with mortality in PARDS (2026) · doi

  Several limitations should be considered when interpret- ing these findings. The observational design does not allow causal inference regarding the relationship between mechan- ical power and mortality, and residual confounding cannot be excluded despite multivariable adjustment. In addition, the relatively limited number of outcome events compared with the number of covariates may have reduced the preci- sion of the multivariable estimates, as reflected by the wide confidence intervals observed in some models. This may also have affected model stability and the reliability of the estimated effect sizes. Accordingly, the observed independ- ent associations should be interpreted with caution and are best considered hypothesis-generating rather than definitive. Physiological and ventilatory measurements were obtained at a single early time point. Mechanical power represents a dynamic exposure that may evolve over the course of ill- ness, and this analysis does not account for cumulative or time-weighted exposure or changes in ventilatory manage- ment over time. This may attenuate the strength of observed associations and preclude a more precise evaluation of tem- poral relationships between mechanical power and clinical outcomes. Ventilator-free days represent a composite out- come influenced by the competing risk of mortality, and correlation-based analyses should therefore be interpreted with caution. The number of subjects with severe PARDS in the present cohort was relatively small, which may partly explain the lower mortality observed in this subgroup com- pared with previously reported PARDS cohorts. Although the direction of the associations remained consistent across analyses, external validation in larger and independent pedi- atric cohorts is required. Mechanical power was calculated using a simplified equation for pressure-controlled ventila- tion, which may not fully capture the complexity of pressure and flow waveforms. Normalization of mechanical power to body surface area was prespecified as exploratory; although this approach demonstrated consistent associations in uni- variable and physiological analyses, its clinical relevance and generalizability require confirmation across broader age ranges and ventilatory strategies. Finally, the study was conducted in tertiary pediatric intensive care units with advanced monitoring capabilities. European Journal of Pediatrics (2026) 185:393 Page 11 of 12 393 Therefore, the applicability of transpulmonary-based indi- ces may be limited in centers without routine esophageal manometry. Although esophageal pressure measurements were part of routine practice at the participating centers, exclusion of patients without reliable measurements or complete datasets may have introduced selection bias. While transpulmonary measurements provide a more direct assessment of lung-specific mechanics, their rou- tine use remains limited in many clinical settings. In this context, airway compliance-normalized mechanical power, derived from routinely available ventilator parameters, may represent a more broadly applicable surrogate for estimating ventilatory stress. The consistency of findings between airway and transpulmonary indices supports the potential clinical utility of airway-based measures, while transpulmonary measurements may offer additional physi- ological refinement in specialized centers.

  Keywords: power measurements mechanical observed associations ventilatory clinical transpulmonary mortality limited number time based analyses pressure
• Nocebo effects in long-term health conditions: a systematic review of experimental studies (2026) · doi

  A strength of this review is the integration of laboratory-based expectancy paradigms with clinically embedded studies across multiple long-term conditions. Detailed extraction of statistical approaches and moderator analyses enhances transparency regard- ing evidential strength. The inclusion of both subjective and physiological outcomes allows consideration of mechanis- tic breadth. Limitations include heterogeneity of design and outcome mea- surement, inconsistent reporting of standardised effect sizes, and generally modest sample sizes. The absence of meta-analysis limits quantitative precision. Additionally, many studies examined short- term or experimentally induced outcomes rather than long-term disease trajectories, constraining inference regarding sustained clinical impact. Methodologically, several features constrain interpretation. Standardised effect sizes were infrequently reported, despite statis- tically significant findings in multiple studies, with most analyses relying on p-values, F statistics, or regression coefficients without accompanying standardised indices (24–26, 30–32, 35). This limits cross-study comparison and precludes quantitative synthesis. Sample sizes were often modest, particularly in laboratory-based paradigms, increasing vulnerability to both Type I and Type II error. Designs varied considerably, including analogue online studies, laboratory induction paradigms, and clinical trials embed- ded within treatment contexts. While this enhances ecological breadth, it reduces methodological uniformity. The search strategy was intentionally anchored to the concep- tual construct of the nocebo effect rather than to a broad array of loosely related expectancy terms. This approach prioritised con- ceptual specificity and theoretical coherence. However, variability in terminology across clinical and experimental literatures means that

  Keywords: sizes laboratory paradigms term standardised effect clinical strength based expectancy across multiple long analyses enhances
• Diaphragmatic ultrasonography parameters during waveform-defined double triggering asynchrony in mechanically ventilated critically ill patients (2026) · doi

  This study has several limitations. First, double trigger- ing was identified by ventilator waveform analysis alone, without concurrent esophageal pressure (Pes) or electri- cal activity of the diaphragm (EAdi) monitoring, which are the gold standards for physiologic confirmation of patient–ventilator asynchrony. Therefore, misclassifi- cation cannot be excluded, and the findings should be interpreted as applying to waveform-defined double trig- gering rather than physiologically confirmed asynchrony. Second, the sample size was small, which limits statis- tical power, reduces the stability of ROC-derived cutoff values, and restricts generalizability. Therefore, the pro- posed thresholds should be considered exploratory and should not be extrapolated to broader ICU populations without external validation. Third, the correction of double triggering was not stan- dardized. Different ventilator adjustments, with addi- tional sedation and/or analgesia titration when clinically indicated, were applied according to bedside judgment, often in combination. As a result, the observed changes in diaphragmatic ultrasound parameters should be inter- preted as reflecting overall restoration of synchrony rather than the isolated effect of any single intervention. Fourth, sedation and analgesia remain potential con- founders because they may influence diaphragmatic contractility, inspiratory drive, thickening fraction, and excursion duration, thereby affecting diaphragmatic ultrasound measurements and their interpretation. Fifth, driving pressure was not systematically calcu- lated in this study. In the pressure-control subgroup, PEEP was fixed and applied inspiratory pressures did not differ significantly between states, rendering any calcu- lated airway driving pressure essentially unchanged. In the volume-control subgroup, accurate plateau pressure measurements were unavailable at both time points due to severe patient-ventilator asynchrony and spontaneous respiratory efforts. Consequently, our findings lack data on transpulmonary or airway driving pressures, which could have provided additional physiological insights into the transition from asynchrony to synchrony.

  Keywords: pressure ventilator asynchrony double diaphragmatic driving waveform without patient rather sedation analgesia applied ultrasound synchrony