Clinical vs. autopsy diagnostic discrepancies in the intensive care unit: a systematic review and meta-analysis of autopsy series.

PURPOSE: The aim of this study was to assess whether there is a discrepancy between clinical and autopsy-based diagnoses in adult intensive care unit (ICU) patients. METHODS: We conducted a systematic review of cohort studies reporting on conventional autopsy-confirmed missed diagnoses. The discrepancy rate was per study calculated by dividing the number of patients with a missed diagnosis by the number of autopsies. Missed diagnoses were classified according to the Goldman classification as 'major' and 'minor' with major missed diagnoses further differentiated into Class I missed diagnoses (i.e., diagnoses that may have altered therapy or survival) and Class II missed diagnoses (i.e., diagnoses that would not have altered therapy or survival). Class I missed diagnoses constitute the primary outcome of interest. Pooled estimates for discrepancy rates (95% confidence intervals) were calculated using a mixed-effects logistic regression model with 'study' as random effect. Meta-regression was used to assess relationships between major discrepancy rates and autopsy rates, start year of study, and ICU type. RESULTS: Forty-two studies were identified totaling 6305 analyzed autopsies and 1759 patients with missed diagnoses. The pooled discrepancy rates for Class I and major missed diagnoses were 6.5% (5-8.5) and 19.3% (15.3-24), respectively. Meta-regression analysis revealed that autopsy rate was inversely associated with discrepancy rate. Class I discrepancy rates did not change over time. Burn and trauma ICUs had lower discrepancy rates as compared to medical ICUs, possibly because of higher autopsy rates. CONCLUSIONS: Missed diagnoses remain common in ICUs. A higher autopsy rate does not reveal more major diagnostic errors. These data support a clinically driven autopsy policy rather than a systematic autopsy policy.

Ocriplasmin for treatment of vitreomacular traction and macular hole: A systematic literature review and individual participant data meta-analysis of randomized, controlled, double-masked trials.

Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's effect on vitreomacular adhesion resolution (VMAR), MH closure, vitrectomy, and best-corrected visual acuity (BCVA) and investigated the effect of baseline covariates on outcome. We applied individual participant data meta-analyses to the entire population and to subgroups defined by MH or epiretinal membrane (ERM) presence. Safety data were pooled and tabulated. Five randomized controlled trials (1,067 participants) were included. Six months after treatment, ocriplasmin achieved higher rates of VMAR and MH closure versus control, lowered vitrectomy odds, and increased the likelihood of a ≥10-letter BCVA increase. VMAR rates were lower when ERM, broad VMA (> 1500 µm), diabetic retinopathy, or pseudophakia were present and higher in younger participants, women, and eyes with MHs. Ocriplasmin-treated participants experienced more short-term visual impairment that was not predictive of final BCVA, as well as vitreous floaters, photopsia, photophobia, eye pain, blurred vision, and dyschromatopsia. The most common serious adverse events for ocriplasmin and control, respectively, were MH progression (22.5%, 17.3%), new MH (1.5%, 3.4%) and retinal detachment (0.8%, 1.2%). Ocriplasmin promotes VMAR and MH closure. Transient visual phenomena are not uncommon.

Effectiveness of ocriplasmin in real-world settings: A systematic literature review, meta-analysis, and comparison with randomized trials.

PURPOSE: Effectiveness of ocriplasmin for vitreomacular traction (VMT) varies depending on the presence of common ocular conditions and patient selection criteria. We carried out a systematic literature review and meta-analysis of ocriplasmin studies conducted in real-world settings (RWS) and compared outcomes with those from randomized controlled trials (RCTs). METHODS: We included prospective and retrospective studies from RWS documenting effectiveness of ocriplasmin in patients with VMT with or without MH, and RCTs of ocriplasmin versus control. Key end-points were vitreomacular adhesion resolution (VMAR), nonsurgical MH closure, need for vitrectomy and safety. We conducted meta-regression on pooled results to evaluate effects of baseline covariates and study design on outcomes. RESULTS: Thirty RWS (2402 patients) and 5 RCTs (737 patients) were included epiretinal membrane (ERM) and broad VMA were more prevalent in RCTs. Primary VMAR, vitrectomy and MH closure rates were comparable between RWS and RCTs. Rates of nsVMAR were significantly higher in RWS than RCTs (odds ratio 1.66; 95% confidence interval [CI]: 1.18-2.34). nsVMAR rates were inversely associated with ERM prevalence (odds ratio 0.20; 95% CI: 0.08-0.51). Compared with the recent OASIS trial, RWS reported a higher incidence of new/worsening subretinal fluid cases and less photophobia, photopsia, vitreous floaters, electroretinogram abnormalities and MH progression. CONCLUSIONS: Ocriplasmin was significantly more effective in achieving nsVMAR in RWS than in RCTs. Lower ERM prevalence in RWS was the single significant explanatory variable for this difference. Conclusions on ocriplasmin safety in RWS are limited due to inconsistent reporting.