Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials.

BACKGROUND: Previous meta-analyses have shown that statins may cause incident diabetes. This article reviews randomized controlled trials using proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) or ezetimibe on the risk of new-onset diabetes. METHODS: Eight trials involving PCSK9i and 3 trials of ezetimibe were selected for review. PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were thoroughly searched for relevant trials. Inclusion criteria included at least 100 patients per treatment arm, follow-up of at least 52 weeks, and at least double-blinded study design. Exclusion criteria included patients with previously diagnosed diabetes, nonrandomized, placebo-controlled, open-label, and crossover trials. The primary outcome was the number of incident diabetes cases. A random effects model was used. Heterogeneity in effect sizes was measured with I2 parameter and the Q statistic was used to test for excessive between-study heterogeneity. RESULTS: A total of 52 214 participants for the PCSK9i and a total of 20 084 for the ezetimibe meta-analyses were included. Participants randomized to PCSK9i did not differ from the control patients in diabetes incidence (risk ratio [RR] = 0.99, P = .87, 95% CI = 0.92-1.07). Participants randomized to ezetimibe did not differ from the control patients in diabetes incidence (RR = 1.05, P = .37, 95% CI = 0.95-1.15). DISCUSSION: The use of PCSK9i and ezetimibe does not appear to impact the risk of incident diabetes mellitus when added to guideline-directed medical therapy.

Data availability and feasibility of various techniques to predict response to volume expansion in critically ill patients.

OBJECTIVE: The accuracy of various techniques to predict response to volume expansion in shock has been studied, but less well known is how feasible these techniques are in the ICU. METHODS: This is a prospective observation single-center study of inpatients from a mixed profile ICU who received volume expansion. At time of volume expansion, we determined whether a particular technique to predict response was feasible, according to rules developed from available literature and nurse assessment. RESULTS: We studied 214 volume expansions in 97 patients. The most feasible technique was central venous pressure (50%), followed by vena cava collapsibility, (47%) passive leg raise (42%), and stroke volume variation (22%). Aortic velocity variation, and pulse pressure variation, and were rarely feasible (1% each). In 37% of volume expansions, no technique that we assessed was feasible. CONCLUSIONS: Techniques to predict response to volume expansion are infeasible in many patients in shock.

Long-term outcomes after severe shock.

Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 µg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely critically ill patients have similar outcomes to general intensive care unit survivor populations.

Glasgow Coma Scale score dominates the association between admission Sequential Organ Failure Assessment score and 30-day mortality in a mixed intensive care unit population.

OBJECTIVE: The Sequential Organ Failure Assessment (SOFA) score, a measure of multiple-organ dysfunction syndrome, is used to predict mortality in critically ill patients by assigning equally weighted scores across 6 different organ systems. We hypothesized that specific organ systems would have a greater association with mortality than others. DESIGN: We retrospectively studied patients admitted over a period of 4.2 years to a mixed-profile intensive care unit (ICU). We recorded age and comorbidities, and calculated SOFA organ scores. The primary outcome was 30-day all-cause mortality. We determined which organ subscores of the SOFA score were most associated with mortality using multiple analytic methods: random forests, conditional inference trees, distanced-based clustering techniques, and logistic regression. SETTING: A 24-bed mixed-profile adult ICU that cares for medical, surgical, and trauma (level 1) patients at an academic referral center. PATIENTS: All patients' first admission to the study ICU during the study period. MEASUREMENTS AND MAIN RESULTS: We identified 9120 first admissions during the study period. Overall 30-day mortality was 12%. Multiple analytical methods all demonstrated that the best initial prediction variables were age and the central nervous system SOFA subscore, which is determined solely by Glasgow Coma Scale score. CONCLUSIONS: In a mixed population of critically ill patients, the Glasgow Coma Scale score dominates the association between admission SOFA score and 30-day mortality. Future research into outcomes from multiple-organ dysfunction may benefit from new models for measuring organ dysfunction with special attention to neurologic dysfunction.