IMPORTANCE Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low.OBJECTIVE To track LDL-C treatment patterns in the US over 2 years. DESIGN, SETTING, AND PARTICIPANTS GOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020. MAIN OUTCOMES AND MEASURESThe primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years.RESULTS A total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels Ն100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P < .001) and achievement of LDL-C less than 70 mg/dL (teaching vs nonteaching hospitals, 173 of 488 [35.5%] vs 823 of 2986 [27.6%]; lipid protocols vs none, 451 of 1411 [32.0%] vs 545 of 2063 [26.4%]; both P < .001; cardi...
Background The diagnosis of infectious diseases has been hampered by reliance on microbial culture. Cultures take several days to return a result and organisms frequently fail to grow. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and mitigates against stewardship. Methods Single ICU observational cohort study with contemporaneous comparator group. We developed and implemented a TaqMan array card (TAC) covering 52 respiratory pathogens in ventilated patients undergoing bronchoscopic investigation for suspected pneumonia. The time to result was compared against conventional culture, and sensitivity compared to conventional microbiology and metagenomic sequencing. We observed the clinician decisions in response to array results, comparing antibiotic free days (AFD) between the study cohort and comparator group. Findings 95 patients were enrolled with 71 forming the comparator group. TAC returned results 61 hours (IQR 42-90) faster than culture. The test had an overall sensitivity of 93% (95% CI 88-97%) compared to a combined standard of conventional culture and metagenomic sequencing, with 100% sensitivity for most individual organisms. In 54% of cases the TAC results altered clinical management, with 62% of changes leading to de-escalation, 30% to an increase in spectrum, and investigations for alternative diagnoses in 9%. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). Interpretation Implementation of a customised syndromic diagnostic for pneumonia led to faster results, with high sensitivity and measurable impact on clinical decision making. Funding Addenbrookes Charitable Trust, Wellcome Trust and Cambridge NIHR BRC
Adipose tissue senescence is implicated as a major player in obesity- and ageing-related disorders. There is a growing body of research studying relevant mechanisms in age-related diseases, as well as the use of adipose-derived stem cells in regenerative medicine. The cell banking of tissue by utilising cryopreservation would allow for much greater flexibility of use. Dimethyl sulfoxide (DMSO) is the most commonly used cryopreservative agent but is toxic to cells. Trehalose is a sugar synthesised by lower organisms to withstand extreme cold and drought that has been trialled as a cryopreservative agent. To examine the efficacy of trehalose in the cryopreservation of human adipose tissue, we conducted a systematic review of studies that used trehalose for the cryopreservation of human adipose tissues and adipose-derived stem cells. Thirteen articles, including fourteen studies, were included in the final review. All seven studies that examined DMSO and trehalose showed that they could be combined effectively to cryopreserve adipocytes. Although studies that compared nonpermeable trehalose with DMSO found trehalose to be inferior, studies that devised methods to deliver nonpermeable trehalose into the cell found it comparable to DMSO. Trehalose is only comparable to DMSO when methods are devised to introduce it into the cell. There is some evidence to support using trehalose instead of using no cryopreservative agent.
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