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Background: Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients’ prognostic factors, potentially leading to bias when comparing real-world treatment effects. Methods: Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015–June 2020 for patients aged ≥18 years in Optum’s de-identified Clinformatics Data Mart (CDM) and MarketScan, and those aged ≥66 in the US Medicare claims database. We estimated a 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone–censor–weight approach to address time-varying confounding and immortal person-time. Results: PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = −3.6% [95% CI: −4.3%, −2.9%]), decubitus ulcer (RD = −7.7% [95% CI: −11.8%, −3.7%]), fracture (RD = −8.1% [95% CI: −9.6%, −6.6%]), influenza vaccine (RD = −9.3% [95% CI: −17.5%, −1.1%]), and visual test (RD = −0.6% [95% CI: −0.7%, −0.6%]) under the PCSK9 mAb initiation versus no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies. Conclusion: A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators. [ABSTRACT FROM AUTHOR]

Background Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART). Methods We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months. Results Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22–30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15–34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16–43%) infants in the POC group vs 7 (19%; 6–32%) in the SOC group (RR: 1.56;.7–3.50). Conclusions POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes. Clinical Trials Registration This trial is registered at https://clinicaltrials.gov (NCT02682810). [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with non‐alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis. Aims To investigate the completeness of real‐world NASH‐related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy‐diagnosed NASH and a pragmatic clinical definition of NASH. Methods: Liver pathology reports from 222 patients across 38 TARGET‐NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over‐read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET‐NASH clinically defined NASH: elevated ALT, hepatic steatosis on biopsy or imaging and ≥1 of the following: BMI ≥30 kg/m2, type 2 diabetes mellitus and dyslipidaemia. Results: Documentation of steatosis, lobular inflammation, portal inflammation and ballooning were missing from 21%, 35%, 46% and 40% of reports, respectively. There was slight‐to‐fair concordance (weighted kappa 0.01‐0.35) between site and central pathologists for inflammatory features, and moderate concordance (weighted kappa 0.56‐0.57) for fibrosis staging. Clinical definition of NASH was 75%‐91% concordant (94%‐95% sensitive) with biopsy‐diagnosed NASH. Conclusions: There is substantial variability in reporting and grading NASH and fibrosis staging in clinical practice. This heterogeneity may adversely impact patient assessment and translation of practice guidelines into reality. The TARGET‐NASH pragmatic clinical definition may serve as a valuable tool to accurately identify NASH patients in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART)., Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months., Results: Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22-30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6-2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15-34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16-43%) infants in the POC group vs 7 (19%; 6-32%) in the SOC group (RR: 1.56; .7-3.50)., Conclusions: POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes., Clinical Trials Registration: This trial is registered at https://clinicaltrials.gov (NCT02682810)., Competing Interests: Potential conflicts of interest. J. S. A. S. reports support from the Bill and Melinda Gates Foundation, outside the submitted work. All other authors report no potential conflicts. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)