LDL-cholesterol reduction in chronic kidney disease: options beyond statins.

PURPOSE OF REVIEW: Individuals with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) events. LDL cholesterol (LDL-C) is a key modifiable cause of ASCVD and lowering LDL-C with statins reduces the risk of ASCVD events in a wide range of populations, including those with CKD. This review considers the utility of recently developed nonstatin LDL-C-lowering therapies in CKD. RECENT FINDINGS: The cholesterol absorption inhibitor, ezetimibe, reduces LDL-C by 15-20% and is well tolerated in CKD. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) reduce LDL-C by 50-60% and reduce the risk of ASCVD events. However, these agents require self-administration by subcutaneous injection every 2-4 weeks. The PCSK9 synthesis inhibitor, inclisiran, is administered approximately 6 monthly and may be more suitable for widespread use, although outcome trials are awaited. These PCSK9 targeting therapies require no dose adjustment in CKD and have no drug interactions. SUMMARY: Statins and ezetimibe are safe and reduce ASCVD risk in CKD populations. PCSK9 targeting agents may be useful in high-risk CKD patients, including those with prior ASCVD.

Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis.

BACKGROUND: Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against "gold standard" (GS) methods to study the feasibility of using such methods in clinical trials. METHODS: Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves. RESULTS: A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5-98.3), but lacked sensitivity (63.5%, 95% CI 51.3-74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies. CONCLUSIONS: RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.

The importance of positive need fulfillment: Evidence from a sample of war-affected Sri Lankans.

There has been growing interest in understanding the psychological and social-environmental factors that facilitate adaptive functioning in populations affected by ethnopolitical warfare. In the current study, we tested the hypothesis that a brief measure incorporating local idioms of positive need fulfilment would predict functioning in a war-affected Sri Lankan population above and beyond psychopathology when controlling for demographic variables and current life stressors. A brief measure of positive need fulfillment was derived from qualitative data and administered to a sample of 163 Sri Lankans affected by the civil war. Positive need fulfillment was found to uniquely predict functioning after controlling for age, war-related life problems, and psychopathology as assessed by the Penn-RESIST-Peradeniya War Problems Questionnaire. These findings highlight the importance of both basic need support and the fostering of agency in addition to addressing mental health needs. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Are culturally specific measures of trauma-related anxiety and depression needed? The case of Sri Lanka.

The hypothesis that psychometric instruments incorporating local idioms of distress predict functional impairment in a non-Western, war-affected population above and beyond translations of already established instruments was tested. Exploratory factor analysis was conducted on the War-Related Psychological and Behavioral Problems section of the Penn/RESIST/Peradeniya War Problems Questionnaire (PRPWPQ; N. Jayawickreme, Jayawickreme, Goonasekera, & Foa, 2009), a measure that incorporates local idioms of distress, using data from 197 individuals living in Northern and Eastern Sri Lanka. Three subscales--Anxiety, Depression, and Negative Perception--were identified. Regression analyses were conducted to test whether these 3 subscales better predicted functional impairment than the PTSD Symptom Scale-Self Report (PSS; Foa, Riggs, Dancu, & Rothbaum, 1993) and the Beck Depression Inventory (BDI; Beck & Steer, 1987), both widely used self-report measures of posttraumatic stress disorder and depression, respectively. Two of the 3 subscales from the PRPWPQ--Anxiety and Depression--were significantly associated with higher rates of functional impairment after controlling for age, the PSS and the BDI. After the inclusion of PRPWPQ, the PSS and the BDI did not significantly contribute to the final regression model predicting functional impairment. These findings suggest that the scores of measures with local idioms of distress have incremental validity in non-Western war-affected populations, predicting functional impairment above and beyond translations of established self-report measures that have been developed in the Western world.