Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase

Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms

The diagnosis and management of neuropathic pain in daily practice in Belgium: an observational study

<p>Abstract</p> <p>Background</p> <p>This open, multicentre, observational survey investigated how physicians diagnose neuropathic pain (NeP) by applying the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, and how neuropathic pain conditions are managed in daily practice in Belgium.</p> <p>Methods</p> <p>Physicians were asked to complete the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale for diagnosing NeP, and to fill out a questionnaire regarding the management of NeP, together with a questionnaire evaluating the impact of pain on sleep and daily life. Data on 2,480 pain patients were obtained. A LANSS score ≥ 12 (meaning NeP is most probably present) was reported for 1,163 patients. Pathologies typically associated with NeP scored above 12 on the LANSS scale, contrary to pathologies generally considered as being of non-neuropathic origin.</p> <p>Results</p> <p>Over 90% of the patients with a LANSS score ≥ 12 reported that the pain impaired sleep. A high impact on social, family and professional life was also recorded. Additional examinations were performed in 89% of these patients. Most patients were taking multiple drugs, mainly paracetamol and non-steroidal anti-inflammatory drugs, indicating that physicians generally tend to follow treatment guidelines of chronic nociceptive pain, rather than the specific ones for NeP. Specific neuropathic guidelines rather recommend the use of anti-epileptic drugs, tricyclic antidepressants or weak opioids as first-line treatment.</p> <p>Conclusion</p> <p>In our survey, application of the LANSS scale lead to pronounced treatment simplification with fewer drug combinations. Awareness about NeP as well as its specific treatment recommendations should be raised among healthcare providers. We concluded that the LANSS screening scale is an interesting tool to assist physicians in detecting NeP patients in routine clinical care.</p

Patient involvement in medical decision-making and pain among elders: physician or patient-driven?

BACKGROUND: Pain is highly prevalent among older adults, but little is known about how patient involvement in medical decision-making may play a role in limiting its occurrence or severity. The purpose of this study was to evaluate whether physician-driven and patient-driven participation in decision-making were associated with the odds of frequent and severe pain. METHODS: A cross-sectional population-based survey of 3,135 persons age 65 and older was conducted in the 108-county region comprising West Texas. The survey included self-reports of frequent pain and, among those with frequent pain, the severity of pain. RESULTS: Findings from multivariate logistic regression analyses showed that higher patient-driven participation in decision-making was associated with lower odds (OR, 0.82; 95% CI, 0.75–0.89) of frequent pain, but was not significantly associated with severe pain. Physician-driven participation was not significantly associated with frequent or severe pain. CONCLUSIONS: The findings suggest that patients may need to initiate involvement in medical decision-making to reduce their chances of experiencing frequent pain. Changes to other modifiable health care characteristics, including access to a personal doctor and health insurance coverage, may be more conducive to limiting the risk of severe pain

Predictors of Occurrence and Severity of First Time Low Back Pain Episodes: Findings from a Military Inception Cohort

Primary prevention studies suggest that additional research on identifying risk factors predictive of low back pain (LBP) is necessary before additional interventions can be developed. In the current study we assembled a large military cohort that was initially free of LBP and followed over 2 years. The purposes of this study were to identify baseline variables from demographic, socioeconomic, general health, and psychological domains that were predictive of a) occurrence; b) time; and c) severity for first episode of self-reported LBP. Baseline and outcome measures were collected via web-based surveillance system or phone to capture monthly information over 2 years. The assembled cohort consisted of 1230 Soldiers who provided self-report data with 518 (42.1%) reporting at least one episode of LBP over 2 years. Multivariate logistic regression analysis indicated that gender, active duty status, mental and physical health scores were significant predictors of LBP. Cox regression revealed that the time to first episode of LBP was significantly shorter for Soldiers that were female, active duty, reported previous injury, and had increased BMI. Multivariate linear regression analysis investigated severity of the first episode by identifying baseline predictors of pain intensity, disability, and psychological distress. Education level and physical fitness were consistent predictors of pain intensity, while gender, smoking status, and previous injury status were predictors of disability. Gender, smoking status, physical health scores, and beliefs of back pain were consistent predictors of psychological distress. These results provide additional data to confirm the multi-factorial nature of LBP and suggest future preventative interventions focus on multi-modal approaches that target modifiable risk factors specific to the population of interest

Women performing repetitive work: Is there a difference in the prevalence of shoulder pain and pathology in supermarket cashiers compared to the general female population?

Objectives: Shoulder disorders in the occupational environment have been widely studied, but the quality of research and methodology applied vary. Little has been done to ascertain whether shoulder pain in female repetitive workers is due to any verifiable pathology, or to compare findings with the general population. Therefore, we decided to evaluate the prevalence of self-reported shoulder pain in a group of female supermarket cashiers and in the general female population using a standardized questionnaire. Shoulder pain prevalence was then compared to imaging findings in order to assess specific and non-specific pain prevalence. Material and Methods: 196 cashiers and 302 controls filled in a standardized shoulder questionnaire and underwent an imaging examination of a shoulder. Results: The prevalence of shoulder pain was significantly higher in the group of cashiers (46.4%) than in the general population (25.5%) (OR = 1.821; 95% CI: 1.426–2.325). Specific pain prevalence was higher among the controls (19.5%) than among the cashiers (13.2%). Conclusions: The more frequent reports of shoulder pain in the supermarket cashiers are not correlated with a higher prevalence of imaging abnormalities. The causes of these more frequent complaints should be probably sought in the psycho-social and occupational environment