Recognizing and improving patient nonadherence to statin therapy

Despite landmark trials demonstrating the benefits of statin therapy for lipid lowering and in the primary and secondary prevention of acute coronary events, many patients do not adhere to medication regimens. Although incremental gains have been made in lowering the absolute levels of total serum cholesterol in the general population, only one third of treated patients are achieving their lipid goals, with fewer than 20% of patients with cardiovascular disease at their target lipid goals. Only half of patients continue taking statins prescribed to them at 6 months, and only 30% to 40% continue taking them at 1 year. Predictors of poor adherence to statins are described, such as female gender and low socioeconomic status. Approaches that are physician focused and patient centered, such as frequent follow-up and serum lipid testing and better education of patients about cardiovascular disease, are suggested to offset a major impediment to achieving the full therapeutic outcomes promised by clinical trials.     

Association between alcohol consumption and both osteoporotic fracture and bone density

Objective

Alcoholism is a risk factor for osteoporotic fractures and low bone density, but the effects of moderate alcohol consumption on bone are unknown. We performed a systematic review and meta-analysis to assess the associations between alcohol consumption and osteoporotic fractures, bone density and bone density loss over time, bone response to estrogen replacement, and bone remodeling.

Methods

MEDLINE, Current Contents, PsychINFO, and Cochrane Libraries were searched for studies published before May 14, 2007. We assessed quality using the internal validity criteria of the US Preventive Services Task Force.

Results

We pooled effect sizes for 2 specific outcomes (hip fracture and bone density) and synthesized data qualitatively for 4 outcomes (non-hip fracture, bone density loss over time, bone response to estrogen replacement, and bone remodeling). Compared with abstainers, persons consuming from more than 0.5 to 1.0 drinks per day had lower hip fracture risk (relative risk = 0.80 [95% confidence interval, 0.71-0.91]), and persons consuming more than 2 drinks per day had higher risk (relative risk = 1.39 [95% confidence interval, 1.08-1.79]). A linear relationship existed between femoral neck bone density and alcohol consumption. Because studies often combined moderate and heavier drinkers in a single category, we could not assess relative associations between alcohol consumption and bone density in moderate compared with heavy drinkers.

Conclusion

Compared with abstainers and heavier drinkers, persons who consume 0.5 to 1.0 drink per day have a lower risk of hip fracture. Although available evidence suggests a favorable effect of alcohol consumption on bone density, a precise range of beneficial alcohol consumption cannot be determined.     

Unilateral pupillary mydriasis from nebulized ipratropium bromide: A false sign of brain herniation in the intensive care unit

Although there are many causes of anisocoria in the intensive care setting, the development of unilateral mydriasis in patients with intracranial hemorrhage or tumor is a neurological emergency, as it may herald the onset of uncal herniation. We describe two patients with a hemiparesis from neurosurgical disorder who subsequently developed a fixed and dilated pupil. The pupillary abnormality was caused by nebulized ipratropium bromide in both cases, and resolved when the medication was discontinued. Nebulized ipratropium may leak from the mask into ipsilateral eye and cause mydriasis in patients with facial weakness. This benign cause of anisocoria in the intensive care setting is distinguished from uncal herniation by the laterality of neurologic findings, and lack of mental status change, ptosis, and extraocular movement impairment.     

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study

CytoSorb^® (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb^® in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb^® hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock.     

Ubiquitin-proteasomal degradation of COX-2 in TGF-β stimulated human endometrial cells is mediated through endoplasmic reticulum mannosidase I

Cyclooxygenase (COX)-2 is a key regulatory enzyme in the production of prostaglandins (PG) during various physiological processes. Mechanisms of COX-2 regulation in human endometrial stromal cells (human endometrial stromal cells) are not fully understood. In this study, we investigate the role of TGF-β in the regulation of COX-2 in human uterine stromal cells. Each TGF-β isoform decreases COX-2 protein level in human uterine stromal cells in Smad2/3-dependent manner. The decrease in COX-2 is accompanied by a decrease in PG synthesis. Knockdown of Smad4 using specific small interfering RNA prevents the decrease in COX-2 protein, confirming that Smad pathway is implicated in the regulation of COX-2 expression in human endometrial stromal cells. Pretreatment with 26S proteasome inhibitor, MG132, significantly restores COX-2 protein and PG synthesis, indicating that COX-2 undergoes proteasomal degradation in the presence of TGF-β. In addition, each TGF-β isoform up-regulates endoplasmic reticulum (ER)-mannosidase I (ERManI) implying that COX-2 degradation is mediated through ER-associated degradation pathway in these cells. Furthermore, inhibition of ERManI activity using the mannosidase inhibitor (kifunensine), or small interfering RNA-mediated knockdown of ERManI, prevents TGF-β-induced COX-2 degradation. Taken together, these studies suggest that TGF-β promotes COX-2 degradation in a Smad-dependent manner by up-regulating the expression of ERManI and thereby enhancing ER-associated degradation and proteasomal degradation pathways.     

Bleeding-avoidance strategies and outcomes in patients ≥80 years of age with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the NCDR CathPCI Registry)

The purpose of our study was to evaluate the use of bleeding-avoidance strategies (BAS) and risk-adjusted bleeding over time in patients ≥80 years of age undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. We analyzed data from the CathPCI Registry from July 1, 2006 through June 30, 2009. Patients were included if they were ≥80 years old, presented with ST-segment elevation myocardial infarction, and underwent primary PCI. We evaluated trends in use of BAS (direct thrombin inhibitors, vascular closure devices, and radial access) and risk-adjusted bleeding over time. Of 10,469 patients ≥80 years old undergoing primary PCI, 1,002, (9.6%) developed a bleeding complication. Use of direct thrombin inhibitors and vascular closure devices increased over time (12.8% to 24.9% and 29.2% to 32.7%, p <0.01 and <0.05 for trends, respectively). Radial access was extremely uncommon (<1%) and did not change over the course of the study. In multivariable analyses, use of BAS was associated with lower bleeding. However, over the course of the study period, overall risk-adjusted bleeding did not decrease significantly (9.9% to 9.4%, p = 0.14 for trend). In conclusion, patients ≥80 years old undergoing primary PCI are at high risk of bleeding, and despite significant increases in use of BAS, the overall rate of bleeding complications remains high.     

Thymosin β4 and Cardiac Regeneration: Are We Missing a Beat?

Epicardial resident stem cells are known to differentiate into cardiomyocytes during cardiac development, amongst other cell types. Whether epicardium-derived progenitor cells (EPDCs) retain this plasticity in the adult heart has been the topic of heated scientific debate. Priming with thymosin beta 4, a peptide which has been suggested to be critical for cardiac development and to have cardio-protective properties, was recently shown to induce differentiation of EPDCs into cardiomyocytes in a small animal model of myocardial infarction. This finding is in stark contrast to another recent study in which thymosin beta 4 treatment following myocardial infarction did not induce cardiomyocyte differentiation of EPDCs. While EPDCs seem to exhibit overall cardio-protective effects on the heart following myocardial infarction, they have not been shown to differentiate into cardiomyocytes in a clinically relevant setting. It will be important to understand why the ability of one therapeutic agent to induce cardiomyocyte differentiation of EPDCs seemingly depends on a single variable, i.e. the time of administration. Furthermore, in light of a recent report, it appears that thymosin beta 4 may be dispensable for cardiac development.