Safety of statins: effects on muscle and the liver

Although statin drugs can have adverse effects on muscles and the liver, these effects are uncommon. Caution is warranted in patients at higher risk, ie, those who are elderly, frail, or small; have multisystem disease; are receiving immunosuppressive drugs or other medications that interact with statins; or are receiving higher doses of a statin.     

How to use statins in patients with chronic liver disease

Clinicians may be concerned about prescribing statins to patients with chronic liver disease, but there is little evidence to suggest that drug-induced liver injury from statins is increased in these patients. Thus, we should prescribe statins for the same indications in patients with chronic liver disease as in patients without, but with closer monitoring. However, patients with acute liver disease (acute viral hepatitis, alcoholic hepatitis) should not take statins until they have recovered.     

Cataract and the use of statins: a case-control study

BACKGROUND: In animal studies, statins have induced cataract formation. Because incident cataract is relatively uncommon, studies in humans have been unable to exclude a clinically important effect. AIMS: To assess the risk of cataract associated with the use of statins, and whether it is increased by concurrent use of drugs that inhibit the cytochrome P450 system. DESIGN: Population-based case-control study. METHODS: Patients were randomly sampled from the UK General Practice Research Database. The study included 15,479 people with cataract and 15,479 controls matched for age, sex, practice and observation period. RESULTS: The crude odds ratio (OR) for the association between any recorded exposure to statins and cataract was 1.41 (95%CI 1.21-1.65), but this reduced to 1.04 (95%CI 0.89-1.23, p=0.6) after adjustment for consultation rate. There was no evidence that the risk increased with higher doses or longer duration of statin use, or that the risk varied by individual statin. There was no evidence that the risk of cataract was increased by concurrent use of statins and drugs that inhibit the cytochrome P450 system. DISCUSSION: In the short- and medium-term, statins do not seem to be associated with an increased risk of cataract. The need to assess the effects of long-term statin exposure on the eye remains.     

Risk factors for acute liver enzyme abnormalities in HIV-hepatitis B virus-coinfected patients on antiretroviral therapy

BACKGROUND: Little is known about the prognostic factors of acute liver enzyme variations in HIV-hepatitis B virus (HBV)-coinfected patients. OBJECTIVES: To identify prognostic factors of acute liver enzyme abnormalities in HIV-HBV-coinfected patients with a focus on the putative role of antiretroviral drugs. DESIGN: Data from a 3-year, prospective, multicentre cohort study involving HIV-HBV patients were used. METHODS: A Markov model was used to identify prognostic factors of acute episodes of cytolysis and cholestasis in 300 HIV-HBV-coinfected patients. The effect of antiretroviral therapy was analysed according to the classes of drugs, duration of treatment and treatment modifications. RESULTS: The incidence rates of acute episodes of cytolysis and cholestasis were 13.4 per 100 patient-years (95% confidence interval [CI] 9.5-17.3) and 7.1 per 100 patient-years (95% CI 4.2-10.0), respectively (median follow up 34.1 months). Independent risk factors for cytolysis were a high level of HBV or HIV replication, as well as a low of CD4+ T-cell count. No antiretroviral drug was associated with cytolysis, whereas protease inhibitors seemed to be independently associated with cholestasis, along with treatment modifications and the duration of HIV infection. CONCLUSION: Acute and reversible episodes of cytolysis or cholestasis were common and associated with virus- and host-related determinants. The choice of the optimal antiretroviral combination in HIV-HBV-coinfected patients must take into account the necessity of exerting an efficient control of HIV and HBV replication (associated with transient cytolysis) and the risk of inducing cholestasis (associated with the use of protease inhibitors and treatment modifications).     

Teaching an old dog new tricks: potential antiatherothrombotic use for statins

Thrombotic complications represent a highly significant component of morbidity and mortality associated with hypercholesterolemia and atherosclerosis. In this issue of the JCI, Owens et al. report possible mechanisms underlying the prothrombotic, proinflammatory state accompanying hypercholesterolemia. Using rodent, monkey, and human subjects, they show that circulating oxidized LDL and circulating monocyte-derived tissue factor are important instigating factors driving the thrombotic, inflammatory phenotype and, surprisingly, that statin therapy ameliorated the phenotype even in the absence of lowering cholesterol levels. The studies raise the intriguing possibility that therapies directed at pathways generating oxidant stress or pathways involved in transmitting oxidized LDL-mediated signals in circulating platelets and monocytes could have antiatherothrombotic potential, probably with minimal anticoagulant and hemorrhagic potential.     

Ultrasound of muscle abnormalities

Ultrasound is well suited to evaluate a wide variety of abnormalities involving skeletal muscle, including traumatic injuries, inflammatory or infectious myositis, atrophy, and tumors. Ultrasound can accurately localize and characterize a lesion, or grade the severity of injury. The unique ability of ultrasound to assess the dynamic function of muscles on the real-time or perform Doppler evaluation of vascularity provides insights that are not readily obtained with other imaging modalities. With ultrasound, image-guided biopsy can be performed in conjunction with a diagnostic evaluation. This article presents a pictorial review of lesions and abnormalities involving skeletal muscles, and discusses characteristic findings, classifications, and imaging methods.     

Comparison of reports from patients and health professionals: statins and muscle disorders

BACKGROUND AND METHODS: Statin- and especially cerivastatin-induced muscle effects reported by patients and doctors to the Limoges centre of pharmacovigilance during the years 2000 and 2001 were compared. In both instances, only reports with complaints of muscle pain or modification of creatine phospokinase (CPK) values and cases with one statin or one statin-fibrate association were selected. RESULTS: In the reports of 28 patients (21 involving cerivastatin), 80 % of the patients complained of diffuse myalgia. The dose was normal. The CPK value (six cases) was 1.7 +/- 0.9 N (upper limit of normal) [1-3.2 N]. Thirteen medical reports were received at the pharmacovigilance centre during the years 2000 and 2001: eight myalgias and five increases in CPK without muscle pain (9 +/- 9 N [1-20 N]). No common cases were identified among patients' and doctors' reports. Doctors tended to declare more severe effects, not necessarily associated with clinical signs. Patients' reports were at times inaccurate. CONCLUSION: Before including patients' reports in the present pharmacovigilance database, a thorough reconsideration is necessary.     

他汀类药物致肝损伤的临床特征及其防治

他汀类药物因其抗炎、调脂的作用目前被广泛用于动脉粥样硬化性疾病,尤其是心脑血管病的一级和二级预防中。然而,其相关不良反应如肌病、横纹肌溶解、肝损伤等屡见报道。本文就他汀类药物致肝损伤的特点、发病机制、监测以及处理等方面做一综述。     

Echo-guided percutaneous puncture: A safe and valuable therapeutic tool for amebic liver abscess

To clarify the therapeutic role of echo-guided percutaneous puncture (EPP) in management of amebic liver abscess, 20 patients (24 abscesses) received metronidazole plus EPP. Fluid was aspirated through Chiba needles under real-time sonographic guidance so as to reduce cavity size to less than 3 cm. Not more than two EPPs were necessary in the majority of cases and no complication followed the procedure.This scheme resulted in a shortening of time of both hospitalization (20 days) and liver lesion healing as assessed by ultrasound (4 months).It is concluded that EPP is a valuable and safe therapeutic tool for hepatic amebic abscess.     

High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial

BACKGROUND: Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle. METHODS: Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up. RESULTS: The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin. CONCLUSIONS: High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.     

超声诊断胎儿肝脏膨出畸形1例

孕妇,30岁,足月待产,B超检查了解胎儿情况.超声所见:子宫增大,宫腔内见胎儿结构声像,胎头位于下腹部,颅骨光环完整,双顶径90 mm,脑中线清晰,居中.四肢发育正常,脊柱排列整齐,胎心、胎动良好,腹壁不完整,可见一 33 mm的缺损,从缺损口凸出一类球形的中等回声团块,大小38 mm×41 mm×32 mm,其内部回声均匀.超声诊断(见图):①宫内妊娠,单活胎;②胎儿畸形(内脏膨出);③羊水过多.次日引产一男婴,脐部向外突出一球形包块.尸检:包块表面为胎儿皮肤层,切开包块,内为肝脏组织,脐区肌层、脂肪组织缺如.为先天性肝脏膨出畸形,与产前超声检查基本符合.     

Promoting safe use of medical devices

Although patient safety initiatives in the clinical environment have focused primarily on medication errors to date, medical devices also contribute significantly to patient injuries and deaths. This article addresses the Food and Drug Administration's (FDA) efforts to promote safe use of medical devices by nurses at the point of care. The nurses with whom we have discussed the effects of medical devices, and also those surveyed by the medical device industry and professional nursing associations, are concerned about the profound effects, both desired and undesired, that medical devices have on patient outcomes. We believe that professional nurses, individually and through their professional associations, can help address these concerns by becoming aware of how to share their observations with the FDA and by working with their professional associations to develop position statements that focus on achieving safe and desired patient outcomes. In this article we will identify factors contributing to adverse events related to medical devices, address the need for more medical device adverse-event reporting, describe position statements that have already been made by some professional associations, and share insights regarding future directions along with ideas for educating staff to use medical devices safely.     

Narcotic use in the hospital: reasonably safe?

OBJECTIVE: To determine the causes and frequency of overdoses associated with the administration of opioid analgesics in hospitalized patients. DESIGN: Case series. SETTING: Two acute care teaching hospitals. PATIENTS: Eighty-one hospitalized patients who received naloxone for a clinically suspected narcotic overdose. INTERVENTIONS: Three investigators reviewed each patient who received naloxone during a 12-month period. The patients were judged to have a narcotic overdose if caregivers documented an immediate improvement in mental status, respiratory rate, or blood pressure after naloxone administration. MAIN OUTCOME MEASURES: The number and causes of narcotic overdoses were determined. The frequency of morphine and meperidine overdoses was calculated. The number of incidents reported using incident or adverse drug reaction reports or the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. RESULTS: In the 22 overdoses that occurred, 14 (64 percent) were caused by medication prescribing, compounding, or administration errors and potentially were preventable. The remaining eight patients experienced an overdose despite receiving appropriate amounts of opioids. The frequency of overdoses was 0.4 and 0.2 percent of total patients receiving morphine or meperidine, respectively, at the two hospitals. Nonreporting of these narcotic overdoses was frequent. In one hospital, 1 incident report and 3 adverse drug reactions were reported for 17 overdoses. At the second hospital, 1 incident report and 1 adverse drug reaction were reported for 6 overdoses. None of the patient charts included an ICD-9-CM code that documented the problem. CONCLUSIONS: The causes of overdoses are not limited to prescribing and administration errors. Some patients, despite proper execution of appropriate orders, develop a narcotic overdose. Caregivers must be aware of this problem and monitor patients for a decrease in mental status and respiratory rate. In addition, we conclude that an important number of hospitalized patients develop an overdose even though the frequency is low related to the number of patients receiving narcotics.     

Effective use of statins to prevent coronary heart disease

Primary and secondary prevention trials have shown that use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) to lower an elevated low-density lipoprotein cholesterol level can substantially reduce coronary events and death from coronary heart disease. In 1987 and 1993, the National Cholesterol Education Program promulgated guidelines for cholesterol screening and treatment. Thus far, however, primary care physicians have inadequately adopted these guidelines in clinical practice. A 1991 study found that cholesterol screening was performed in only 23 percent of patients. Consequently, many patients with elevated low-density lipoprotein levels and a high risk of primary or recurrent ischemic events remain unidentified and untreated. A study published in 1998 found that fewer than 15 percent of patients with known coronary heart disease have low-density lipoprotein levels at the recommended level of below 100 mg per dL (2.60 mmol per L). By identifying patients with elevated low-density lipoprotein levels and instituting appropriate lipid-lowering therapy, family physicians could help prevent cardiovascular events and death in many of their patients.