The Role of Statin Therapy for Primary Prevention: What is the Evidence?

Almost one third of annual worldwide mortality is attributed to cardiovascular disease (CVD), making it the leading cause of global death. Dyslipidemia is a well-established risk factor for CVD and plays a pivotal role in the pathogenesis of atherosclerosis. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and lower low-density lipoprotein cholesterol, have emerged as the most effective therapy to date against atherothrombotic CVD. Although their role in secondary prevention of CVD is undisputed, it remains a topic for debate as to how widely they should be used for primary prevention. The Framingham Risk Score and the National Cholesterol Education Program Adult Treatment Panel III guidelines are the cornerstones for the current guidelines for primary prevention statin therapy. Although these guidelines serve as help to evaluate cardiovascular risk and effectively identify many patients who will benefit from statin therapy, there is a growing population of “intermediate-risk” patients who may be undertreated. Additional noninvasive tests may complement the traditional risk scores, potentially expanding the indications for statins.     

What is the best treatment for prediabetes?

Worldwide, along with the increasing prevalence of obesity, the number of people with prediabetes is increasing. The diagnostic criteria for prediabetes include impaired fasting glucose, impaired glucose tolerance, and metabolic syndrome. The presence of two or more of these three criteria renders a person at high risk for future diabetes. The treatment goal of prediabetes is to prevent future development of type 2 diabetes and diabetes-related cardiovascular complications. The treatment approach is twofold: glycemic control and control of cardiovascular risk factors, mainly hypertension and hyperlipidemia. Intensive lifestyle modification is the mainstay of treatment in low-risk patients. When lifestyle modification fails and in high-risk patients, medications such as metformin and/or acarbose are recommended. For high-risk patients and those who progress despite intensive lifestyle modification, thiazolidinediones are also recommended. The goals for cardiovascular risk factor control are similar to those for patients with diabetes.     

Is There a Rationale for Insulin Therapy in Pre-Diabetic Individuals?

Type 2 diabetes mellitus is usually preceded by impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), which are often referred to as pre-diabetes. Individuals with IGT demonstrate beta-cell dysfunction, insulin resistance, and increased hepatic glucose production; IGT and IFG are risk factors for both diabetes and cardiovascular disease. Type 2 diabetes is associated with micro- and macrovascular complications that lead to excessive mortality and morbidity and the risk of microvascular complications extends to people with pre-diabetes. Maintaining good glycemic control in type 2 diabetes can reduce the risk of developing chronic disease-associated complications. Most individuals who develop type 2 diabetes appear to pass through a stage of IFG or IGT; thus, early intervention (lifestyle and/or pharmacologic) in individuals with pre-diabetes may help prevent cardiovascular disease and the development of type 2 diabetes.The use of exogenous insulin treatment offers the potential to reduce the cardiovascular risk in individuals with type 2 diabetes or pre-diabetes through effective reductions in blood glucose and lipid levels, and in the associated tissue damage resulting from their chronic elevations. However, there are barriers associated with insulin initiation in both type 2 diabetes and pre-diabetes (e.g. hypoglycemia, weight gain, the possible unpredictable action of long-acting insulin, and the need for injections). Insulin glargine, with its flat time-action profile, near 24-hour duration of action, reduced risk of hypoglycemia, and improved glycemic control compared with insulin suspension isophane (neutral protamine hagedorn [NPH] insulin), may help to overcome some of these barriers.Initial results from a small study have indicated the feasibility of treating individuals with pre-diabetes to near-normoglycemia using a regimen of low-dose insulin glargine plus caloric restriction. This is being followed up in the ongoing ORIGIN (Outcomes Reduction with Initial Glargine INtervention) study, which will investigate whether treatment to near-normoglycemia with insulin glargine in individuals with IGT, IFG, or new-onset type 2 diabetes can reduce cardiovascular morbidity and mortality compared with conventional management of these conditions, and whether the rate of progression to type 2 diabetes can be similarly reduced.Further studies are needed to investigate the potential benefits of insulin therapy in individuals with pre-diabetes.     

What is a rheumatologist for?

Ask any individual rheumatologist, and I suspect that the answerwill be clear. Collectively, however, our specialty includesthe management of a diverse range of conditions ranging fromlife-threatening vasculitis, inflammatory arthritis and osteoporosisto soft tissue pain and chronic pain. In the UK, current dogmafrom the health commissioners dictates that much of this activitymight be taken away from the specialty and given to other clinicianssuch as primary care doctors and nurse or physiotherapy practitionerson the grounds of cost saving. This change in emphasis is potentiallya major threat to rheumatology as a specialty and the rheumatologistas an individual. This reflects     

What is the optimal induction strategy for older patients?

Prognoses of older patients (age ≥60 years) vary greatly following use of standard therapy, such as 3?+?7: 3 days of daunorubicin or idarubicin?+?7 days of cytarabine (ara-C). Although most older patients receive only supportive care, the principal prognostic factor among the presumably healthier treated patients is cytogenetics, with a monosomal karyotype conferring a particularly poor prognosis. However other factors are also informative and several systems incorporating multiple factors have been devised to help guide the fundamental decision as to whether a patient should receive standard therapy or, much more frequently, investigational therapy. Although physicians may be reluctant to await results of cytogenetic analysis and molecular markers (NPM, FLT3), data suggest no harm is done by waiting for these results to become available; certainly the risk of delaying therapy is less than the risk of giving a patient 3?+?7 when the risk of treatment-related mortality (TRM) is greater than the chance of a beneficial response. Nonetheless, in general the risk of TRM is less than that of resistance to therapy, even in patients aged ≥75 years. Perhaps, however, focusing on the former, there is an increasing tendency to administer azacitidine or decitabine to older patients. However there is little to suggest that on average these drugs by themselves convey what many patients would consider medically meaningful improvements in survival. Hence these drugs should not reduce the imperative of putting older patients on trials involving new drugs. Finally, confirming everyday observation, age alone is a very inadequate predictor of outcome and is likely a surrogate for other covariates. Accordingly, the common practice of assigning patients to treatment protocols based solely on age leaves much to be desired.     

What is the best surgical treatment for anorectal melanoma?

Background and aims This study compared outcome following the two common surgical procedures for anorectal melanoma: wide local excision and abdominal perineal resection. We also examined the utility of endoluminal ultrasound to guide therapy.Patients and methods Records of 19 patients surgically treated at our institution were studied. In addition to type of surgical procedure, we noted age, metastatic disease spread, sphincter involvement, tumor size and thickness, and mode of diagnosis. Survival after diagnosis and after recurrence of disease were also recorded. Ultrasound was used in seven, with the lesion delineated in six (all had therapy guided by the ultrasound). Regarding surgery ten had wide local excision, seven had abdominal perineal resection, and two had other procedures.Results The most common sites of recurrence were distant in 31.6% and regional lymph nodes in 26.3%. Mean survival after recurrence was 13 months (range 5–29). Two patients who had wide local excision are disease free and alive 135 and 29 months after diagnosis. Neither surgical treatment conferred obvious benefit on survival.Conclusion Ultrasound can guide management by delineating lesions amendable to wide local excision. Since the mortality rate is high, wide local excision offers the advantage of avoiding a permanent colostomy and should be considered the procedure of choice when excision is feasible.     

What is the definition of cure for aplastic anemia?

Treatment with immune suppression and bone marrow transplantation has improved the response rates and survival of patients with aplastic anemia. Measurement of response requires that common endpoints be recorded at specific times. There has been no agreement on such parameters for patients with aplastic anemia. In this paper issues related to measurement of response are reviewed and criteria for response are proposed. Adoption of uniform criteria would facilitate comparisons of treatment efficacy.