What is the optimal therapy for young males with hypogonadotropic hypogonadism?

Hypogonadotropic hypogonadism (HH), consequent to congenital or acquired disorders of the hypothalamic–pituitary axis, presents as absent/delayed/arrested sexual maturation and infertility. Optimal management includes: (a) confirmation of the diagnosis and prognosis, (b) timing and choice of therapeutic intervention and (c) consideration of future fertility prospects. Therapy is usually initiated with testosterone to induce development of secondary sexual characteristics, taking the patient (often diagnosed late) through puberty. Monitoring of the impact of the condition on long‐term health and psychosocial function is necessary. Treatment is likely to be life‐long, requiring regular monitoring for its optimization and avoidance of adverse responses. Induction of spermatogenesis requires either pulsatile gonadotropin releasing hormone (GnRH) or gonadotropin administration. Gonadotropins can be self‐administered subcutaneously and are not inferior to the more costly GnRH. ‘Reversible genetic hypogonadotropic hypogonadism’ is a recently described entity which has implications for the long‐term management of patients with HH.     

What is the optimal medical management of ischemic heart failure?

Ischemic heart disease is an important and common contributor to the development of heart failure. Theoretically, all patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with ischemic heart disease may also theoretically benefit from the relief of ischemia, the prevention of coronary occlusion, and revascularization. However, there is little evidence to show that the presence or absence of coronary disease modifies the benefits of effective treatments such as angiotensin-converting enzyme inhibitors and beta-blockers. Moreover, there is no evidence that treatment directed specifically at myocardial ischemia or coronary disease alters outcome in patients with heart failure. Treatments aimed at relieving painless myocardial ischemia have not been shown to alter prognosis. Lipid-lowering therapy is theoretically attractive for patients with heart failure and coronary disease; however, theoretical concerns also exist about the safety of such agents, and patients with heart failure have been excluded from large outcome studies very effectively. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion seem ineffective or harmful in patients with heart failure, although warfarin may be safe and possibly effective. There is no evidence yet that revascularization improves prognosis in patients with heart failure, even in patients who are shown to have extensive myocardial hibernation. On current evidence, revascularization should be reserved for the relief of angina. Large-scale, randomized controlled trials are currently underway that are investigating the role of specific treatments targeted at coronary syndromes. The Carvedilol Hibernation Reversible Ischemia Trial: Marker of Success study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The Warfarin and Antiplatelet Therapy in Chronic Heart Failure study is comparing the efficacy of aspirin, clopidogrel, and warfarin. The Heart Revascularization Trial-United Kingdom study is assessing the effect of revascularization on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are assessing the safety and efficacy of statin therapy in patients with heart failure. Only once the outcomes to these and other planned trials are known can the medical community know how best to treat their patients.     

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.     

Medical therapy versus antireflux surgery in Barrett's esophagus: what is the best therapeutic approach?

We conducted a review of the literature comparing medical treatment with antireflux surgery in patients with Barrett's esophagus (BE). In particular, we wanted to assess the efficacy of medical and surgical therapies in preventing the progression of Barrett's epithelium to dysplasia or adenocarcinoma of the esophagus. In general, few BE patients show complete regression of BE epithelium following medical or surgical therapy. The incidence of developing dysplasia or cancer following surgical therapy appears to be less than with medical therapy; however, there is an insufficient number of current, randomized controlled studies to confirm this. Surveillance of BE is required regardless of treatment. This review suggests that there may be a trend in support of surgery being somewhat better than medical therapy in the prevention of BE progression and adenocarcinoma. We suggest that patients with BE should be considered for antireflux surgery - in particular, certain subgroups of BE patients.     

What is the medical rationale for the treatment of varicose veins?

Varicose veins occur in up to one-third of Western populations and are associated with clinical manifestations ranging from asymptomatic, isolated varicose veins (C2 disease) to venous ulceration. While the development of less invasive treatment options, such as endovenous ablation and sclerotherapy, have been well accepted by patients they have led to increased utilization of scarce health-care resources. While few would argue with the treatment of acute complications such as superficial venous thrombosis and variceal haemorrhage, the role of interventional treatment in the management of lifestyle limiting symptoms and the prevention of disease progression may be debatable. Good-quality evidence does suggest that surgical management of varicose veins is associated with improved quality of life at costs below the thresholds of many Western health-care systems. However, the progression of isolated C2 disease to advanced chronic venous insufficiency occurs infrequently and the role of treatment to prevent such progression remains undefined at present.