Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial.

BACKGROUND: Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. METHODS: Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. FINDINGS: Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was -5·2 (95% CI -5·88 to -4·72) after vertebroplasty and -2·7 (-3·22 to -1·98) after conservative treatment, and between baseline and 1 year was -5·7 (-6·22 to -4·98) after vertebroplasty and -3·7 (-4·35 to -3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74-3·37, p<0·0001) at 1 month and 2·0 (1·13-2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. INTERPRETATION: In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. FUNDING: ZonMw; COOK Medical.

Addison's Disease Caused by Tuberculosis: Diagnostic and Therapeutic Difficulties.

OBJECTIVES: To demonstrate difficulties in diagnosing and treating Addison's disease caused by tuberculosis. MATERIALS AND METHODS: We present a clinical case and review of the literature. RESULTS: A 62-year-old man presented with gastrointestinal symptoms, weight loss and enlarged adrenal glands. After 2 months of diagnostic tests, a working diagnosis of Addison's disease due to extrapulmonary tuberculosis was made. Treatment was challenging due to interaction between rifampicin and steroids. CONCLUSION: Our case illustrates that in non-endemic countries, extrapulmonary tuberculosis still needs to be considered as a possible cause of Addison's disease. LEARNING POINTS: In non-endemic countries, extrapulmonary tuberculosis still needs to be considered as a possible cause of Addison's disease.Treating tuberculosis and adrenal cortex insufficiency can be challenging because of the interaction between rifampicin and adrenocorticoid drugs.Adrenal function does not recover in most cases of Addison's disease caused by tuberculosis.

Pharmacological therapy for acromegaly: a critical review.

The treatment of acromegaly has changed considerably over the last few decades. In the late 1970s, the introduction of the dopamine receptor agonists made it possible to reduce growth hormone (GH) secretion by somatotropinomas for the first time. Thereafter, the introduction of the somatostatin analogues in the early 1980s had major implications. Recently, the first data on the use of genetically engineered human GH receptor (GHR) antagonists that block GH actions have become available. These GHR antagonists reduce both the biochemical abnormalities of acromegaly, as well as improve clinical signs and symptomatology. In this article we firstly review available data on dopamine agonists. Currently these compounds should be considered in patients with a mixed GH-prolactin secreting pituitary adenoma and/or those in whom pre-treatment insulin-like growth factor (IGF)-I concentrations are below 750 microg/L. We then discuss the somatostatin analogues. These compounds are capable of achieving biochemical control of GH and IGF-I in 50-60% of patients and tumour shrinkage in some 30%. In particular, candidates for treatment with these compounds are those patients who have undergone an unsuccessful transsphenoidal operation or who await the therapeutic effect of external pituitary irradiation. In selected patients primary medical therapy with somatostatin analogues is certainly a feasible option. To date, pegvisomant is the only available member of a new class of drugs that was especially designed to block the GHR. Pegvisomant is the most effective treatment for normalising IGF-I concentrations and appears to have a good safety profile. However, liver function tests should be regularly monitored and tumour size should be closely followed. Finally, we propose a treatment algorithm for acromegaly.

Ghrelin drives GH secretion during fasting in man.

OBJECTIVES: In humans, fasting leads to elevated serum GH concentrations. Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin release are considered as the main mechanisms that induce this elevated GH secretion during fasting. Ghrelin is an endogenous ligand of the GH secretagogue receptor and is synthesized in the stomach. As ghrelin administration in man stimulates GH release, while serum ghrelin concentrations are elevated during fasting in man, this increase in ghrelin levels might be another mechanism whereby fasting results in stimulation of GH release. DESIGN AND SUBJECTS: In ten healthy non-obese males we performed a double-blind placebo-controlled crossover study comparing fasting with and fasting without GH receptor blockade. GH, ghrelin, insulin, glucose and free fatty acids were assessed. RESULTS: While ghrelin levels do not vary considerably in the fed state, fasting rapidly induced a diurnal rhythm in ghrelin concentrations. These changes in serum ghrelin concentrations during fasting were followed by similar, profound changes in serum GH levels. The rapid development of a diurnal ghrelin rhythm could not be explained by changes in insulin, glucose, or free fatty acid levels. Compared with fasting without pegvisomant, fasting with pegvisomant did not change the ghrelin rhythm. CONCLUSIONS: These data indicate that ghrelin is the main driving force behind the enhanced GH secretion during fasting.

Insights from growth hormone receptor blockade.

Pegvisomant is a genetically manipulated growth hormone (GH) that disables signal transduction through the GH receptor and thus functions as a GH receptor antagonist. In a series of studies of the metabolic effects of GH in healthy male individuals, pegvisomant has been used to create a model of acute GH deficiency but without the typical alterations in body composition. This review summarizes studies of the effects of GH receptor blockade and fasting, either alone or in combination, on determinants of GH release. Based on these and other data we present a model to explain the somatotroph hyperactivity of fasting

[Domperidone and the risk of sudden cardiac death]. / Domperidon en het risico op acute hartdood.

Domperidone is an antiemetic drug with relatively few side-effects. In the Netherlands, domperidone is available over the counter. Recently, discussion on the safety of domperidone has arisen because an association with sudden cardiac death has been suggested. We performed a systematic literature search to investigate whether these concerns can be justified. Three out of four case-control studies found statistically significant increased odds ratios for sudden cardiac death when using domperidone. A dose-response relationship was described in one study. Results may be influenced by several confounders. We conclude that there is a relationship between domperidone use and sudden cardiac death at doses of more than 30 mg per day. We recommend that the indication be weighed up properly, that domperidone be provided only on prescription, and dose advice be given. At a dose of 30 mg per day, domperidone can be prescribed safely.

Surgical treatment of obesity.

More than half of the European population are overweight (body mass index (BMI) > 25 and < 30 kg/m2) and up to 30% are obese (BMI > or = 30 kg/m2). Being overweight and obesity are becoming endemic, particularly because of increasing nourishment and a decrease in physical exercise. Insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cholelithiasis, certain forms of cancer, steatosis hepatis, gastroesophageal reflux, obstructive sleep apnea, degenerative joint disease, gout, lower back pain, and polycystic ovary syndrome are all associated with overweight and obesity. The endemic extent of overweight and obesity with its associated comorbidities has led to the development of therapies aimed at weight loss. The long-term effects of diet, exercise, and medical therapy on weight are relatively poor. With respect to durable weight reduction, bariatric surgery is the most effective long-term treatment for obesity with the greatest chances for amelioration and even resolution of obesity-associated complications. Recent evidence shows that bariatric surgery for severe obesity is associated with decreased overall mortality. However, serious complications can occur and therefore a careful selection of patients is of utmost importance. Bariatric surgery should at least be considered for all patients with a BMI of more than 40 kg/m2 and for those with a BMI of more than 35 kg/m2 with concomitant obesity-related conditions after failure of conventional treatment. The importance of weight loss and results of conventional treatment will be discussed first. Currently used operative treatments for obesity and their effectiveness and complications are described. Proposed criteria for bariatric surgery are given. Also, some attention is devoted to more basic insights that bariatric surgery has provided. Finally we deal with unsolved questions and future directions for research.