Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic review and individual patient data meta-analysis of randomised controlled trials.

PURPOSE: Tumour necrosis factor (TNF) plays an important role in inflammation and may affect tumour growth control. To assess the risk of malignancy with etanercept, a fusion protein that inhibits TNF action, a meta-analysis was performed using individual patient data from randomised controlled trials (RCT) in patients with rheumatoid arthritis (RA). METHODS: A search was conducted of bibliographic databases, abstracts from annual meetings and any unpublished studies on file with manufacturers of etanercept to December 2006. Only RCT of etanercept used for 12 weeks or more in patients with RA were included. Nine trials met the inclusion criteria. To adjudicate endpoints, the case narratives of potential cases were reviewed. Patient-level data were extracted from the clinical trials databases. RESULTS: The nine trials included 3316 patients, 2244 who received etanercept (contributing 2484 person-years of follow-up) and 1072 who received control therapy (1051 person-years). Malignancies were diagnosed in 26 patients in the etanercept group (incidence rate (IR) 10.47/1000 person-years) and seven patients in the control group (IR 6.66/1000 person-years). A Cox's proportional hazards, fixed-effect model stratified by trial yielded a hazard ratio of 1.84 (95% CI 0.79 to 4.28) for the etanercept group compared with the control group. CONCLUSIONS: In this analysis, the point estimate of malignancy risk was higher in etanercept-treated patients, although the results were not statistically significant. The approach of obtaining individual patient data of RCT in cooperation with trial sponsors allowed important insights into the methodological advantages and challenges of sparse adverse event data meta-analysis.

Reduced risk of cytomegalovirus infection in solid organ transplant recipients treated with sirolimus: a pooled analysis of clinical trials.

INTRODUCTION: Cytomegalovirus (CMV) is an opportunistic infection that causes substantial morbidity and mortality in transplant recipients. This pooled analysis of Wyeth clinical trials explored the incidence of CMV infection in solid organ transplant recipients treated with sirolimus versus comparator immunosuppressant drugs. METHODS: Wyeth-conducted, multicenter, randomized, comparative trials with at least one non-sirolimus-containing arm and at least 6 months' complete data were included. Cases of CMV were investigator-identified. The occurrence of CMV in sirolimus-treated patients was assessed versus all other comparator agents, versus antimetabolite agents, and versus calcineurin inhibitors. RESULTS: Nine trials in recipients of renal, liver, and cardiac transplants met the inclusion criteria; eight enrolled de novo allograft recipients, and one was a conversion trial. The primary pooled analysis revealed an odd ratio for CMV infection of 0.64 (95% confidence interval [CI] 0.42 to 1.0, P = .047) on sirolimus versus comparator immunosuppressant drugs. The subanalysis of sirolimus versus antimetabolites showed an odds ratio for CMV of 0.39 (95% CI 0.19 to 0.81, P = .012), and for sirolimus versus calcineurin inhibitors the odds ratio was 0.58 (95% CI 0.34 to 1.01, P = .054). CONCLUSION: This pooled analysis demonstrated a reduced risk of CMV infection among sirolimus-treated patients as compared to those receiving alternative forms of immunosuppression in Wyeth-sponsored clinical trials in solid organ transplantation. This risk reduction persisted in subgroup analyses stratified by class of comparator treatment.

Carotid and vertebral artery dissections.

Dissections of the carotid and vertebral arteries are a common cause of stroke in young adults. The diagnosis may be missed because the typical signs and symptoms are often delayed in onset, or easily confused with other more commonly encountered entities. Dissections of the carotid and vertebral arteries may occur spontaneously or may accompany mild to severe trauma. They present with a variety of findings including headache, neck and face pain, Horner's syndrome, or stroke.

Poisonings: food, fish, shellfish.

Not every traveler who gets sick away from home has an infection; some are poisoned. This article describes common and dangerous illnesses caused by food-borne toxins. It explores the toxic illnesses acquired from fish or seafood, including scombroid, ciguatera, pufferfish toxicity, and a variety of shellfish poisonings. It also provides a brief overview of plant toxicity. Although gastroenteritis is a common feature of many food poisonings, this article emphasizes those processes associated with neurologic manifestations, as they tend to be more dangerous to patients and less well understood by physicians. It also stresses strategies to prevent food poisoning.

Hydroxyapatite pseudopodagra in a young man: acute calcific periarthritis of the first metatarsophalangeal joint.

Pain and swelling at the first metatarsophalangeal joint can be caused by acute calcific periarthritis (ACP), an inflammatory condition resulting from deposition of hydroxyapatite crystals. A case is reported of a 23-year-old man in whom ACP was initially mistaken for gout, septic arthritis, and cellulitis. The diagnosis of ACP is based on the finding of inflammation around a joint along with radiographic evidence of periarticular soft tissue calcifications. Calcifications may disappear over time, as they did in this case. Failure to recognize this condition can lead to unnecessary testing and inappropriate treatment.

Serum tryptase in idiopathic anaphylaxis: a case report and review of the literature.

Anaphylaxis is a life-threatening disease that characteristically presents with multiple arrays of dermatologic, respiratory, cardiovascular, and gastrointestinal derangements, in general, suddenly after exposure to an allergen. It can, however, occur without an identifiable precipitant or event, and this well-defined entity has been called idiopathic anaphylaxis. The diagnosis of idiopathic anaphylaxis is made after an appropriate allergic evaluation and exclusion of a provocative trigger. We report an unusual case of manifesting with gastroenteritis, urticaria, hypotension, and syncope. Measurement of serum tryptase, a mast cell enzyme, was used to substantiate the diagnosis. Tryptase level is a useful test that can be used to help diagnose this potentially fatal disease.

Needle thoracostomy fails to detect a fatal tension pneumothorax.

Needle thoracostomy is an emergency procedure used to both diagnose and initially treat a tension pneumothorax. We report a case of fatal tension pneumothorax in an intubated patient with chronic obstructive pulmonary disease that was missed by this technique. A tension pneumothorax involving only the right middle and lower lobes was found at autopsy. The autopsy also suggested that needle thoracostomy was misleading because it sampled air from a noncommunicating bulla in the right upper lobe rather than from the pleural space. Tension physiology can exist with only localized collapse of a lung, and diagnostic needle thoracostomy can be falsely negative. When tension pneumothorax is strongly suspected, if empiric thoracentesis does not vent air under pressure, subsequent tube thoracostomy is indicated.

Splenic artery aneurysm rupture.

Splenic artery aneurysms are rare and usually asymptomatic. However, rupture can produce severe abdominal pain and prove lethal. Two cases of ruptured splenic artery aneurysm are presented. In one, cocaine injection occurred immediately prior to the onset of symptoms and may have precipitated the event.