Rivaroxaban for thromboprophylaxis among patients recently hospitalized for acute infectious diseases: a subgroup analysis of the MAGELLAN study.

Essentials Net benefit of venous thromboprophylaxis (VTE) in patients hospitalized for infections is unknown. MAGELLAN trial subgroup analysis was performed for patients hospitalized for acute infectious diseases. At day 35, prolonged rivaroxaban prophylaxis reduced VTE compared to enoxaparin (4.2% vs. 6.6%). Rivaroxaban prophylaxis reduced VTE in patients hospitalized for active lung infections. SUMMARY: Background Despite the well-established association between infection and venous thromboembolism (VTE), there are few data specifically assessing the efficacy and safety of the VTE prophylaxis strategies for patients hospitalized for acute infectious diseases. Objectives To estimate the incidence of VTE and bleeding outcomes, comparing prolonged prophylaxis with rivaroxaban 10 mg daily for 35 days with enoxaparin 40 mg daily for 10 days. Patients/Methods A subgroup analysis of patients hospitalized for acute infectious diseases in the MAGELLAN trial was performed. The primary efficacy outcome was the composite of asymptomatic proximal or symptomatic VTE at days 10 and 35. The principal safety outcome was the composite of major or clinically relevant non-major bleeding. Results Three thousand one hundred and seventy-three patients with acute infectious diseases leading to hospitalization were randomized to either rivaroxaban (n = 1585) or enoxaparin/placebo (n = 1588), and received at least one dose of study medication. At day 10, primary composite efficacy outcomes did not differ between prophylaxis strategies (rivaroxaban, 2.7%; and enoxaparin, 3.7%). At day 35, there were fewer VTE events with rivaroxaban (4.2%) than with enoxaparin (6.6%) (relative risk [RR] 0.64; 95% confidence interval [CI] 0.45-0.92). Patients with pulmonary infections randomized to rivaroxaban had a lower incidence of VTE both at 10 days (RR 0.50, 95% CI 0.28-0.90) and at 35 days (RR 0.54, 95% CI 0.33-0.87). Primary safety outcome events were increased with rivaroxaban (RR 2.42, 95% CI 1.60-3.66). Conclusions Prolonged rivaroxaban prophylaxis reduced the incidence of VTE in patients hospitalized for acute infectious diseases, particularly those involving the lungs. Efficacy benefits were, in part, offset by bleeding outcomes. ClinicalTrials.gov Number: NCT 00571649.

D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial.

BACKGROUND: D-dimer concentrations have not been evaluated extensively as a predictor of increased venous thromboembolism (VTE) risk in acutely ill, hospitalized medical patients. OBJECTIVES: To analyze the relationships between D-dimer concentration, VTE and bleeding in the MAGELLAN trial (NCT00571649). PATIENTS/METHODS: This was a multicenter, randomized, controlled trial. Patients aged ≥ 40 years, hospitalized for acute medical illnesses with risk factors for VTE received subcutaneous enoxaparin 40 mg once daily for 10 ± 4 days then placebo up to day 35, or oral rivaroxaban 10 mg once daily for 35 ± 4 days. Patients (n = 7581) were grouped by baseline D-dimer ≤ 2 × or > 2 × the upper limit of normal. VTE and major plus non-major clinically relevant bleeding were recorded at day 10, day 35, and between days 11 and 35. RESULTS: The frequency of VTE was 3.5-fold greater in patients with high D-dimer concentrations. Multivariate analysis showed that D-dimer was an independent predictor of the risk of VTE (odds ratio 2.29 [95% confidence interval 1.75-2.98]), and had a similar association to established risk factors for VTE, for example cancer and advanced age. In the high D-dimer group, rivaroxaban was non-inferior to enoxaparin at day 10 and, unlike the low D-dimer group, superior to placebo at day 35 (P < 0.001) and days 11-35 (P < 0.001). In both groups, bleeding outcomes favored enoxaparin/placebo. CONCLUSIONS: Elevated baseline D-dimer concentrations may identify acutely ill, hospitalized medical patients at high risk of VTE for whom extended anticoagulant prophylaxis may provide greater benefit than for those with low D-dimer concentrations.

Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction.

BACKGROUND: This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation of metoprolol, metoprolol succinate (CR/XL). METHODS AND RESULTS: Sixty patients were randomly assigned with a 2:1 ratio, drug versus placebo, administered with a gradually increasing dose of 12.5 to 150 mg of blinded medication during an 8-week period and continued for 6 months. The average peak dose achieved was 99 mg and 132 mg in the metoprolol succinate and placebo groups, respectively. The drug was well tolerated and there was no significant difference in drug withdrawals, New York Heart Association class, or quality of life assessment. The increase in left ventricular ejection fraction measure at baseline and 6 months measured by radioisotopic ventriculography was greater in the metoprolol succinate group (27. 5% to 36.3%) than in the placebo group (26% to 27.9%) (P <.015). Examination of serial Holter electrocardiographic recordings indicate that metoprolol succinate therapy was associated with a significant (P <.05) decrease in total ventricular ectopy at 8 weeks of therapy and a decrease in ventricular couplets and nonsustained ventricular tachycardia at 8 through 26 weeks of therapy. No changes were observed in plasma norepinephrine during therapy except a transitory significant (P <.05) increase in N terminal proatrial natriuretic factor at 8 weeks in the metoprolol succinate group. CONCLUSIONS: This study indicates that treatment with metoprolol succinate for a 6-month period is safe and well tolerated and is associated with an increase in left ventricular ejection fraction and a decrease in ventricular ectopic beats.

Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group.

BACKGROUND & AIMS: Budesonide is a highly potent topical glucocorticosteroid that is characterized by low systemic availability as a result of high first-pass hepatic metabolism. The aim of this study was to evaluate the efficacy and safety of three doses of an enema preparation of budesonide in patients with active distal ulcerative colitis/proctitis. METHODS: In a double-blind multicenter trial, 233 patients were randomized to receive either a placebo enema or budesonide enema at a dose of 0.5 mg/100 mL, 2.0 mg/100 mL, or 8.0 mg/100 mL. The primary efficacy variables were an improvement of sigmoidoscopic inflammation grade, total histopathology score, and remission rates. Effects on cortisol concentrations were also assessed. RESULTS: After 6 weeks of treatment, there was significant improvement in sigmoidoscopy and histopathology scores in the budesonide 2.0-mg and 8.0-mg dose groups compared with placebo. Remission was achieved in 19% of patients in the 2.0-mg budesonide group (P

Sexual violence in women's lives. Findings from the Women's Safety Project, a community-based survey.

PIP: This paper presents a community-based study, which aims to determine the interconnections between women's experiences of sexual abuse in childhood, sexual assault in adulthood, and physical assault in intimate relationships in Toronto, Canada. An in-depth face-to-face interview was conducted with 420 women who comprised the random sample of the women living in Toronto, Canada. Findings on the prevalence and effects of various forms of sexual abuse and violence revealed that 97.6% of the woman interviewed reported that they personally experienced some form of sexual violation. Sexual abuse in childhood (including incest), sexual assault, sexual harassment, and physical assault in intimate relationships were documented. Among the findings were that one-fourth of the women in the sample were physically assaulted by a male intimate, one-half of the women reported being raped or almost raped, and nearly half of the respondents reported experiencing some kind of sexual abuse before reaching age 16.^ieng

Isolated erythroid hypoplasia and renal insufficiency induced by long-term griseofulvin therapy.

We describe a patient with hematuria, pyuria, eosinophiluria, decreased renal function, and severe anemia that developed while she was receiving chronic therapy with griseofulvin for onychomycosis. We offer evidence that griseofulvin can cause an isolated erythroid hypoplasia and possibly an allergic interstitial nephritis. This is the first documented case of the above entities induced by the agent. We would recommend, based on our report, that otherwise healthy patients, when maintained on the drug for extended periods of time, have periodic determinations of renal function and hematologic status. As drug-induced erythroid hypoplasia typically occurs after a relatively long period of dosing, it may be prudent in certain individuals to monitor the CBC at approximately bimonthly intervals after initiation of therapy. Recommendations regarding monitoring of renal function are more difficult, as acute allergic interstitial nephritis can occur after either short- or long-term exposure to certain drugs.

Disseminated toxoplasmosis presenting as symptomatic orchitis and nephrotic syndrome.

Toxoplasma gondii is a common pathogen in patients with acquired immune deficiency syndrome (AIDS). The most common modes of presentation are related to the central nervous system (CNS), usually with headache, fever, and focal neurological signs. Extra-neural manifestations are unusual in patients with AIDS. The authors present a patient with AIDS who had disseminated toxoplasmosis whose initial clinical presentation was symptomatic orchitis and the nephrotic syndrome (NS). Testicular involvement with toxoplasmosis has been described only rarely, predominantly as an incidental finding at autopsy. Toxoplasmosis is a rare cause of nephrotic syndrome, with the majority of cases associated with congenital infection. In this case, the nephrotic syndrome remitted only after orchiectomy and chemotherapy for toxoplasmosis, but recurred when the patient had a relapse of his CNS disease. Toxoplasmosis in AIDS may present with extra-neural manifestations and may be an etiologic agent for NS in some patients with AIDS.

Lymphoedema due to lymphatic hyperplasia: a case report.

An unusual case of generalised lymphoedema is described. The congenital nature of the lymphatic anomaly and the significance of its lymphographic appearance are discussed.

The ultrasound spectrum of emphysematous cholecystitis.

This report presents a gamut of ultrasound signs that may be seen in emphysematous cholecystitis. These can be summarized as follows: Intraluminal gas: (a) A dense band of hyper-reflective echoes with distal reverberations when gallbladder is full of gas. (b) A band of reverberations in the gas-filled portion of the gallbladder with the usual signs of cholecystitis in the bile-filled portion when the gallbladder is partially full of gas. Intramural gas: (c) An area of high reflectivity in the gallbladder wall with reverberations that may change position with change in position of patient. (d) A bright hyper-reflective ring emanating from the whole circumference of the gallbladder.

Polyarteritis nodosa and familial Mediterranean fever: a report of 2 cases and review of the literature.

Two cases of polyarteritis nodosa (PAN) in patients with familial Mediterranean fever (FMF) are reported. These and another 11 cases found in the literature suggest that PAN occurs more commonly in patients with FMF than would be expected in the general population. Perirenal hematoma, which is surprisingly high in patients with FMF, is a life threatening complication of PAN. The diagnosis of PAN in patients with FMF may be delayed due to the similarity of the clinical manifestations of both diseases.

HLA associations in heroin-associated nephropathy.

Heroin-associated nephropathy (HAN) occurs almost exclusively in black heroin abusers, suggesting a genetic link to the disease. To further study this possibility, the frequencies of HLA-A, B, C, and DR antigens were determined in a group of 47 black patients with HAN. Included in the analyses is a subgroup of 16 patients with biopsy-proven focal glomerulosclerosis. Patient frequencies were compared with three separate control populations, the first a normal black population from New York City, the second from a national registry, and the third a group of blacks with idiopathic focal glomerulosclerosis. Only the frequency of HLA-BW53 was consistently increased significantly in the patients as compared with the control groups. This finding supports the notion that a genetic predisposition may exist in the addicted population for the development of renal disease.

Possible genetic predisposition to idiopathic focal segmental glomerulosclerosis.

HLA-A, B, and DR antigen frequencies were studied in a group of 57 patients to determine possible inborn susceptibility to idiopathic focal segmental glomerulosclerosis (FSGS). There were 34 white patients and 23 black patients, most of whom had nephrotic syndrome and later developed renal failure. HLA-DR4 was significantly increased in both patient groups when compared with their respective control groups. This association has not been previously reported. Of note, the association with DR4 was most striking in patients with adult onset disease (in blacks, relative risk equals 5.2; in whites, relative risk equals 5.8). No other antigen was increased in both patient groups but HLA-A28 was increased in blacks. These data support the notion of genetic predisposition to focal segmental glomerulosclerosis in two different ethnic groups.

Percutaneous transluminal angioplasty of splanchnic arteries: an alternative method to elective revascularisation in chronic visceral ischaemia.

Percutaneous transluminal angioplasty of stenoses of superior mesenteric arteries was performed in 4 patients with abdominal angina. Repeat angioplasty had to be performed in 2 patients after restenosis revealed by angiography. Symptomatic relief was obtained in all patients. The patients were followed up for 8-42 months without acute mesenteric ischaemia syndrome. No surgical intervention was required.

CT appearance of giant colonic diverticulum.

The plain film, barium enema, and CT findings in a case of giant colonic diverticulum with the atypical feature of marginal calcifications are presented. The value of CT in the diagnosis and evaluation of giant colonic diverticulum is discussed.

Tuberculous arthritis in a hemodialysis patient.

Tuberculosis (TB) is a relatively common infectious complication in the dialysis population. Most cases are extrapulmonary and pose a diagnostic dilemma for the clinician. Tuberculous arthritis is a rare form of extrapulmonary TB occurring in approximately 1% of cases in nonuremics. Only 1 case in a dialysis patient (not proven by positive synovial fluid culture) has been reported. We report here a culture-proven case of tuberculous arthritis in a hemodialysis patient which masqueraded as an acute septic arthritis. TB should be considered early as an etiologic agent along with synovial biopsy when the exact cause of a monoarthritis has not been discovered, thus avoiding delay in initiation of appropriate therapy.