We report two cases in which osteomalacia developed in patients on tenofovir-containing highly active antiretroviral therapy (HAART) in the context of Fanconi syndrome with hypophosphataemia. Bone pain was the presenting feature and myopathy followed in one case. Disability was reversed with withdrawal of the drug and with mineral supplementation. The cases highlight the importance of considering the diagnosis of osteomalacia in patients treated with tenofovir. A possible association with incipient acute renal failure, particularly during nonsteroidal anti-inflammatory drug (NSAID) use, needs further investigation.Keywords: HIV infections, hypophosphataemia, myopathy, osteomalacia, tenofovir Received: 28 September 2004, accepted 18 February 2005 Introduction Reduced bone mineral density has become increasingly important within the HIV-infected cohort as longevity has increased. It has been documented in a number of studies [1,2] and is possibly linked to the use of highly active antiretroviral therapy (HAART) [3], although, in studying this effect, it is difficult to separate the relative contributions made by length of time since diagnosis and HAART use, the two being interdependent.Osteomalacia, however, has been documented in only a few cases [4] and the myopathy of osteomalacia not at all. Tenofovir causes recognized Fanconi syndrome and hypophosphataemia [5,6], although osteomalacia has rarely been linked to such treatment [7]. Osteomalacia has also occasionally been linked to cidofovir and adefovir, other nucleotide analogues [7]. In animal studies using high-dose tenofovir, osteomalacia was a frequent adverse event [8]. In other settings, however, Fanconi syndrome is known to cause osteomalacia and myopathy, which is reversible if the underlying cause can be corrected [9]. Such instances have included Fanconi syndrome secondary to monoclonal gammopathy [10] and ifosfamide treatment [11]. Hypophosphataemia caused by malabsorption syndrome [12], parathyroid hormone-related protein-producing tumours or other tumours (so called oncogenic osteomalacia) [13][14][15] also produces a reversible osteomalacia, mediated via the phosphaturic hormones fibroblastic growth factor 23 (FGF 23) and matrix extracellular phosphoglycoprotein (MEPE), themselves controlled by the membrane metalloprotease PHEX [16]. In such cases the hypophosphataemia can lead to pathological fractures and tetany [15]. Fractures or Looser's zones can be misdiagnosed as disseminated malignancy, leading to diagnostic delay and disability [17]. Case 1A 47-year-old homosexual man was diagnosed with AIDS in 1989. His past medical history had included Kaposi sarcoma (treated in 1999) and hepatitis B infection (now surface antigen negative), but no abnormality of blood pressure, of renal function, or of phosphate metabolism and no history of a concomitant potentially nephrotoxic agent. He had been on antiretroviral therapy since 1991, with a triple class resistant virus.In February 2002, as a result of virological failure on his previous salvage regime...

There has been concern about the performance of CURB-65 in older patients with community-acquired pneumonia (CAP) and that younger patients who subsequently die are initially misclassified as having non-severe CAP. The purpose of this study was to evaluate the effect of age on the performance of CURB-65. We analysed data prospectively, collected in two UK hospitals. Patients were stratified into four age cohorts. Mortality in each cohort was then stratified by CURB-65 score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating curve (AUROC) were calculated. Four hundred and twenty-eight patients were included. Misclassification of patients who subsequently died as non-severe CAP patients (CURB-65 score of < or =2) increased with increasing age (from 3% in the <65-year cohort to 27% in those aged >85 years). There were no deaths (0/105) in those aged <65 years who had a CURB-65 score of 0 or 1. At the British Thoracic Society cut-off for severe CAP (CURB-65 score of > or =3), CURB-65 performed best in 16-64-year-olds (PPV 0.4, NPV 0.97). The AUROC was significantly higher for the <65-year cohort in comparison with older patients (0.93 vs. 0.7, p <0.05). Clinicians should interpret the CURB-65 score with care in older patients referred to hospital with CAP. In those aged <65 years, however, CURB-65 appears to be able to identify a cohort of patients (CURB-65 score of 0 or 1) with very low mortality.

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Background: Intravenous amphotericin or intravenous voriconazole, both followed by oral voriconazole, have previously been given to treat invasive aspergillosis of the skull base.Case report: Exclusively oral voriconazole was used in an immunocompetent patient with biopsy-proven, invasive aspergillosis. She had a large, erosive lesion extending from the central skull base to the right orbit and ethmoid sinus, and displacing the right internal carotid artery. After four months of oral treatment as an out-patient, a repeated computed tomography scan showed a fully treated infection with post-infectious changes only, and treatment was terminated. Two years later, there had been no recurrence.Conclusion: Substantial cost savings were made by using exclusively oral treatment, compared with the use of intravenous voriconazole or amphotericin, or a switch strategy.

We believe that this model of care may be suitable for the management of patients with bacteraemia. A study assessing the cost-effectiveness of this approach is required.