Adverse outcome analyses of observational data: assessing cardiovascular risk in HIV disease.

Clinical decisions are ideally based on randomized trials but must often rely on observational data analyses, which are less straightforward and more influenced by methodology. The authors, from a series of expert roundtables convened by the Forum for Collaborative HIV Research on the use of observational studies to assess cardiovascular disease risk in human immunodeficiency virus infection, recommend that clinicians who review or interpret epidemiological publications consider 7 key statistical issues: (1) clear explanation of confounding and adjustment; (2) handling and impact of missing data; (3) consistency and clinical relevance of outcome measurements and covariate risk factors; (4) multivariate modeling techniques including time-dependent variables; (5) how multiple testing is addressed; (6) distinction between statistical and clinical significance; and (7) need for confirmation from independent databases. Recommendations to permit better understanding of potential methodological limitations include both responsible public access to de-identified source data, where permitted, and exploration of novel statistical methods.

Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than iron dextrans.

Use of recombinant human erythropoietin in patients with end-stage renal disease has highlighted iron deficiency as the major cause of resistant anemia. The current mainstay of intravenous (i.v.) iron replacement therapy, iron dextran, has been shown in prior studies to have a risk of serious life-threatening anaphylaxis of just under 1 per 100 patients exposed. The current study assessed the safety profile of an alternative i.v. iron, sodium ferric gluconate complex in sucrose (Ferrlecit), as compared with iron dextrans. Sodium ferric gluconate complex in sucrose, a unique chemical preparation, has been in use since 1959, principally in Europe, at a rate of approximately 2.7 million i.v. doses per year (1992 to 1996) in Germany and Italy alone. For iron dextran, usage in the United States was comparable--principally renal hemodialysis--and estimated from market sources at 3.0 million doses per year (1995). From 1976 to 1996, there were 74 allergic adverse events reported for sodium ferric gluconate complex in sucrose to the World Health Organization (WHO), German Health Bureau, and the manufacturer (all combined). For the years 1992 to 1996, sodium ferric gluconate complex in sucrose had an allergy event reporting rate of 3.3 allergy episodes per million doses per year compared with a similar rate of 8.7 reported allergy events per million doses per year for iron dextran in the United States in 1995. Case fatalities for sodium ferric gluconate complex in sucrose and iron dextran within these reports were then compared. For sodium ferric gluconate complex in sucrose, there were no reports of deaths over the entire period (1976 to 1996). However, for iron dextrans, there were 31 fatalities among 196 allergy/anaphylaxis cases reported in the United States between 1976 and 1996, yielding a case-fatality rate of 15.8%. These data show that sodium ferric gluconate complex in sucrose, when compared with iron dextrans in comparably sized patient usage populations with similar total rates of reporting of allergic events, has a significantly lower reported mortality rate (P < 0.001). Thus, the data justify usage of sodium ferric gluconate complex in sucrose as the safer iron replacement therapeutic agent.

Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial.

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.

Iron deficiency in patients with renal failure.

The anemia of renal failure is caused by the lack of sufficient quantities of endogenous erythropoietin. With the availability of recombinant human erythropoietin (rHuEPO), however, it has become apparent that to achieve a given target, hematocrit requires proper management of iron replacement, as well as the administration of rHuEPO. Iron deficiency, either absolute or functional, will occur in most, if not all, patients on hemodialysis receiving rHuEPO because of the increased demand for iron driven by the accelerated erythropoiesis that occurs with exogenous rHuEPO administration, coupled with ongoing blood losses from dialyzer and tubing, blood sampling, gastrointestinal blood loss, and blood losses at the time of dialysis needle placement and removal. Blood loss is less of a problem in patients on peritoneal dialysis, but poor iron intake and increased demand for iron are also seen, the latter in patients receiving rHuEPO. It is essential, therefore, for renal health professionals to understand iron metabolism in dialysis patients in order to properly balance the therapy of renal anemia with rHuEPO and supplemental iron.

Tightening the screw: statutory and legal supervision of interhospital patient transfers.

A federal statute governing the transfer of indigent patients from Medicare-enrolled hospitals was first enacted in 1986. Review of the statutory and other legal controls over interhospital transfers is precipitated by its recent amendment and the fining of a Texas physician for transferring a high-risk obstetric patient without following the statutory guidelines. These events are part of a pattern of increasing regulation of the practice of medicine. Physicians and hospital administrators responsible for hospital transfer policies should be aware of regulatory developments. Hospitals contemplating transfer of patients must develop transfer policies that comply with governing law, including state law. A transfer policy should provide guidelines as to when a patient is "stable for transfer". Patients may not be transferred unless a physician can certify that delay attendant to transfer will not be detrimental. Furthermore, the policy should specify the procedures to be followed to effect a transfer and any documentation that the physician will have to complete.