Economic evaluation of four follow-up strategies after curative treatment for breast cancer: results of an RCT.

BACKGROUND: An economic evaluation was performed alongside a randomised controlled trial (ISRCTN 74071417) investigating the cost-effectiveness of nurse-led telephone follow-up instead of hospital visits, and of a short educational group programme (EGP) in the first year after breast cancer treatment. METHOD: This economic evaluation (n = 299) compared the one-year costs and the effects of four follow-up strategies: (1) hospital follow-up; (2) nurse-led telephone follow-up; (3) hospital follow-up plus EGP; and (4) nurse-led telephone follow-up plus EGP. Costs were measured using cost diaries and hospital registrations. Quality-adjusted life years (QALYs) were measured using the EQ-5D. Outcomes were expressed in incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves. RESULTS: Hospital follow-up plus EGP yielded most QALYs (0.776), but also incurred the highest mean annual costs (€4914). The ICER of this strategy versus the next best alternative, nurse-led telephone follow-up plus EGP (0.772 QALYs and €3971), amounted to €235.750/QALY. Hospital and telephone follow-up without EGP both incurred higher costs and less QALYs than telephone follow-up plus EGP and were judged inferior. Hospital follow-up plus EGP was not considered cost-effective, therefore, telephone follow-up plus EGP was the preferred strategy. The probability of telephone follow-up plus EGP being cost-effective ranged from 49% to 62% for different QALY threshold values. Secondary and sensitivity analyses showed that results were robust. CONCLUSION: Nurse-led telephone follow-up plus EGP seems an appropriate and cost-effective alternative to hospital follow-up for breast cancer patients during their first year after treatment.

Nurse-led telephone follow-up and an educational group programme after breast cancer treatment: results of a 2 × 2 randomised controlled trial.

OBJECTIVE: To investigate whether frequent hospital follow-up in the first year after breast cancer treatment might partly be replaced by nurse-led telephone follow-up without deteriorating health-related quality of life (HRQoL), and whether a short educational group programme (EGP) would enhance HRQoL. PATIENTS AND METHODS: A multicentre pragmatic randomised controlled trial (RCT) with a 2×2 factorial design was performed among 320 breast cancer patients who were treated with curative intent. Participants were randomised to follow-up care as usual (3-monthly outpatient clinic visits), nurse-led telephone follow-up, or the former strategies combined with an educational group programme. The primary outcome for both interventions was HRQoL, measured by EORTC QLQ-C30. Secondary outcomes were role and emotional functioning and feelings of control and anxiety. RESULTS: Data of 299 patients were available for evaluation. There was no significant difference in HRQoL between nurse-led telephone and hospital follow-up at 12 months after treatment (p = 0.42; 95% confidence interval (CI) for difference: -1.93-4.64) and neither between follow-up with or without EGP (p = 0.86; 95% CI for difference: -3.59-3.00). Furthermore, no differences between the intervention groups and their corresponding control groups were found in role and emotional functioning, and feelings of control and anxiety (all p-values > 0.05). CONCLUSION: Replacement of most hospital follow-up visits in the first year after breast cancer treatment by nurse-led telephone follow-up does not impede patient outcomes. Hence, nurse-led telephone follow-up seems an appropriate way to reduce clinic visits and represents an accepted alternative strategy. An EGP does not unequivocally affect positive HRQoL outcomes.

Ectopic gastric mucosa in the lower esophagus, presenting as a sessile polyp.

A patient with dysphagia caused by a sessile polyp in the lower esophagus is reported. Histologic examination showed ectopic gastric mucosa. Of the benign tumors of the esophagus, only leiomyoma is seen regularly. The remaining tumors are so rare that the consequences of this diagnosis are unclear. When symptoms make treatment necessary, local excision is preferred.

Posttraumatic complications and inflammatory mediators.

In a series of 71 patients with trauma, we measured weekly the blood levels of a number of complement proteins and activation products. We also measured the following: leukocytes, platelets, granulocyte enzyme elastase, alpha 1-antitrypsin, total protein, albumin, haptoglobin, and fibronectin. The intensity of complement activation and the blood levels of elastase correlated with the following factors: injury severity (especially the severity of limb injury), development of adult respiratory distress syndrome, development and severity of multiple organ failure, and probability of a fatal outcome. The plasma elastase level seemed to be the best predictor of adult respiratory distress syndrome and the best correlate of injury severity and multiple organ failure severity. Our findings support the hypothesis that posttraumatic activation of the complement system leads to activation of granulocytes, followed by microvascular injury and finally by organ failure.

Multiple-organ failure and sepsis without bacteria. An experimental model.

Multiple-organ failure is generally attributed to bacterial infection, although a correlation with positive blood cultures is not consistently found. Consequently, we studied the effects of a local nonbacterial inflammatory stimulus on distant organ functions and metabolism. Wistar rats were inoculated intraperitoneally with zymosan. Heart and ventilatory rates, oxygen consumption, and body temperature were measured. Survivors were killed at day 12 for blood analysis, weighing of organs, and microscopy. Intraperitoneal zymosan resulted in an early hyperdynamic "septic" response with a 35% mortality. After a few days, oxygen consumption decreased, serum lactate levels increased, and the function of multiple organs deteriorated, while blood cultures remained sterile. The experiment was repeated in germ-free rats with similar results but a lower mortality. We concluded that a severe inflammatory response in itself is capable of inducing multiple-organ failure with "sepsis."

Acute generalized microvascular injury by activated complement and hypoxia: the basis of the adult respiratory distress syndrome and multiple organ failure?

It has been suggested that generalized endothelial damage and permeability changes, induced by prolonged activation of the complement system and ensuing release of lysosomal enzymes, prostaglandins and toxic oxygen products, underlie the genesis of the Adult Respiratory Distress Syndrome (ARDS) and Multiple Organ Failure (MOF). The effects in New Zealand white rabbits were investigated of a 4 h infusion of activated complement and its combination with a short hypoxic episode on respiratory function, leukocyte count, platelet count and morphology of the lungs, heart, liver, kidney and spleen. Prolonged activation of the complement system induced hyperventilation with respiratory alkalosis and hypocapnia, depletion of granulocytes (PMN), and a variable accumulation PMN in the capillaries of all organs examined, in combination with interstitial, and, in the liver, cellular oedema. Electron microscopy of the lungs revealed degranulation of PMN, endothelial swelling and widening of the alveolar septa. The combination of hypoxia and systemic complement activation appeared to aggravate this microvascular injury with the occurrence of protein rich alveolar oedema and haemorrhage in the lungs and accumulation of PMN debris containing macrophages in the spleen. The alterations in respiratory function and pulmonary morphology in these rabbits, imitate the clinical and morphological characteristics of the early phase of ARDS. The inflammatory reaction, found in all other organs examined, might represent the early phase of MOF. If so, ARDS and MOF -- clinically closely interconnected syndromes -- might be interpreted as manifestations of the same syndrome and as the clinical expression of an uncontrolled whole body inflammation.

Pathophysiology of the adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF)--a hypothesis.

A review of the recent literature concerning the Adult Respiratory Distress Syndrome (ARDS) and Multiple Organ Failure (MOF) is presented. We hypothesize that the two syndromes probably have a common pathophysiology, with ARDS as the first occurring organ failure. The clinical situations that may cause ARDS and MOF are characterized by massive and prolonged activation of the complement system. This results in activation of granulocytes with ensuing release of lysosomal enzymes, toxic oxygen products and prostaglandins, which collectively cause endothelial damage and permeability changes. In the lungs interstitial and alveolar edema develops, with an impaired alveolo-capillary gas exchange. Oxygen diffusion in the peripheral tissues is impeded by the same mechanism, ultimately resulting in organ failure. Hypoxia may cause additional microvascular lesions, as toxic oxygen radicals are produced during reoxygenation. The implications of this hypothesis for the prevention and therapy of ARDS and MOF are discussed.

Multiple-organ failure. Generalized autodestructive inflammation?

As multiple-organ failure (MOF) has been generally associated with sepsis, the importance of bacterial sepsis was evaluated retrospectively in 55 trauma and 37 intra-abdominal-sepsis patients with MOF. The severity of MOF was graded, and an analysis was made of day of onset, incidence, severity, sequence, and mortality of organ failures. No difference was found between groups in sequence, severity, or mortality of organ failures. In contrast, bacterial sepsis was found in 65% of intra-abdominal-sepsis patients but only in 33% of trauma patients. It is concluded that sepsis is probably not the essential cause of MOF. Instead, an alternative hypothesis is presented involving massive activation of inflammatory mediators by severe tissue trauma or intra-abdominal sepsis, resulting in systemic damage to vascular endothelia, permeability edema, and impaired oxygen availability to the mitochondria despite adequate arterial oxygen transport.