Tumour markers in internal medicine: a low-cost test or an unnecessary expense? A retrospective study based on appropriateness.

OBJECTIVE AND BACKGROUND: In the last 35 years tumour markers (TM) have gained currency in clinical practice. However, in the light of indications by international guidelines, their use is often unjustified. Our aim was to quantify the use of some of the most common TM, assessing their appropriateness and their efficacy in an Internal Medicine Unit. METHODS: In the three Internal Medicine Units of the Department of Internal Medicine of Policlinico of Modena we have carried out a retrospective analysis of the assessment of the main TM (CEA, CA19.9, CA 125, CA 15.3, NSE). The analysis was divided into two distinct phases: (I) quantitative phase, in order to assess the scale of the problem in economical terms; (II) qualitative phase, in order to assess the efficacy of the tests and the appropriateness of their use. RESULTS: (I) At last one of the considered TM was requested in 5102 out of the 8253 admitted patients (62%) (period 2001-2003). The trend was similar in all three units examined. (II) The qualitative analyses revealed: (1) the most common motivation for their use (79%) was diagnostic, mostly prior to any other test; (2) a mere 5% of the requests were appropriate according to the international literature; and (3) TM showed a low positive predictive value when used for diagnosis in an unselected population such as that of an Internal Medicine unit. CONCLUSIONS: The results of our study showed that TM determination represents an overall cost for Internal Medicine units and that there is a high inappropriateness in their use compared to what it is suggested by international guidelines. Though the TM is a low-cost test when used correctly, it seems an unnecessary expense if not adequately incorporated into the decision making process.

[Primary hyperparathyroidism]. / Iperparatiroidismo primitivo.

Primary hyperparathyroidism (PHPT) is characterized by excessive PTH secretion in respect to calcium homeostasis needs, due to parathyroid adenoma (80% of cases), hyperplasia (15-20%), or carcinoma (1-2%). In familial forms of PHPT, several mutations have an established role: menin gene for MEN type 1, RET for MEN type 2a, calcium-sensing receptor gene for familial hypocalciuric hypercalcemia, parafibromin gene for PHPT-jaw tumour and carcinoma. Etiology of sporadic adenomas (80% of PHPT cases) is less defined, being most commonly found a mutation of menin gene or activation of PRAD1 oncogene. In recent years, the classical features of the disease became less common. Typically, bone involvement is now represented by a reduced bone mass at skeletal sites more rich in cortical tissue. Prominently trabecular skeletal sites are relatively spared, because of the anabolic effects of a slight PTH excess on trabecular tissue. PHPT patients may have increased fracture risk, though it is not clear why bone damage is more severe in a subgroup of patients. Clinical features of hypercalcemia may be fatigue, anorexia, thirst, and polyuria. Vague neurological and psychiatric symptoms, such as weakness, anxiety, depression, paresthesias, and muscular cramps may ameliorate after parathyroidectomy. Recent reports indicate increased cardiovascular mortality in PHPT patients. Diagnosis is based on the detection of hypercalcemia, together with inappropriately high serum PTH levels. Preoperative localization of the diseased glands is mandatory in persistent or recurrent PHPT, as like as when minimally invasive surgery is planned. High resolution ultrasonography and SPECT double-phase 99m Tc-sestamibi scintigraphy are the most commonly employed techniques. Intraoperatory PTH assay may confirm successful surgery when serum concentrations decrease more than 50%. Surgical therapy is indicated in patients with renal or skeletal complications, such as in those with previous parathyrotoxic crisis. Many surgeons in recent years adopted minimally invasive parathyroidectomy. Medical treatment is an option for patients unwilling or unfitted for surgery because of severe concomitant diseases. Employed therapy includes estrogens, SERMs, bisphosphonates and calcimimetics.

Prevalence of hypercalcemia in hospitalised patients: effects of "correction" for serum albumin values.

Hypercalcemia is ideally detected by the measurement of serum ionised calcium. Because this is not widely available, in common clinical practice "albumin-corrected" calcium values are often utilized. Our study investigated whether the method used to measure serum albumin concentration may significantly interfere in the derived serum calcium values and, consequently, in the identification of hypercalcemic patients. In 170 consecutive patients admitted to our Department of Internal Medicine we measured serum total calcium, total protein, and albumin by colorimetric method; albumin concentration was also derived by electrophoresis assessment. After correcting serum calcium for colorimetrically (CA) and electrophoretically (EA) measured albumin values, the detected frequencies of hypercalcemia were compared, utilizing different cut-off limits (i.e. 11.0, 10.4 and 10.2 mg/dl). In our patients, the CA values were significantly lower than EA levels. As a consequence, EA-corrected calcium, as well as total calcium concentration were significantly lower than CA-corrected values. This may also account for the very different prevalence of hypercalcemic patients identified by serum total, EA-corrected and CA-corrected calcium values. Our data therefore indicate the importance of the method of albumin measurement in the determination of "corrected" calcium concentration.

Numerical simulation of a child restraint system in an aircraft crash-test.

Studies conducted at the FAA Civil Aeromedical Institute have shown that when used in aircraft, automotive child restraint devices do not always provide the level of safety desired. Various factors that contribute to poor performance, such as seat belt anchor location, cushion stiffness, and child restraint device design features, were evaluated by a dynamic impact test program. To efficiently continue the research, a computer model was developed using MADYMO. Results of two of the impact tests were used to validate the model. Both test configurations utilized a typical commercial transport airplane passenger seat and a popular automotive child restraint device. These tests were considered representative of the extremes of child restraint device and occupant kinematics due to variance in seat belt anchor location. Details are presented of the test parameters and geometry, as well as cushion and restraint system properties. Test and modelling results for these two impact conditions are summarized and compared. Parametric studies were then conducted that used the model to investigate the effect of cushion stiffness, belt anchor spacing, and initial belt tension.