An analysis for menstrual data with time-varying covariates

This paper concerns the analysis of menstrual data; in particular, methodology to identify variables that contribute to the variability of menstrual cycles both within and between women. The basis for the proposed methodology is a parameterization of the mean length of a menstrual cycle conditional upon the past cycles and covariates. This approach accommodates the length-bias and censoring commonly found in menstrual data. Data from a longitudinal study of menstrual patterns and other variables among Lese women of the Ituri Forest, Zaire, illustrate the methodology. A small simulation illustrates the bias caused by incorrectly deleting the censored cycles.     

Continuous warm blood cardioplegia preserves cardiac autonomic function.

We studied in anesthetized dogs, the effects of cardiopulmonary bypass with normothermic whole blood, crossclamping of the aortic root, and continuous warm blood cardioplegia on the ability of the efferent sympathetic nervous system to augment the heart and that of the efferent parasympathetic nervous system to depress the heart. In control states, heart rate, atrial force of contraction, and right and left ventricular wall systolic pressures were augmented by stimulation of the intrathoracic efferent sympathetic nervous system and by administration of isoproterenol into the systemic circulation. After 1 hour of normothermic cardiopulmonary bypass that utilized aortic crossclamping and continuous perfusion of the coronary arteries with normothermic blood (20 mEq/L potassium), cardiac-augmenting effects induced by the efferent sympathetic nervous system and by isoproterenol were similar. Depressive responses elicited by the efferent parasympathetic nervous system were also unaffected by these procedures. Continuous warm blood cardioplegia does not result in impairment of the efferent sympathetic nervous system regulating the heart.     

A high performance liquid chromatography method for the detection of brodifacoum in serum

A procedure for the detection of brodifacoum (BDF) in serum was developed. Extraction of BDF was achieved by acidification of 2 ml of serum with 1 ml of 1.5% acetic acid followed by dual extractions with 10 ml diethyl ether and ether: acetonitrile [1:1]. In spiking experiments, 68 +/- 3, 61 +/- 4 and 65 +/- 5% of added BDF was recovered from serum containing 1000, 100 and 25 ng BDF/ml, respectively. Two high performance liquid chromatography solvent systems were used for chromatographic separation (A: 1.5% acetic acid, pH 4.5: acetonitrile [1:2] with 1% dibutylamine; and B:O.2 M tris(hydroxymethyl)aminomethane, pH 7.5:acetonitrile [1:3]). Detection limits were 75 and 3 ng BDF/ml of serum using ultraviolet absorption (254 nm) and fluorescence measurement (313 nm excitation, 375 nm emission), respectively. This method has been used successfully to monitor serum concentrations of BDF in experimental and field cases of exposure.     

Differential effects of substance P on serotonin-modulated spinal nociceptive reflexes

Recent immunohistochemical studies indicate the presence of a bulbospinal substance P (SP) system, as well as a bulbospinal serotonin (5-HT) system, involved in spinal pain transmission. Although electrophysiological studies indicate that SP may modulate the effects of 5-HT on post-synaptic spinal nociceptive neurons, the functional relationship between SP and 5-HT on “pain behavior” remains obscure. To bridge this gap between mechanism and behavior, the purpose of the present study was to determine specific postsynaptic behavioral effects of SP and 5-HT on local spinal nociceptive reflexes in spinally transected animals. Administration of the 5-HT agonists 5-methoxydi-methyltryptamine (5-MeODMT) (0, 0.5, 1.5, 2.0 mg/kg) and quipazine (0, 5, 10, 20 mg/kg) 2 days after transection significantly expanded the receptive field (RF) areas of three spinal reflexes, as previously reported. Intrathecal administration of SP alone (0, 0.25, 2.5, 7.5 ng) also resulted in hyperalgesia, indicated by a significant expansion of the RF areas of all three nociceptive reflexes. However, administration of SP, in animals pretreated with 5-HT agonists, decreased the 5-HT-induced expansion of RF size. Therefore, SP had opposite effects on spinal nociceptive reflexes depending on whether or not the animal was pretreated with 5-HT agonists, i.e., hyperalgesia in the absence of 5-HT agonists, and analgesia in the presence of 5-HT agonists. The two effects of SP on local spinal reflexes may be related to the anatomical organization of the two spinal SP systems: 1) SP released from primary afferents facilitates nociceptive reflexes, and 2) SP associated with the descending bulbospinal system interacts with the descending bulbospinal 5-HT system and inhibits nociceptive reflexes. The present results help explain contradictory literature regarding the effect of SP on spinal nociceptive reflexes.     

Further evidence supporting a cause and effect relationship between blood transfusion and earlier cancer recurrence.

Studies of associations between perioperative blood transfusions and later recurrence of solid tumors have yielded conflicting results. A previous analysis of transfused patients suggested that recurrence was associated with transfusion of whole blood as opposed to red blood cell concentrates. Additional analyses were performed on patients with cancers of the colon, rectum, cervix, and prostate to determine if patients receiving whole blood, red blood cells only, or no transfusions had differing outcomes. Patients receiving 1 unit or more of whole blood had uniformly poor outcomes compared with nontransfused patients (p less than 0.001). In contrast, patients receiving only red blood cells had progressively worse recurrence and death rates with increasing numbers of transfusion, suggesting the presence of a dose-effect relationship. Employing multivariate techniques, blood transfusion of less than or equal to 3 units that included any whole blood were independently and significantly associated with earlier recurrence (p = 0.003) and death due to cancer (p = 0.02). Transfusions of less than or equal to 3 units of blood comprised solely of red blood cell concentrates were associated with no greater risk of recurrence than that seen in patients receiving no transfusion (p = 0.50). These results provide a potential explanation for the disparate results reported in studies of blood transfusion and cancer outcome. The marked difference in outcome seen between patients receiving a few units of red blood cells and comparable patients receiving even one unit of whole blood are consistent with the hypothesis that transfusion of stored blood plasma causes earlier tumor recurrence in some instances. Strategies for reducing these risks might include avoidance of whole blood transfusions when only 1-3 units are required, more conservative transfusion practice, use of autologous blood transfusions, and perhaps, use of red blood cells washed free of plasma and white cell debris. Clinical trials to test these hypotheses are urgently needed.     

Life-sustaining therapy. A model for appropriate use

New strategies are needed to curb the proliferation of life-sustaining therapies that rarely benefit patients. We propose a model for appropriate use of such therapies that incorporates effectiveness, utility, and marginal costs. If a therapy is rarely effective and rarely desirable, it is considered medically inappropriate. If the marginal cost-effectiveness ratio is inordinately high, it is considered economically inappropriate. If a therapy is either medically or economically inappropriate, it should not be automatically offered. The model provides an operational definition of futility and is illustrated with an analysis of out-of-hospital cardiopulmonary resuscitation for chronically ill older people. Advance directives, explicit health care rationing, and defining futile therapy based on survival predictions are alternatives to the appropriate care model, but are insufficient strategies to solve the problem of inappropriate life-sustaining care.