Interventions to support shared decision-making for women with heavy menstrual bleeding: A systematic review.

This review studies women's preferences for shared decision-making about heavy menstrual bleeding treatment and evaluates interventions that support shared decision-making and their effectiveness. PubMed, Cochrane, Embase, Medline and ClinicalTrials.gov were searched. Three research questions were predefined: 1) What is the range of perspectives gathered in studies that examine women facing a decision related to heavy menstrual bleeding management?; 2) What types of interventions have been developed to support shared decision-making for women experiencing heavy menstrual bleeding?; and 3) In what way might women benefit from interventions that support shared decision-making? All original studies were included if the study population consisted of women experiencing heavy menstrual bleeding. We used the TIDieR (Template for Intervention: Description and Replication) checklist to assess the quality of description and the reproducibility of interventions. Interventions were categorized using Grande et al. guidelines and collated and summarized outcomes measures into three categories: 1) patient-reported outcomes; 2) observer-reported outcomes; and 3) doctor-reported outcomes. Fifteen studies were included. Overall, patients preferred to decide together with their doctor (74%). Women's previsit preference was the strongest predictor for treatment choice in two studies. Information packages did not have a statistically significant effect on treatment choice or satisfaction. However, adding a structured interview or decision aid to increase patient involvement did show a positive effect on treatment choice and results, patient satisfaction and shared decision-making related outcomes. In conclusion shared decision-making is becoming more important in the care of women with heavy menstrual bleeding. Structured interviews or well-designed (computerized) tools such as decision aids seem to facilitate this process, but there is room for improvement. A shared treatment choice is only possible after careful provision of information, elicitation of patients' preferences and integrating those preferences. Interventions should be designed accordingly.

Determination and quantification of sulfadiazine and trimethoprim in swine tissues using liquid chromatography with ultraviolet and mass spectrometric detection.

High-performance liquid chromatographic procedures with ultraviolet detection were developed for the quantitative determination of sulfadiazine (SDA) and trimethoprim (TMP) in swine tissues (kidney, liver, muscle, fat and fat + skin). In addition, high-performance liquid chromatography with atmospheric pressure chemical ionization mass spectrometry was used for the confirmation of the identity of the analytes of interest. Chromatographic separation was achieved on a Spherisorb ODS-2 column (250 x 4.6 mm id, dp 5 microns). The mobile phase for SDA analysis consisted of 1% acetic acid in water-acetonitrile (85 + 15, v/v). For TMP analysis a 80 + 15 + 5 (v/v/v) mixture of 0.25% triethylammonium acetate in water, acetonitrile and methanol was used as the eluent. Sulfamerazine and ormethoprim were used as the internal standards for SDA and TMP analysis, respectively. For the isolation of the compounds of interest from biological samples, a liquid-liquid extraction with acetone and ethyl acetate, followed by a clean-up using a solid-phase extraction column (aminopropyl and benzenesulfonic acid for SDA, benzenesulfonic acid for TMP) was performed. Calibration graphs were prepared for all tissues and linearity was achieved over the concentration ranges tested (50-1000 ng g-1 for SDA, r > or = 0.9979; 25-500 ng g-1 for TMP, r > or = 0.9994). The method was validated at the maximum residue level (MRL, 100 ng g-1 for SDA and 50 ng g-1 for TMP), at half the MRL and at double the MRL for both SDA and TMP. The accuracy and precision (expressed as the within-day repeatability) were found to be within the required ranges for each specific concentration. The quantification limits were 50 ng g-1 for SDA and 25 ng g-1 for TMP. The limits of detection were below one half the MRLs. Both methods were selective for the determination of SDA and TMP. Biological samples (kidney, liver, muscle, fat and fat + skin) from pigs that received a commercial SDA-TMP preparation with the feed for five consecutive days (dose rate: 25 mg SDA and 5 mg TMP kg body weight-1 day-1) were analyzed using the described methods. The quantitative results were used to calculate a withdrawal time (12 days) to reach residue levels below the respective MRLs. This calculation was performed according to the recommendations of the European Agency for the Evaluation of Medicinal Products (EMEA/CVMP/036/95).

Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain.

Alzheimer's disease (AD) is a major dementing illness characterized by regional concentrations of senile plaques, neurofibrillary tangles, and extensive neuronal cell death. Although cell and synaptic loss is most directly linked to the severity of symptoms, the mechanisms leading to the neuronal death remain unclear. Based on evidence linking neuronal death during development to unexpected reappearance of cell cycle events, we investigated the brains of 12 neuropathologically verified cases of Alzheimer's disease and eight age-matched, disease-free controls for the presence of cell cycle proteins. Aberrant expression of cyclin D, cdk4, proliferating cell nuclear antigen, and cyclin B1 were identified in the hippocampus, subiculum, locus coeruleus, and dorsal raphe nuclei, but not inferotemporal cortex or cerebellum of AD cases. With only one exception, control subjects showed no significant expression of cell cycle markers in any of the six regions. We propose that disregulation of various components of the cell cycle is a significant contributor to regionally specific neuronal death in AD.

Residue study of doxycycline and 4-epidoxycycline in pigs medicated via-drinking water.

A study was performed to determine the residues in edible tissues of healthy pigs after continuous administration of doxycycline with drinking water for five consecutive days at a dose rate of 10.5 mg doxycycline kg-1 body weight (BW) per day. Quantitation was performed using a validated HPLC method with fluorescence detection. The method was able to separate doxycycline and its 4-epimer, 4-epidoxycycline. This epimer was found in kidney, liver, skin, fat and muscle tissue. The method was validated at the maximum residue limit (MRL), at half the MRL and at double the MRL for both doxycycline and 4-epidoxycycline. Linear calibration curves were obtained in spiked tissues (r > 0.99). The accuracy of the calibrators of the calibration curves was within -20% to +10%. The accuracy and precision (expressed as the within-run repeatability) were found to be within the required ranges for the specific concentration. The limits of detection and limits of quantification were below one-half of the MRL. The quantification limits were 50 micrograms kg-1 for doxycycline and 100 micrograms kg-1 for 4-epidoxycycline in kidney and liver, 20 micrograms kg-1 for doxycycline and 50 micrograms kg-1 for 4-epidoxycycline in skin and fat and 10 micrograms kg-1 for doxycycline and 50 micrograms kg-1 for 4-epidoxycycline in muscle tissue. The withdrawal time was calculated according to the recommendations of the European Agency for the Evaluation of Medicinal Products (EMEA/CVMP/036/95) and was set at 3 days. The plasma concentration of doxycycline and the stability of doxycycline in drinking water were also determined during the treatment period. The mean plasma concentration of doxycycline during the treatment period ranged from 0.83 to 0.96 microgram ml-1. Thirty-six hours after the withdrawal from medicated drinking water, no plasma levels could be detected. Samples of medicated water were taken at time zero and at 24 h after addition of doxycycline to the drinking water. No statistically significant difference in the mean drinking water concentration was seen at time zero and at time 24 h (Student's t-test, alpha = 0.05).

A rare cause of dyspnea and arterial hypoxemia.

Platypnea-orthodeoxia is a rare pattern of dyspnea with arterial hypoxemia. Platypnea is defined as dyspnea induced by upright posture, and it is relieved by the recumbent position. Orthodeoxia refers to arterial desaturation resulting from assuming an erect or upright position. The case reported involves a 59-year-old man with profound, unexplained dyspnea despite extensive investigation performed at the referring institution. The difficulty in diagnosis persisted until it was recognized that the investigations, in having been performed under "standard" (supine) conditions, were insufficient and therefore misleading. Despite normal supine intracardiac pressures, a patent foramen ovale was shown to give rise to a large orthostatic intracardiac shunt, demonstrated by means of an echocardiogram performed with the patient supine and upright. Surgical closure of the foramen was followed by dramatic clinical improvement. Among dyspneic patients, discernment of a pattern of platypnea and orthodeoxia is key to effective evaluation.

The performance of a limited set of items from the Functional Independence Measure for use in acute trauma care and rehabilitation.

OBJECTIVE: To evaluate the performance of a limited set of three items from the Functional Independence Measure--eating, walking, and expression--(henceforth referred to as the Set) for use in acute trauma care and rehabilitation. DESIGN: Retrospective comparison of the Set-scores (3-item total) to the Functional Independence Measure (FIM) scores in 83 consecutive patients with a primary diagnosis related to trauma (90% of those eligible) over a 2-year period, on an acute rehabilitation unit in a tertiary care university hospital. METHODS: The age distributions of gender and diagnostic categories were examined. The sensitivity and specificity of the Set-score in detecting changes in the FIM were evaluated across a range of cut-off values. Correlation between FIM scores and Set-scores at admission, at discharge, and for interval change were assessed using the intraclass correlation coefficient. Sources of the Set's weaknesses were explored. RESULTS: Age distribution reflects the predisposition of older women to hip fractures and males to the other trauma. No degree of change in the Set-score provided a combination of sensitivity and specificity satisfactory for detecting potentially important changes in the FIM. Intraclass Correlation Coefficients (ICC) for Set-scores and FIM scores on admission and discharge were both .12. The ICC for the interval change data was .11. (95% confidence limits:--.11 to .34). CONCLUSION: This Set is not a useful measure of functional disability in a heterogeneous population of trauma patients.

The induction of multiple cell cycle events precedes target-related neuronal death.

Unexpected nerve cell death has been reported in several experimental situations where neurons have been forced to re-enter the cell cycle after leaving the ventricular zone and entering the G0, non-mitotic stage. To determine whether an association between cell death and unscheduled cell cycling might be found in conjunction with any naturally occurring developmental events, we have examined target-related cell death in two neuronal populations, the granule cells of the cerebellar cortex and the neurons of the inferior olive. Both of these cell populations have a demonstrated developmental dependency on their synaptic target, the cerebellar Purkinje cell. Two mouse neurological mutants, staggerer (sg/sg) and lurcher (+/Lc), are characterized by intrinsic Purkinje cell deficiencies and, in both mutants, substantial numbers of cerebellar granule cells and inferior olive neurons die due to the absence of trophic support from their main postsynaptic target. We report here that the levels of three independent cell cycle markers--cyclin D, proliferating cell nuclear antigen and bromodeoxyuridine incorporation--are elevated in the granule cells before they die. Although lurcher Purkinje cells die during a similar developmental period, no compelling evidence for any cell cycle involvement in this instance of pre-programmed cell death could be found. While application of the TUNEL technique (in situ terminal transferase end-labeling of fragmented DNA) failed to label dying granule cells in either mutant, light and electron microscopic observations are consistent with the interpretation that the death of these cells is apoptotic in nature. Together, the data indicate that target-related cell death in the developing central nervous system is associated with a mechanism of cell death that involves an apparent loss of cell cycle control.