Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

OBJECTIVE: To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. METHODS: A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. RESULTS: Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. CONCLUSIONS: Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio well within the levels for recent advancements in oncology.

Convergent evolution of health information management and health informatics: a perspective on the future of information professionals in health care.

Clearly defined boundaries are disappearing among the activities, sources, and uses of health care data and information managed by health information management (HIM) and health informatics (HI) professionals. Definitions of the professional domains and scopes of practice for HIM and HI are converging with the proliferation of information and communication technologies in health care settings. Convergence is changing both the roles that HIM and HI professionals serve in their organizations as well as the competencies necessary for training future professionals. Many of these changes suggest a blurring of roles and responsibilities with increasingly overlapping curricula, job descriptions, and research agendas. Blurred lines in a highly competitive market create confusion for students and employers. In this essay, we provide some perspective on the changing landscape and suggest a course for the future. First we review the evolving definitions of HIM and HI. We next compare the current domains and competencies, review the characteristics as well as the education and credentialing of both disciplines, and examine areas of convergence. Given the current state, we suggest a path forward to strengthen the contributions HIM and HI professionals and educators make to the evolving health care environment.

Body mass index following natural menopause and hysterectomy with and without bilateral oophorectomy.

OBJECTIVE: The directional and temporal nature of relationships between overweight and obesity and hysterectomy with or without oophorectomy is not well understood. Overweight and obesity may be both a risk factor for the indications for these surgeries and a possible consequence of the procedure. We used prospective data to examine whether body mass index (BMI) increased more following hysterectomy with and without bilateral oophorectomy compared with natural menopause among middle-aged women. METHODS: BMI was assessed annually for up to 10 years in the Study of Women's Health Across the Nation (SWAN (n=1962)). Piecewise linear mixed growth models were used to examine changes in BMI before and after natural menopause, hysterectomy with ovarian conservation and hysterectomy with bilateral oophorectomy. Covariates included education, race/ethnicity, menopausal status, physical activity, self-rated health, hormone therapy use, antidepressant use, age and visit before the final menstrual period (FMP; for natural menopause) or surgery (for hysterectomy/oophorectomy). RESULTS: By visit 10, 1780 (90.6%) women reached natural menopause, 106 (5.5%) reported hysterectomy with bilateral oophorectomy and 76 (3.9%) reported hysterectomy with ovarian conservation. In fully adjusted models, BMI increased for all women from baseline to FMP or surgery (annual rate of change=0.19 kg m(-2) per year), with no significant differences in BMI change between groups. BMI also increased for all women following FMP, but increased more rapidly in women following hysterectomy with bilateral oophorectomy (annual rate of change=0.21 kg m(-2) per year) as compared with following natural menopause (annual rate of change=0.08 kg m(-2) per year, P=0.03). CONCLUSION: In this prospective examination, hysterectomy with bilateral oophorectomy was associated with greater increases in BMI in the years following surgery than following hysterectomy with ovarian conservation or natural menopause. This suggests that accelerated weight gain follows bilateral oophorectomy among women in midlife, which may increase risk for obesity-related chronic diseases.

Adenomatous polyp with intestinal metaplasia of the esophagus (Barrett esophagus) in a dog.

Multiple endoscopic biopsy specimens of esophageal mucosa were received from a 13-year-old castrated male standard Poodle. The dog was presented for painful swallowing. Endoscopically, the distal aspect of the esophagus was inflamed with a polypoid mass that protruded into the esophageal lumen. Histologically, the stratified squamous epithelium overlying the mass and lining the adjacent esophageal mucosa was replaced by papillary projections covered by columnar epithelium with goblet cells supported by a fibrous stroma. This article reports a case of spontaneous esophageal adenomatous polyp with intestinal metaplasia (Barrett esophagus) and reviews the pathogenesis of esophageal metaplasia and adenocarcinoma.

False-positive mammography and depressed mood in a screening population: findings from the New Hampshire Mammography Network.

BACKGROUND: False positives occur in approximately 11% of screening mammographies in the USA and may be associated with psychologic sequelae. METHODS: We sought to examine the association of false-positive mammography with depressed mood among women in a screening population. Using data from a state-based mammography registry, women who completed a standardized questionnaire between 7 May 2001 and 2 June 2003, a follow-up questionnaire between 19 June 2003 and 8 October 2004 and who received at least one screening mammogram during this interval were identified. False positives were examined in relation to depressed mood. RESULTS: Eligibility criteria were met by 13 491 women with a median age of 63.9 (SD = 9.6). In the study population, 2107 (15.62%) experienced at least one false positive mammogram and 450 (3.34%) met criteria for depressed mood. Depressed mood was not significantly associated with false positives in the overall population [OR = 0.96; 95% confidence interval (CI) = 0.72-1.28], but this association was seen among Non-White women (OR = 3.23; 95% CI = 1.32-7.91). CONCLUSION: Depressed mood may differentially affect some populations as a harm associated with screening mammography.

Anaplastic astrocytoma in the spinal cord of an African pygmy hedgehog (Atelerix albiventris).

A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100.

Entropy as a measure of diversity in an inventory of medical devices.

Quantitative techniques for the measurement of species diversity have been developed in ecological studies. One such technique, based on an entropy measurement, has been applied to the assessment of medical device diversity in large inventories of medical equipment. Using this technique it is possible to identify trends which are not apparent from simple considerations of the total number of devices, or the number of device types. Objective measurements of this type can be used to monitor the progress of planned equipment replacement programmes.

Capacitative calcium entry in testosterone-induced intracellular calcium oscillations in myotubes.

Ca2+ oscillations are one of the most important signals within the cell. The mechanism for generation of Ca2+ oscillations is still not yet fully elucidated. We studied the role of capacitative Ca2+ entry (CCE) on intracellular Ca2+ oscillations induced by testosterone at the single-cell level in primary myotubes. Testosterone (100 nM) rapidly induced an intracellular Ca2+ rise, accompanied by Ca2+ oscillations in a majority of myotubes. Spectral analysis of the Ca2+ oscillations revealed a periodicity of 20.3 +/- 1.8 s (frequency of 49.3 +/- 4.4 mHz). In Ca(2+)-free medium, an increase in intracellular Ca2+ was still observed, but no oscillations. Neither nifedipine nor ryanodine affected the testosterone-induced Ca2+ response. This intracellular Ca2+ release was previously shown in myotubes to be dependent on inositol-1,4,5-trisphosphate (IP3). Intracellular Ca2+ store depletion in Ca(2+)-free medium, using a sarcoplasmic/endoplasmic reticulum calcium ATPase-pump inhibitor, followed by re-addition of extracellular Ca2+, gave a fast rise in intracellular Ca2+, indicating that CCE was present in these myotubes. Application of either testosterone or albumin-bound testosterone induced Ca2+ release and led to CCE after re-addition of Ca2+ to Ca(2+)-free extracellular medium. The CCE blockers 2-aminoethyl diphenylborate and La3+, as well as perturbation of the cytoskeleton by cytochalasin D, inhibited testosterone-induced Ca2+ oscillations and CCE. The steady increase in Ca2+ induced by testosterone was not, however, affected by either La3+ or cytochalasin D. These results demonstrate testosterone-induced Ca2+ oscillations in myotubes, mediated by the interplay of IP3-sensitive Ca2+ stores and Ca2+ influx through CCE.

Calibration of radioactive contamination monitors for practical use in hospitals.

Quantitative assessment of radioactive contamination is a desirable aim in any department using radionuclides. Guidance is available for calibration of contamination monitors with sealed reference sources but the calibrations obtained in this way are of limited practical use. In this work, we examined methods for calibration using radionuclides used in the hospital workplace. Calibration factors (s-1 per Bq.cm-2) were obtained for 99mTc, 131I, 90Y and 89Sr for three types of monitor for a range of contamination areas, and minimum detectable activities were calculated. Of the three detectors evaluated, the Berthold LB122/LB6357F proved the most sensitive for all radionuclides tested. The effect of contamination area was found to be significant; calibration factors for a particular monitor varied by up to a factor of 4 with contamination area, which has important implications, for example in the estimation of skin doses. User departments need to be aware of this variation and how to correct for it.

Nefiracetam improves Morris water maze performance following traumatic brain injury in rats.

Nefiracetam, a pyrrolidone derivative, is a nootropic agent that has facilitated cognitive function in a wide variety of animal models of cognitive dysfunction. The purpose of this study was to investigate the efficacy of the chronic postinjury administration of nefiracetam (DM-9384) in improving cognitive performance following central fluid percussion brain injury in rats. Twenty-four hours following surgical preparation, a sham injury or a moderate fluid percussive injury (2.1 atm) was delivered. Nefiracetam was administered chronically (0 or 9 mg/kg, po, for sham animals and 0, 3, or 9 mg/kg for injured animals) on postinjury days 1-15. Cognitive performance was assessed using the Morris water maze (MWM) on postinjury days 11-15. Chronic administration of 3 and 9 mg/kg nefiracetam attenuated MWM deficits produced by central fluid percussive brain injury. Importantly, the MWM performance of the injured animals treated with 9 mg/kg did not significantly differ from uninjured, sham animals. The 9-mg/kg dose of nefiracetam did not have a positive or negative effect on MWM performance of uninjured animals. The results of the present experiment suggest that a nootropic such as nefiracetam may be an appropriate treatment for trauma-induced cognitive dysfunction.

Cryptic duplication of 21q in an individual with a clinical diagnosis of Down syndrome.

We describe an adult male who was diagnosed with Down syndrome (DS) at 9 months of age, but had repeatedly normal karyotypes until recent mid-resolution chromosome studies showed a possible duplication of 21q22.13 to 21q22.3. The abnormality was investigated using fluorescent in situ hybridization (FISH) studies. These showed hybridization of a whole chromosome paint probe (wcp21, Oncor Coatasome 21) to the entire length of both chromosome 21 homologues and one very large hybridization signal of a cosmid contig probe localized within bands 21q22.13-21q22.2(LSI-21, Vysis) on the ?dup(21q) homologue. CGH analysis identified a ratio of 1.5 for the segment of chromosome 21 involving band 21q22, indicating a gain of part, or all, of the terminal band of chromosome 21. The karyotype was thus defined as 46,XY,?dup(21) (q22.13q22.2).ish dup(21)(LSI-21++,wcp21+). Common DS characteristics in our case and 12 previously reported cases with duplications involving chromosome 21 included mental retardation, fifth finger clinodactyly, open mouth and oblique eye fissures. Transverse palmar creases and congenital heart defects, seen in DS less than 40% of the time, were infrequent. Presence of these features did not appear to depend on the specific portion of chromosome 21 that was duplicated. A review of 18 additional clinical features showed no consistent phenotype-genotype correlations.

The effects of propofol in the area postrema of rats.

UNLABELLED: Propofol has an antiemetic effect that may be mediated by gamma-aminobutyric acid (GABA) influences on the serotonin system, the mechanism of which is not known. We used three techniques, immunohistochemistry, High Performance Liquid Chromatography, and electrophysiology, to define propofol's effects on the rat's brainstem. Paired male Wistar rats received propofol, 20 mg/kg/hr, or Intralipid for 6 h. The brains were then subjected to immunohistochemical analysis of serotonin. In a separate experiment after a propofol or Intralipid infusion, cerebrospinal fluid (CSF) was extracted from the fourth ventricle and analyzed for the amount of serotonin and 5-hydroxyindoleacetic acid. Electrophysiological neuronal recordings were made in the area postrema (AP) in response to propofol with and without a GABA or serotonin antagonist. Results showed that immunohistochemical staining for serotonin in the propofol rats was significantly increased (28 +/- 12%) in the dorsal raphe and decreased in the AP (17 +/- 6%) compared with control. There were no significant changes in the isoflurane-anesthetized animals. Both serotonin and 5-hydroxyindoleacetic acid in the CSF of the fourth ventricle at the level of the AP were significantly reduced by 63% and 36%, respectively. Both propofol and pentobarbital injections reduce AP neuronal activity, but only the propofol response was blocked by bicuculline, a GABA antagonist. We conclude that the reduced levels of serotonin in the AP and the CSF may explain the antiemetic property of propofol. Propofol may also directly act on AP neurons via a GABA(A) receptor to reduce their activity. IMPLICATIONS: Propofol may produce its antiemetic effect by depleting the area postrema of serotonin as well as by a direct gamma-aminobutyric acid-mediated inhibition.

A modified technique for minimal-preparation, resin-retained bridges: four case reports.

The minimal-preparation, resin-retained adhesive bridge may be considered to be an ideal choice of fixed prosthesis to replace a single missing tooth, especially in the anterior maxillary region. The technique is well documented, enjoys a high success rate, and with suitable case selection generally employs a conservative preparation. Other advantages include reduced cost compared with conventional bridges and simplified laboratory and clinical procedures. Its limitations are principally due to occlusal factors, or the presence of unsuitable abutment teeth--for example, those that are extensively restored. Another traditional contraindication is the presence of diastemas, which may limit the potential aesthetic gains. This paper presents a series of case reports which describe an altered technique in order to maintain anterior spacing.

Tectal graft modulation of audiogenic seizures in Long-Evans rat.

Audiogenic seizure (AGS) activity can be induced in the seizure-resistant Long-Evans rat by postnatal priming. This study examined the effects of unilateral lesions of the inferior colliculus (IC) and implantation of tectal grafts on AGS components. Animals were primed with a 10-kHz tone burst at 120 dB on postnatal day 14 and tested for AGS susceptibility on day 28, and then two groups were unilaterally lesioned including animals receiving embryonic day 16-17 grafts of caudal tectum. Subsequently, animals were repeatedly tested for wild running and clonic-tonic convulsion components of AGS. The results demonstrate that unilaterally grafted animals with partial IC lesions showed significant reduction in the incidence of clonus expression with greater terminal uniphasic wild running behavior. These effects were stronger than in animals with comparable unilateral lesions alone. Many neurons in graft cases were in direct contact with host tissues to provide a substrate for tissue interactions previously demonstrated to promote neuron survival and remediate IC functions.

Positive and negative modulation of the GABA(A) receptor and outcome after traumatic brain injury in rats.

Glutamate-mediated excitotoxicity has been shown to contribute to cellular dysfunction following traumatic brain injury (TBI). Increasing inhibitory function through stimulation of gamma-aminobutyric acid (GABA(A)) receptors may attenuate excitotoxic effects and improve outcome. The present experiment examined the effects of diazepam, a positive modulator at the GABA(A) receptor, on survival and cognitive performance in traumatically brain-injured animals. In experiment 1, 15 min prior to central fluid percussion brain injury, rats (n=8 per group) were injected (i.p.) with saline or diazepam (5 mg/kg or 10 mg/kg). Additional rats (n=8) were surgically prepared but not injured (sham-injury). Rats pre-treated with the 5 mg/kg dose of diazepam had significantly lower mortality (0%) than injured, saline-treated rats (53%). Also, diazepam-treated (5 mg/kg) rats had significantly shorter latencies to reach the goal platform in the Morris water maze test performed 11-15 days post-injury. In experiment 2, at 15 min post-injury, rats were given either saline (n=5) or 5 mg/kg diazepam (n=6). Rats treated with diazepam did not differ in mortality from injured rats treated with vehicle. However, rats treated with diazepam at 15 min post-injury had significantly shorter latencies to reach the goal platform in the Morris water maze than injured, vehicle-treated rats. In experiment 3, the post-injury administration of bicuculline (1.5 mg/kg, n=8), a GABA(A) antagonist, increased Morris water maze goal latencies compared to injured animals treated with saline (n=8). These results suggest that enhancing inhibitory function during the acute post-injury period produces beneficial effects on both survival and outcome following experimental TBI.

Detection of viral pathogens by reverse transcriptase PCR and of microbial indicators by standard methods in the canals of the Florida Keys.

In order to assess the microbial water quality in canal waters throughout the Florida Keys, a survey was conducted to determine the concentration of microbial fecal indicators and the presence of human pathogenic microorganisms. A total of 19 sites, including 17 canal sites and 2 nearshore water sites, were assayed for total coliforms, fecal coliforms, Escherichia coli, Clostridium perfringens, enterococci, coliphages, F-specific (F(+)) RNA coliphages, Giardia lamblia, Cryptosporidium parvum, and human enteric viruses (polioviruses, coxsackie A and B viruses, echoviruses, hepatitis A viruses, Norwalk viruses, and small round-structured viruses). Numbers of coliforms ranged from <1 to 1, 410, E. coli organisms from <1 to 130, Clostridium spp. from <1 to 520, and enterococci from <1 to 800 CFU/100 ml of sample. Two sites were positive for coliphages, but no F(+) phages were identified. The sites were ranked according to microbial water quality and compared to various water quality standards and guidelines. Seventy-nine percent of the sites were positive for the presence of enteroviruses by reverse transcriptase PCR (polioviruses, coxsackie A and B viruses, and echoviruses). Sixty-three percent of the sites were positive for the presence of hepatitis A viruses. Ten percent of the sites were positive for the presence of Norwalk viruses. Ninety-five percent of the sites were positive for at least one of the virus groups. These results indicate that the canals and nearshore waters throughout the Florida Keys are being impacted by human fecal material carrying human enteric viruses through current wastewater treatment strategies such as septic tanks. Exposure to canal waters through recreation and work may be contributing to human health risks.

The significance of variations in the angular correction factor in in situ gamma spectrometry.

In situ gamma spectrometry is a powerful method of assessing radioactive contamination in soil. The most widely adopted calibration methodology relates the overall sensitivity of the detector system to the product of three calibration factors: (a) the flux at the detector per unit activity in the ground phi/S(A), (b) the detected count-rate per unit flux incident normally at the detector N0/phi and (c) a correction factor to take into account the angular non-uniformity in response of the detector (Nf/N0). The dependence of the latter factor on the activity distribution with soil depth is generally neglected despite the lack of published evidence to support this. By (i) modelling and (ii) use of published experimental profiles, this work examines the range of Nf/N0 values likely to be encountered in the field. It was found that the use of a fixed angular correction factor is justified given that the maximum errors in the derived activity concentration do not exceed 5% and are far outweighed by other uncertainties.

Chromogranin A inhibits dopamine release from rat striatal slices.

Chromogranin A (CGA), a prohormone and a protein component of endocrine and neural secretory granules, neuritic plaques in Alzheimer's disease and Lewy bodies in Parkinson's disease, inhibited the release of dopamine (DA) from perfused rat striatal slices. Dopamine release was stimulated by a pulse of high potassium (40mM) medium introduced at 20 minutes (K1) and 55 minutes (K2) following equilibration. The ratio of K2/K1 was 0.80+/-0.04 in control tissues, but fell significantly to 0.26+/-0.08 when 100nM purified CGA was added prior to the second potassium pulse. This reduction in DA release was equivalent to that seen when calcium was excluded from the buffer (0.19+/-0.05). Pancreastatin, a centrally active peptide product of CGA, had no effect on stimulated DA release (0.77+/-0.06), although it, as well as the other treatments, did reduce basal DA release. It is likely that the parent molecule itself, CGA, or an as yet unidentified product is responsible for inhibition of K-stimulated striatal DA release.

Risk assessment of waterborne protozoa: current status and future trends.

Throughout the past decade much research has been directed towards identifying the occurrence, epidemiology, and risks associated with waterborne protozoa. While outbreaks are continually documented, sporadic cases of disease associated with exposure to low levels of waterborne protozoa are of increasing concern. Current methodologies may not be sensitive enough to define these low levels of disease. However, risk assessment methods may be utilised to address these low level contamination events. The purpose of this article is to provide an introduction to microbial risk assessment for waterborne protozoa. Risk assessment is a useful tool for evaluating relative risks and can be used for development of policies to decrease risks. Numerous studies have been published on risk assessment methods for pathogenic protozoa including Cryptosporidium and Giardia. One common notion prevails: microbial risk assessment presents interesting complications to the traditional chemical risk assessment paradigm. Single microbial exposures (non-threshold) are capable of causing symptomatic illness unlike traditional chemical exposures, which require a threshold to be reached. Due to the lack of efficient recovery and detection methods for protozoa, we may be underestimating the occurrence, concentration and distribution of these pathogenic micro-organisms. To better utilize the tool of microbial risk assessment for risk management practices, future research should focus in the area of exposure assessment.

Heterotopic ossification as a complication of toxic epidermal necrolysis.

The development of heterotopic ossification (HO) as a complication of toxic epidermal necrolysis (TEN) has not been previously reported. TEN, also known as Lyell's syndrome, is a rare but serious skin disorder that typically occurs after the administration of drugs, especially sulfonamides, barbiturates, phenytoin, and nonsteroidal anti-inflammatory agents. TEN is characterized by the development of large fluid-filled bullae with separation of large sheets of skin. Complications of TEN can include extensive denudation of skin with dehydration and electrolyte abnormalities, gastrointestinal hemorrhage, acute tubular necrosis, secondary infection of denuded skin, pneumonia, bacterial conjunctivitis, keratitis, and septic infarcts of internal organs. We report a case of HO in a patient with TEN after treatment with trimethoprim-sulfamethoxazole. A 49-year-old man developed an erythematous rash, bullae, fever, and extensive skin loss consistent with a diagnosis of TEN. He was intubated for complications of TEN (pneumonia) and maintained on bed rest for several weeks. In addition, he developed HO that resulted in multiple joint contractures. He was treated with aggressive range of motion by physical therapy, surgical resection of the HO followed by radiation to both elbows, right hip, and right knee. Postoperative outpatient rehabilitation enabled improved function in his mobility and activities of daily living. HO is known to occur after spinal cord and brain injuries and burns. It has not been reported to occur after TEN. Our experience with this case suggests that HO may merit inclusion into the list of complications of TEN.