Commercialization of BRCA1/2 testing: practitioner awareness and use of a new genetic test.
It was our purpose to determine the characteristics of practitioners in the United States who were among the first to inquire about and use the BRCA1 and BRCA2 (BRCA1/2) genetic tests outside of a research protocol. Questionnaires were mailed to all practitioners who requested information on or ordered a BRCA1/2 test from the University of Pennsylvania (UPenn) Genetic Diagnostics Laboratory (GDL) between October 1, 1995 and January 1, 1997 (the first 15 months the test was available for clinical use). The response rate was 67% of practitioners; 54% (121/225) were genetic counselors, 39% (87/225) were physicians or lab directors. Most physicians were oncologists, pathologists, or obstetrician/gynecologists, but 20% practiced surgery or internal or general medicine. Fifty-six percent (125/225) had ordered a BRCA1/2 test for a patient; most of the rest had offered or were willing to offer testing. Of those who had offered testing, 70% had a patient decline BRCA1/2 testing when offered. Practitioners perceived that patients' fear of loss of confidentiality was a major reason for declining. Nearly 60% of practitioners reported that their patients had access to a genetic counselor, but 28% of physicians who ordered a BRCA1/2 test reported having no such access, despite the GDL's counseling requirement. The proportion of physicians reporting no access to genetic counselors for their patients increased from 22.4% in the first half of the study to 50% in the last half. Many practitioners have an interest in BRCA1/2 testing, despite policy statements that discourage its use outside of research protocols. Practitioner responses suggest that patient interest in testing seems to be tempered by knowledge of potential risks. An apparent increase in patient concern about confidentiality and inability to pay for testing could indicate growing barriers to testing. Although most practitioners reported having access to counseling facilities, perceived lack of such access among an increasing proportion of practitioners indicates that lab requirements for counseling are difficult to enforce and suggests that an increasing proportion of patients may not be getting access to counseling. (+info)
Does vestibular stimulation activate thalamocortical mechanisms that reintegrate impaired cortical regions?
Caloric stimulation induced a transient reversal of multimodal hemispatial cognitive deficits in an 81-year-old woman with an acute left cerebral hemisphere stroke. The patient had unawareness of her right hand (asomatognosia), right-sided visual unawareness (hemineglect), aphasia and right-sided weakness (hemiplegia) prior to the stimulation. Transient improvements in impaired sensory, motor, linguistic and cognitive function developed within 30 s following application of the caloric stimulus and onset of horizontal nystagmus. The effect persisted for 3 min and ceased completely after 5 min. While several recent reports have described the capacity of caloric stimulation to transiently improve or reverse a wide range of attentional, cognitive and motor impairments, most examples are in right-hemisphere-damaged patients with long-standing brain injury. Typically, patients have been tested several months or years after the onset of the deficit. A possible mechanism for the temporary reintegration of multiple cognitive functions in this patient is discussed. (+info)
Audit of patients' awareness of ophthalmic diagnoses.
Providing information to patients about their medical condition and treatment options is important in medical management. To assess patients' knowledge of their ocular disease, prognosis, and treatment a questionnaire based survey was performed. 219 patients selected by random systematic sampling during six months from patients attending general ophthalmic clinics in Selly Oak Hospital, Birmingham, were questioned and 217 questionnaires were analysed. The findings showed that patients' knowledge of their diagnosis depended on their condition: patients with common conditions such as glaucoma and cataract had a better understanding of their condition, its treatment, and prognosis compared with patients with rarer conditions such as retinal detachment or patients with multiple diagnoses. In all, 152 patients (70%) wanted more information about their condition; 49 (23%) did not (although 12 (25%) had attempted to obtain information); and 16 (7%) were undecided. In view of the few patients with a precise understanding of their ophthalmic diagnosis and prognosis and the majority's wish for access to further information, that access needs improvement and different modes of disseminating the information should be implemented. (+info)
Prevalence of insomnia: a survey of the enrollees at five managed care organizations.
The purpose of the study was to assess the prevalence of and factors associated with insomnia among enrollees of managed care organizations (MCOs). A survey was distributed either by mail or during a clinic visit to 7,500 enrollees of five MCOs in the United States. The survey included a sleep questionnaire, demographic questions, and questions about medical encounters and prescription drug use. Three levels of insomnia (none; level I--difficulty initiating or maintaining sleep; level II--insomnia with daytime dysfunction) were defined from the responses. Comorbidities were determined by proxy from prescription drug use reported by respondents. A total of 3,447 survey responses were received, yielding a response rate of 46%. Level I and level II insomnia was reported by 13.5% and 32.5% of the respondents, respectively. Level II insomnia increased with decreasing education, income, and age and was more prevalent in women and non-Caucasians. Insomnia was significantly correlated with all daytime sleepiness and most nighttime disturbances factors. Fifty-two percent of all respondents reported at least one comorbid condition. Respondents with multiple comorbidities reported level II insomnia more frequently than those with no comorbidities. Only 0.9% of clinic visitors were seeing a physician specifically for sleep problems. Of those with level I and level II insomnia, only 5.5% and 11.6%, respectively, were taking prescription medications specifically for sleep problems; 11.2% and 21.4%, respectively, were taking over-the-counter medications for sleep. Insomnia occurs in MCO enrollees at rates comparable to those found in the general population. However, few patients with insomnia are actually being treated for their condition. Proper evaluation, diagnosis, and treatment of insomnia are warranted. (+info)
Tramadol or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy.
Tramadol may cause awareness and EEG activation during anaesthesia. We compared tramadol with morphine, administered during wound-closure, surmising that tramadol may cause earlier awakening, more rapid recovery, less respiratory depression and equivalent pain relief. Forty patients received nitrous oxide-enflurane for abdominal surgery. At wound closure, patients received tramadol 3 mg kg-1 or morphine 0.2 mg kg-1 and end-tidal enflurane concentrations were maintained at 0.5 kPa until skin closure, whereupon anaesthesia was discontinued. Times to spontaneous respiration, awakening and orientation were similar in the two groups, as were blood-gas tensions, ventilatory frequency, pain scores and incidence of nausea. Half of each group required supplementary analgesia during their 90-min stay in the recovery room. P-deletion counts improved more rapidly in the tramadol group. This study confirms previous reports that tramadol did not antagonize the hypnotic effects of volatile anaesthetics. Tramadol, administered during operation, was as effective as morphine in providing postoperative analgesia while permitting more rapid psychomotor recovery. (+info)
Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo.
During wakefulness, neocortical neurons are subjected to an intense synaptic bombardment. To assess the consequences of this background activity for the integrative properties of pyramidal neurons, we constrained biophysical models with in vivo intracellular data obtained in anesthetized cats during periods of intense network activity similar to that observed in the waking state. In pyramidal cells of the parietal cortex (area 5-7), synaptic activity was responsible for an approximately fivefold decrease in input resistance (Rin), a more depolarized membrane potential (Vm), and a marked increase in the amplitude of Vm fluctuations, as determined by comparing the same cells before and after microperfusion of tetrodotoxin (TTX). The model was constrained by measurements of Rin, by the average value and standard deviation of the Vm measured from epochs of intense synaptic activity recorded with KAc or KCl-filled pipettes as well as the values measured in the same cells after TTX. To reproduce all experimental results, the simulated synaptic activity had to be of relatively high frequency (1-5 Hz) at excitatory and inhibitory synapses. In addition, synaptic inputs had to be significantly correlated (correlation coefficient approximately 0.1) to reproduce the amplitude of Vm fluctuations recorded experimentally. The presence of voltage-dependent K+ currents, estimated from current-voltage relations after TTX, affected these parameters by <10%. The model predicts that the conductance due to synaptic activity is 7-30 times larger than the somatic leak conductance to be consistent with the approximately fivefold change in Rin. The impact of this massive increase in conductance on dendritic attenuation was investigated for passive neurons and neurons with voltage-dependent Na+/K+ currents in soma and dendrites. In passive neurons, correlated synaptic bombardment had a major influence on dendritic attenuation. The electrotonic attenuation of simulated synaptic inputs was enhanced greatly in the presence of synaptic bombardment, with distal synapses having minimal effects at the soma. Similarly, in the presence of dendritic voltage-dependent currents, the convergence of hundreds of synaptic inputs was required to evoke action potentials reliably. In this case, however, dendritic voltage-dependent currents minimized the variability due to input location, with distal apical synapses being as effective as synapses on basal dendrites. In conclusion, this combination of intracellular and computational data suggests that, during low-amplitude fast electroencephalographic activity, neocortical neurons are bombarded continuously by correlated synaptic inputs at high frequency, which significantly affect their integrative properties. A series of predictions are suggested to test this model. (+info)
Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats.
The discharge profiles of identified abducens, accessory abducens, and orbicularis oculi motoneurons have been recorded extra- and intracellularly in alert behaving cats during spontaneous, reflexively evoked, and classically conditioned eyelid responses. The movement of the upper lid and the electromyographic activity of the orbicularis oculi muscle also were recorded. Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both trace and delayed conditioning paradigms. Motoneurons were identified by antidromic activation from their respective cranial nerves. Orbicularis oculi and accessory abducens motoneurons fired an early, double burst of action potentials (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation of the supraorbital nerve. Orbicularis oculi, but not accessory abducens, motoneurons fired in response to flash and tone presentations. Only 10-15% of recorded abducens motoneurons fired a late, weak burst after air puff, supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons that generated them also were recorded. The activation of orbicularis oculi motoneurons during the acquisition of classically conditioned eyelid responses happened in a gradual, sequential manner. Initially, some putative excitatory synaptic potentials were observed in the time window corresponding to the CS-US interval; by the second to the fourth conditioning session, some isolated action potentials appeared that increased in number until some small movements were noticed in eyelid position traces. No accessory abducens motoneuron fired and no abducens motoneuron modified their discharge rate for conditioned eyelid responses. The firing of orbicularis oculi motoneurons was related linearly to lid velocity during reflex blinks but to lid position during conditioned responses, a fact indicating the different neural origin and coding of both types of motor commands. The power spectra of both reflex and conditioned lid responses showed a dominant peak at approximately 20 Hz. The wavy appearance of both reflex and conditioned eyelid responses was clearly the result of the high phasic activity of orbicularis oculi motor units. Orbicularis oculi motoneuron membrane potentials oscillated at approximately 20 Hz after supraorbital nerve stimulation and during other reflex and conditioned eyelid movements. The oscillation seemed to be the result of both intrinsic (spike afterhyperpolarization lasting approximately 50 ms, and late depolarizations) and extrinsic properties of the motoneuronal pool and of the circuits involved in eye blinks. (+info)
Awareness during anesthesia: a closed claims analysis.
BACKGROUND: Awareness during general anesthesia is a frightening experience, which may result in serious emotional injury and post-traumatic stress disorder. We performed an in-depth analysis of cases from the database of the American Society of Anesthesiologists Closed Claims Project to explore the contribution of intraoperative awareness to professional liability in anesthesia. METHODS: The database of the Closed Claims Project is composed of closed US malpractice claims that have been collected in a standardized manner. All claims for intraoperative awareness were reviewed by the reviewers to identify patterns of causation and standard of care. Logistic regression analysis was used to identify independent patient and anesthetic factors associated with claims for recall during general anesthesia compared to other general anesthesia malpractice claims. RESULTS: Awareness claims accounted for 79 (1.9%) of 4,183 claims in the database, including 18 claims for awake paralysis, i.e., the inadvertent paralysis of an awake patient, and 61 claims for recall during general anesthesia, ie., recall of events while receiving general anesthesia. The majority of awareness claims involved women (77%), younger than 60 yr of age (89%), American Society of Anesthesiologists physical class I-II (68%), who underwent elective surgery (87%). Most (94%) claims for awake paralysis represented substandard care involving errors in labeling and administration, whereas care was substandard in only 43% of the claims for recall during general anesthesia (P < 0.001). Claims for recall during general anesthesia were more likely to involve women (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 1.58, 6.06) and anesthetic techniques using intraoperative opioids (OR = 2.12, 95% CI = 1.20, 3.74), intraoperative muscle relaxants (OR = 2.28, 95% CI = 1.22, 4.25), and no volatile anesthetic (OR = 3.20, 95% CI = 1.88, 5.46). CONCLUSIONS: Deficiencies in labeling and vigilance were common causes for awake paralysis. Claims for recall during general anesthesia were more likely in women and with nitrous-narcotic-relaxant techniques. (+info)