Biomedical subjects

N R Temkin

Publications and source records attributed to N R Temkin.

At least 19 recordsLinked to original sources

PubMed1997

Revised Winter-Tozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia.

OBJECTIVE: To develop a revised equation reflecting the current practice of measuring unbound phenytoin at room temperature, and to evaluate the revised Winter-Tozer method of predicting normalized total phenytoin concentrations in two groups of patients with hypoalbuminemia-elderly nursing home patients and critically ill head trauma patients. DESIGN: Albumin, unbound phenytoin, and total phenytoin concentrations were obtained from two sources: prospectively from a group of elderly nursing home patients and by a retrospective chart review of trauma patients enrolled in a previous double-blind, placebo-controlled study. SETTING: Community nursing homes; a university-affiliated urban teaching hospital. PARTICIPANTS: Elderly nursing home patients (n = 46) taking chronic phenytoin therapy and patients enrolled in a double-blind, placebo-controlled study (n = 58) evaluating the use of phenytoin to prevent posttraumatic seizures. MAIN OUTCOME MEASURES: Prediction error analysis was performed by using the methods proposed by Sheiner and Beal. Bias and precision were evaluated by calculating the mean prediction error (MPE) and root mean squared error (RMSE), respectively. RESULTS: The Winter-Tozer equation consistently overpredicted the normalized phenytoin concentration in the elderly nursing home population (MPE = 3.2, RMSE = 5.9) and the trauma patients (MPE = 3.3, RMSE = 4.8). The equation was revised to reflect the increased protein binding of phenytoin with decreased temperature and resulted in significantly decreased bias in both groups of patients. CONCLUSIONS: The revised equation is useful in predicting normalized phenytoin concentrations in both elderly nursing home patients and critically ill trauma patients.

Adolescent↗

PubMed1995

Alcohol use before and after traumatic head injury.

STUDY OBJECTIVE: To determine (1) the significance of blood alcohol level in the emergency department in history of alcohol abuse and (2) the significance of habitual alcohol use in head-injured patients before and after injury. DESIGN: Inception cohort study with 1-year follow-up. SETTING: Level I trauma center. PARTICIPANTS: One hundred ninety-seven hospitalized adult head-injury survivors with a broad spectrum of head-injury severity. RESULTS: Alcohol use and behavioral problems associated with alcohol use were assayed before injury and in the month and year after injury. The patients' blood alcohol levels in the ED were also examined. Preinjury alcohol abuse was frequent; 42% of the subjects were legally intoxicated while in the ED. The amount of drinking and magnitude of reported preinjury alcohol problems decreased soon after the injury but was followed by an increase by 1 year, although the amount of drinking did not return to the preinjury level (P < .0001). Patients with more severe head injuries decreased their drinking more than did those with less severe head injuries. The patients' blood alcohol levels in the ED were a good indicator of the magnitude of their preinjury alcohol problems (r = .51 to .59; each, P < .001). CONCLUSION: Preinjury habitual alcohol abuse is frequent in head-injured patients. Blood alcohol levels in the ED are indicative of history of problem drinking and might serve as a basis for treatment referral. The first weeks after injury in hospitalized patients may provide an opportunity to begin interventions because head-injured patients drink less at that time.

Adolescent↗

PubMed1995

Classification and regression trees (CART) for prediction of function at 1 year following head trauma.

A cohort of 514 hospitalized head-injury survivors was identified based on their injury and 448 (87%) of them were followed for 1 year. Comprehensive neurobehavioral testing was performed 1 month and 1 year after injury. The authors developed predictions of six neuropsychological and two psychosocial outcomes 1 year after head injury. Prediction trees are presented for verbal IQ, Halstead's Impairment Index, and work status at 1 year. Early predictors of neurobehavioral outcome in survivors are similar to previously reported predictors of mortality. Extent (both depth and length) of coma and age are the medical and demographic variables most predictive of late outcome. Adding 1-month scores substantially improves prediction of neuropsychological variables. The classification and regression tree is a useful technique for predicting long-term outcome in patients with head injury. The trees are simple enough to be used in a clinical setting and, especially with 1-month scores, predictions are accurate enough for clinical utility.

Adolescent↗

PubMed1995

Causes, prevention, and treatment of post-traumatic epilepsy.

Post-traumatic seizures often occur after severe head injury. Acutely, these seizures complicate management of the head-injured patient by increasing intracranial pressure and causing postictal decreases in level of consciousness. In the long term, epilepsy can have a negative effect on the patient's functioning and integration into society. The more severe the head injury, the more likely that post-traumatic seizures will occur. The risk of late seizures exceeds 30% for patients with penetrating head injury, intracerebral hematoma, subdural hematoma, depressed skull fracture, or seizure within the first week after injury. Late post-traumatic seizures are treated the same as any epileptic seizures of the same type. Phenytoin and carbamazepine are effective in preventing seizures in the first week after head injury, but are not effective in preventing late seizures. Both additional antiepileptic drugs and neuroprotective agents that may lessen the damage that leads to seizures are being investigated to determine if they are effective in preventing the occurrence of post-traumatic epilepsy.

Anticonvulsants↗

PubMed1994

Employment following traumatic head injuries.

OBJECTIVE: Determine rates of, and factors predictive of, return to work in patients with civilian traumatic head injuries. DESIGN: Inception cohort study with 1- to 2-year follow-up. SETTING: Hospitalized patients in a level I trauma center. PATIENTS: Three hundred sixty-six hospitalized head-injured subjects who were workers before injury and 95 comparison subjects participated in prospective, longitudinal investigations of employment following head injury. Head-injured and comparison subjects were similar on basic demographics and preinjury employment status. The comparison subjects consisted of patients who sustained traumatic injury to the body but not to the head. MAIN OUTCOME MEASURE: Time taken to return to work following head injury. RESULTS: Survival methodology was used for analysis. Whether patients returned to work and when related to both the characteristics of the injured patients (eg, education, preinjury work history), the severity of head injury and associated neuropsychologic problems, and severity of other system injuries. More precise predictions were possible using the multivariate model. CONCLUSIONS: The present study provides a means of assessing employment potential predictively. This can be useful for clinical and research purposes. The results should be used cautiously and should stimulate discussions of appropriate use of services and resources to meet individual patients' needs.

Adult↗

PubMed1994

Decreased plasma protein binding of valproate in patients with acute head trauma.

1. One hundred and ten plasma samples were obtained from 50 patients treated with valproate for prophylaxis of post-traumatic head injuries. The samples were selected to include a wide range of albumin concentrations and were assayed for free and total valproate concentrations. Valproate binding parameters were determined from the Scatchard equation for one binding site using reweighted least squares analysis. 2. Plasma albumin concentrations were measured in 130 patients with head trauma. They started to decrease immediately after trauma, reaching a minimum at 5-7 days of approximately 24% of baseline value and did not return to normal until 1 month. 3. The free fraction of valproate varied six to seven-fold as albumin concentration ranged from 1.5 to 4.8 g 100 ml-1 (218-696 mumol l-1). The mean association constant for binding (Ka) was 0.008 mumol l(-1) and the mean number of binding sites (N) was 2.0. There values were similar to those reported for valproate in otherwise healthy patients with epilepsy. 4. Because of saturable protein binding of valproate, hypoalbuminaemia may necessitate the monitoring of free valproate concentrations to avoid toxicity when valproate is used in patients with acute head injury.

Acute Disease↗

PubMed1993

Psychosocial recovery after head injury.

Psychosocial recovery after head injury was prospectively examined at 1 and 12 months postinjury in a group of 102 hospitalized adult head-injured patients representing a broad range of head injury severity. For comparison purposes, 102 friend controls were used. Outcome was assessed with a battery of psychosocial measures including the Sickness Impact Profile, the Head Injury Symptom Checklist, and the Modified Function Status Index. The results indicate that head-injury patients experience significant psychosocial problems (eg, ability to return to work, resume leisure activity, concentrate and remember information, feelings of irritability) at both 1 and 12 months postinjury but these difficulties improve over time. Whereas improvements occur in both psychosocial and physical areas of functioning, improvements are greater in the physical area. The nature and extent of difficulties seen vary as a function of head injury severity, and time from injury to observation. Finally, the results suggest that not all problems reported by head-injured patients are solely related to the injury (eg, irritability, anxiety, fatigue, or headaches).

Activities of Daily Living↗

PubMed1993

Electrocorticography in patients with medically intractable temporal lobe seizures. I. Quantification of epileptiform discharges prior to resective surgery.

We studied retrospectively the intraoperative preresection electrocorticograms (ECoGs) of 72 patients undergoing surgery for medically intractable, mostly complex partial, temporal lobe seizures (TLS). Quantification of interictal epileptiform discharges (EDs) detected visually at each electrode location in 2 min recording epochs included computations of ED rates (EDs/min) and cumulative voltages (CuVs) (microV/min). Of 6388 EDs, 81% involved the infratemporal surface, 18% the lateral temporal surface and 1% the orbital frontal area. Forty-eight patients (67%) demonstrated multiple (up to 5 or more), temporally independent foci. Dominant foci in medial and lateral infratemporal locations were about equally common and were significantly more frequent than in lateral temporal locations. Rankings of ED CuVs and rates at individual cortical locations defined 4 areas of "relative interictal cortical epileptogenicity." These were arranged in an orderly pattern with the anterior parahippocampal gyrus and the inferomedial surface of the temporal tip displaying the highest and the lateral temporal and posterior infratemporal cortices showing the lowest propensity to the interictal epileptiform discharge. Individual areas were not characterized by distinct clinical seizure manifestations. Preresection ECoGs provide information on the epileptogenic dysfunction that involves most of the temporal lobe of patients with medically intractable TLS.

Adolescent↗

PubMed1993

Electrocorticography in patients with medically intractable temporal lobe seizures. II. Quantification of epileptiform discharges following successive stages of resective surgery.

We quantified retrospectively the interictal epileptiform discharges (EDs) detected visually in the electrocorticograms (ECoGs) of 42 patients undergoing successive stages of anterior temporal lobectomy for medically intractable temporal lobe seizures (TLS). Following first resection sparing the hippocampus (H) and the parahippocampal gyrus (PHG), EDs were recorded on both structures in all patients and by far exceeded in amount those on residual lateral infratemporal and lateral temporal cortices. Frequently, EDs occurred apparently simultaneously but with opposite polarities on the H and the PHG, but more complex relationships were also evident in most individuals. These features likely reflected abnormal post-synaptic activity generated at different locations and cortical depths within the H, PHG, or both. Quantification of epileptiform activity and the effects of selective anterior hippocampectomy or parahippocampectomy suggested that both the H and PHG had remarkable epileptogenic potential. Levels of epileptiform activity were not significantly different in the H and PHG and in the H of subjects with and without H sclerosis. After final resection, including the amygdaloid nucleus (AN), anterior H and PHG, interictal EDs were present, although markedly diminished, in 35 patients. Postresection foci were significantly less numerous and extensive, and attained smaller maximal voltages, than did foci before and after first resection.

Adult↗

PubMed1992

Long-term treatment with gabapentin for partial epilepsy.

Gabapentin was studied as an open-label 'add-on' antiepileptic drug in 35 patients with partial seizures. Follow-up at 6 months, 12 months, 18 months, and 24 months is reported. There was a trend toward improvement in simple (SPS) and complex partial seizures with it reaching significance for SPS at 12 and 24 months and for the weighted combination of seizures at 3 months. Five of nine patients were subsequently successfully converted to gabapentin monotherapy. Of those five, one is now seizure free and three are significantly improved since baseline. One remains with unchanged seizure frequency compared to baseline, but is experiencing less toxicity than at that time. This long-term observation suggests that the short-term effect demonstrated in blinded studies continues and that indeed some patients with refractory epilepsy can be maintained on gabapentin alone. Based on these findings, double-blind monotherapy trials of this drug are presently being conducted.

Acetates↗

PubMed1991

Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures.

In order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures, 244 subjects were randomized to phenytoin or placebo. They received neurobehavioral assessments at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs. In the severely injured, phenytoin significantly impaired performance at 1 month. No significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year. Patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures. We conclude that phenytoin has negative cognitive effects. This, combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week, raises questions regarding its use for long-term prophylaxis. Our findings do not negate phenytoin's proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs.

Adult↗

PubMed1991

Effect of statistical methodology on normal limits in nerve conduction studies.

Mean +/- 2 standard deviations (SD), which relies on a Gaussian distribution, has traditionally been used to derive normal limits for nerve conduction studies. Our purpose was to examine skew in nerve conduction study (NCS) parameters, and to compare normal limits derived by several alternative methods. We examined 22 NCS parameters from 75 asymptomatic, nondiabetic men (controls). The coefficient of skewness (g1) was significantly positive (P less than 0.10, two-tailed test) in 5 of 8 amplitude and 6 of 8 latency measurements. Transformation reduced g1 in 19 of 22 parameters, and was optimal when g1 was closest to zero. For each measurement, ideal normal limits were defined as mean +/- 2 SD of the optimally transformed data of the control subjects. The percentage of 66 diabetic subjects classified as abnormal by the raw data, but normal by the ideal normal limits, was the positive misclassification rate; while the percentage considered normal by the raw data, but abnormal by the ideal normal limits, was the negative misclassification rate. Mean +/- 2 SD of the raw data produced up to 11% positive misclassifications and 12% negative misclassifications. When the range of observed values was used, up to 6% positive misclassifications and 13% negative misclassifications were found, while the 2.5 or 97.5 percentile values produced up to 10% positive misclassifications and 13% negative misclassifications. We conclude that analyses using the raw data to derive normal limits result in an unacceptable rate of misclassification. Normal limits should be derived from the mean +/- 2 SD of the optimally transformed data.

Aged↗

PubMed1991

Management of head injury. Posttraumatic seizures.

Posttraumatic seizures are relatively common among patients with severe head injuries, with major risk factors being penetrating head wound, hematoma, depressed skull fracture, and, for late seizures, early seizures. Management of late posttraumatic seizures, if they do develop, follows the treatment of patients with epilepsy. Their treatment should be determined by the type of seizure (i.e., partial or generalized) and the individual responsiveness of the patient to drug therapy. Prophylactic administration of antiepileptic drugs to prevent posttraumatic epilepsy has been frequently tried. The data supports a short-term but not a long-term effect of the most commonly used drug, phenytoin. A decision of whether to use prophylaxis, with what, and for how long needs to consider the likely benefit (i.e., the chance of seizures if untreated and the likelihood that the proposed treatment will substantially reduce that chance) and risk (i.e., medical or behavioral adverse effects) of this treatment strategy.

Adult↗

PubMed1990

A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures.

BACKGROUND: Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma. However, previous controlled studies of this practice have been inconclusive. METHODS: To study further the effectiveness of phenytoin (Dilantin) in preventing post-traumatic seizures, we randomly assigned 404 eligible patients with serious head trauma to treatment with phenytoin (n = 208) or placebo (n = 196) for one year in a double-blind fashion. An intravenous loading dose was given within 24 hours of injury. Serum levels of phenytoin were maintained in the high therapeutic range (3 to 6 mumol of free phenytoin per liter). Follow-up was continued for two years. The primary data analysis was performed according to the intention to treat. RESULTS: Between drug loading and day 7, 3.6 percent of the patients assigned to phenytoin had seizures, as compared with 14.2 percent of patients assigned to placebo (P less than 0.001; risk ratio, 0.27; 95 percent confidence interval, 0.12 to 0.62). Between day 8 and the end of year 1, 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures; at the end of year 2, the rates were 27.5 percent and 21.1 percent, respectively (P greater than 0.2 for each comparison; risk ratio, 1.20; 95 percent confidence interval, 0.71 to 2.02). This lack of a late effect could not be attributed to differential mortality, low phenytoin levels, or treatment of some early seizures in patients assigned to the placebo group. CONCLUSIONS: Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury.

Adult↗

PubMed1989

General versus disease-specific measures. Further work on the Sickness Impact Profile for head injury.

Three modifications devised to make the Sickness Impact Profile more sensitive to head injury are evaluated in 202 head-injured and 132 general trauma patients 1 month and 12 months after injury. The modifications consist of adding items, deleting nonapplicable items, and reweighting areas of function. Each of the modifications, and especially all three combined, slightly but significantly improve discrimination of head-injured and comparison subjects and increase correlations with neurologic and neuropsychologic severity indexes. These slight improvements occur more often at 12 months than at 1 month and among those without rather than with pre-existing conditions. No improvements are found in the ability to classify patients into subgroups. The modifications fail to make improvements sufficiently large or consistent to provide a practical advantage over the SIP. The standard SIP provides a reasonable measure of psychosocial functioning following head injury. It relates to head injury and other system injury severity and reflects recovery with time. The SIP score relates to emotional functioning even after injury severity has been taken into account. Until other factors, such as emotional status and responses style, are better controlled, little benefit is likely to be obtained from creating disease-specific psychosocial measures.

Activities of Daily Living↗

PubMed1986

Comparison of alternative outcome measures for antiepileptic drug trials.

Studies to determine the efficacy of antiepileptic drugs often use seizure frequency as an outcome measure. Time to kth seizure (k up to 12) was investigated as an alternative endpoint. Monte Carlo simulations, based on seizure behavior in previous clinical trials, were used to evaluate crossover studies with these endpoints. exhibited the highest power. However, tests on time to the 12th seizure, for a sample size of 50, approached the power of tests on seizure frequency with a sample size of 20. Including patients with less severe epilepsy (two vs four seizures per month) did not change the power of tests on time to the kth seizure and lowered it only moderately for tests on seizure frequency. The simulation methodology presented can be adapted to evaluate other design variations.

Anticonvulsants↗

PubMed1986

Neuropsychologic outcome at one-month postinjury.

Neuropsychologic outcome at one-month postinjury was investigated in a group of 102 adult patients with head injury representing a broad spectrum of severity. A group of friends of the patients with head injury was selected for comparison purposes. A comprehensive battery of measures assessing various abilities determined the adequacy of neuropsychological functions. Results support the following conclusions: head injury is associated with early deficits observable on measures assessing a broad spectrum of functions, ranging from simple to complex and motoric to abstraction skills; use of appropriate control groups is essential for determining head injury related deficits; the degree of neuropsychologic deficits depends on the severity of head injury; and the severity indices of time to following commands and depth of coma relate more closely and systematically to adequacy of one-month neuropsychologic outcome than does retrospectively assessed posttraumatic amnesia.

Adolescent↗

PubMed1984

Cognitive-behavioral treatment of depressed affect among epileptics: preliminary findings.

Controlled study showed skills training for the management of depression in an epilepsy population to be effective. Cognitive-behavioral methods were utilized in a structured learning format with 13 clinically depressed epileptic "students." Significantly greater reductions in dysphoria/depression as measured by the Depression Adjective Checklist and the Generalized Contentment Scale occurred among Ss in the treatment group than among control group Ss. Significant decreases in anger and anxiety/stress and increases in social activities were noted on the Community Adjustment Questionnaire (CAQ). Similar trends were evident on the Beck Depression Inventory and the CAQ depression scale.

Adult↗