Program-level predictors of antipsychotic medication adherence among parolees

This study examined the impact of three program-level factors (coercion level, type of antipsychotic prescribed, and guardian supervision) on antipsychotic medication adherence among parolees mandated to an outpatient psychiatric clinic. Overall, 70.7% of the participants tested positive for their prescribed antipsychotic. Older patients were more likely to test positive for their prescribed antipsychotic than younger patients, and African American patients (relative to all other race/ethnic groups) were less likely. With regard to program-level factors, perceived coercion was not significantly associated with medication adherence. However, being prescribed an atypical antipsychotic and having a guardian were independently associated with increased adherence, and combined, these two factors were associated with nearly a tenfold increase in the likelihood of patients testing positive for their prescribed antipsychotic agent, relative to patients who were prescribed conventional antipsychotics and were not under guardian supervision.     

Postmortem atropine concentrations in resuscitation cases

The medications used during resuscitation are often in and of themselves toxic. Several reports have been published regarding toxicities of these drugs, including lidocaine, procainamide, and atropine. But how does a forensic pathologist or toxicologist differentiate a possible intoxication from therapeutic or resuscitory use especially given that the concentrations of such drugs, when used in the setting of resuscitation, have not been studied? Concentrations of a well-known resuscitation medication, atropine, were assessed in cases where it was administered before death during attempted resuscitation in an effort to address this deficiency. A review of deaths occurring in 2009 was undertaken to identify cases where drugs known to be used during resuscitation were present on toxicological analysis. Autopsy reports and medical records were examined to determine how much atropine was administered, the timing and route of administration, the time the sample was drawn (antemortem and postmortem), the source of the sample, and the ultimate cause of death. Eighty-nine cases were identified in which atropine was given before death during attempted resuscitation and was detected in the blood on postmortem toxicological screening; 11 cases were identified in which atropine was administered before death yet was not detected on the postmortem toxicological screening. Mean age was 41 years, and there were 65 males and 35 females. The overall median dose of atropine given was 3 mg, the median difference between the time of last administration of the atropine to the time of death (or draw for antemortem samples) was 15 minutes, and the median atropine concentration was 0.1 mg/L. Analysis failed to reveal significant differences in the atropine concentration based on the route of administration (intravenous or intraosseus), the cause of death, or the time since administration (within the first 2 hours). Analysis did reveal a difference between the atropine concentrations in peripheral versus central blood sources and with prolonged postmortem interval (>24 hours) suggesting postmortem redistribution.     

Patients' rights. Final rule

This final rule amends Department of Veterans Affairs (VA) medical regulations to update the patients' rights regulation by bringing its provisions regarding medication, restraints, and seclusion into conformity with current law and practice. The changes are primarily intended to clarify that it is permissible for VA patients to receive medication prescribed by any appropriate health care professional authorized to prescribe medication, and that it is permissible for any authorized licensed health care professional to order the use of restraints and seclusion when necessary. The rule also makes nonsubstantive changes in the patients' rights regulation for purposes of clarification.     

Clozapine--a dangerous drug in a clozapine-naïve subject

Clozapine is a uniquely effective antipsychotic, but is very toxic in clozapine-na?ve subjects. A 34-year-old male patient in a mental health facility, who was not prescribed clozapine, took 350 mg clozapine obtained from another patient at night. He was found dead the next morning. The presence of cardiomegaly related to obesity may have increased the risk of suffering an acute cardiac event after ingestion of clozapine. The medication prescribed to the patient was not thought to have contributed to the fatal outcome. Post mortem femoral blood clozapine and norclozapine concentrations were 0.48 and 0.20mg/L, respectively. By way of comparison, audit of 104,127 plasma samples (26,796 patients) assayed for therapeutic drug monitoring purposes 1993-2007, showed plasma clozapine 0.35 mg/L or more in 57.5% samples (8.4% 1mg/L or more). Those involved in the investigation of clozapine-associated deaths need to be aware that that death in an adult may occur after a single 'therapeutic' dose. A diagnosis of fatal clozapine poisoning cannot be made solely on the basis of a post mortem blood clozapine measurement.     

Subjective responses and excretion patterns of dextroamphetamine after the administration of therapeutic doses.

Twelve male medical and graduate students received dextroamphetamine sulfate in doses of 0, 5, 10, and 15 mg/70 kg body weight. The study was conducted in a double-blind manner, and treatments were assigned according to randomized, complete block design. The drug was given orally and subjects were instructed not to eat 3 1/2 h prior to administration. After administration, total urine output was collected for 12 h; no attempt was made to control urinary pH to more realistically approach the general clinical usage of amphetamines. The urine was pooled into two 6-h segments and analyzed for amphetamine concentration. Subjective impressions of the treatments were also evaluated by means of the Cornell Medical Index Questionnaire. Results showed that approximately 30% of the total dose was excreted unchanged within 12 h after administration. The amount excreted agreed very closely with the doses given and paralleled the scores for subjective impressions by the subjects. None of the subjects felt that their driving would be impaired for any of the doses administered. This study indicates that under ordinary conditions (in which pH is not artificially controlled), therapeutic doses of dextroamphetamine can be detected in urine for up to 12 h after oral administration.     

Quantitation of atenolol, metoprolol, and propranolol in postmortem human fluid and tissue specimens via LC/APCI-MS

Hypertension is a growing medical concern in the United States. With the number of Americans suffering from hypertension increasing, the use of antihypertensives such as beta-blockers is increasing as well. In fact, three beta-blockers - atenolol, metoprolol and propranolol - were among the 200 most prescribed medications in the United States in 2003. Pilots that successfully manage their hypertension can remain certified to fly. The Federal Aviation Administration currently designates approximately 8% of active pilots as "hypertensive with medication". The Civil Aerospace Medical Institute (CAMI) performs toxicological evaluation on victims of fatal aviation accidents. At CAMI beta-blockers are analyzed using gas chromatography with mass spectrometric detection. We have, however, recently developed a liquid chromatography with mass spectrometric detection (LC/MS) method for the simultaneous quantitation of three commonly prescribed beta-blockers, atenolol, metoprolol and propranolol. One advantage of our LC/MS method is the specificity provided by an ion trap MS. Utilizing an ion trap MS, we were able to conduct MS/MS and MS/MS/MS on each analyte. This method also eliminates the time-consuming and costly derivitization step necessary during GC/MS analysis. Additionally, by utilizing this novel method, any concerns about beta-blocker metabolite and/or sample matrix interference are eliminated. The limits of detection for this method ranged from 0.39 to 0.78 ng/mL and the linear dynamic range was generally 1.6-3200 ng/mL. The extraction efficiencies for each analyte ranged from 58% to 82%. This method was successfully applied to postmortem fluid and tissue specimens obtained from victims of three separate aviation accidents.     

Medication noncompliance in schizophrenia: codification and update

Risk of relapse and recidivism makes the failure to take antipsychotic medication as prescribed a significant issue in forensic psychiatry. This question may arise in such contexts as the setting of bail, plea bargaining, the insanity defense, and sentencing. We have reviewed the literature on medication noncompliance in schizophrenia and present here the results, organized by topics relevant for the work of forensic mental health experts. Reported rates of noncompliance vary widely, reflecting major differences in the populations studied and the methods used as well as the complexities involved in defining noncompliant behavior. A noncompliance rate of 50 percent has been attributed globally to chronic patients, both medical and psychiatric. The tendency of significant factors to interact precludes a simple typology of noncompliance. However, environmental security and supportiveness correlate positively with adherence; whereas anxiety, paranoia, grandiosity, depression, and side effects correlate negatively. Clinicians' assessments of whether medication is being taken have proven to be unreliable. Although monitoring by chemical measurement, particularly a radioreceptor assay for urine samples, can be useful, depot injection ensures that prescribed medication is being taken. Less invasive means of promoting compliance are described; psychodynamic and ethical issues to be considered in the monitoring and promotion of compliance over extended time periods are presented. We also probe the link between medication noncompliance and behavioral relapse. The time between default and relapse is most often measured in weeks. Whether due to medication withdrawal or not, the relapse pattern of each individual tends to repeat, allowing its recognition before recidivism occurs. Restarting medication at this stage, especially with a dosage increase, is usually effective. In sum, the forensic mental health expert can now readily use a large and diverse literature to assist with a variety of significant issues.     

The statistical variability of blood alcohol concentration measurements in drink-driving cases

Like many other places in the world, Hong Kong has drink-driving legislation which prohibits a driver from having in his blood alcohol exceeding a prescribed limit while in control of a motor vehicle. The accuracy of measuring this alcohol concentration is obviously of prime concern as an erroneous result can avert the administration of justice. The common practice is to deduct all errors from the measured value and compare the deducted value with the prescribed limit, so that the benefit of all errors of the measurement is given to the driver. It is therefore important for any laboratory responsible for measuring blood alcohol concentrations to identify and quantify all errors associated with the measurement. The present study examined 900 blood alcohol determinations carried out by the Hong Kong Government Laboratory (HKGL) on cases of suspected drink driving. The determinations were performed by 5 different analysts with two different sets of instruments during 1995-1997. Statistical analysis indicated that the instruments had no bearing on the random error or variability and that even though analyst was a significant factor on variability, the deviation from the mean so caused was only 0.3% and of no practical significance. When the systematic error introduced by the tolerance limits of the certified alcohol standards (purchased from the Laboratory of Government Chemists, UK) was taken into account, the total uncertainty (random plus systematic errors) of an alcohol determination at 99.5% confidence level was found to be 4%. It is recommended that laboratories engaged in blood alcohol determination should adopt similar statistical treatment of their analytical results to find out the error and to ensure that the results are independent of analyst and instrument used.     

Role of drugs and alcohol in impaired drivers and fatally injured drivers in the Strathclyde police region of Scotland, 1995–1998

During the 4-year study period, 1995–1998, the Department of Forensic Medicine and Science, University of Glasgow received a total of 752 biological samples from drivers suspected of driving under the influence of drink and/or drugs in the Strathclyde region of Scotland. The majority of samples were blood and had been primarily obtained from males. Drugs were detected in 68 and 90% of blood and urine samples, respectively. Toxicological analyses revealed that cannabis was the most frequently encountered illegal drug which was detected in 39% of all drug positive blood samples. Benzodiazepines were detected in the majority of drug positive samples with 82% containing at least one member of this group. Polydrug use was prevalent, with the average number of drugs detected per sample increasing from 2.0 in 1995 to 3.1 in 1998. For comparison, the results of toxicological analyses from 151 fatally injured drivers are described. Although the majority of samples tested negative for the presence of drugs and alcohol, drugs were found to be present in 19% and alcohol was detected in 33%. As the majority of drugs had been prescribed or administered post-accident, this study shows that alcohol was the main causative factor conducive to fatal road traffic accidents.     

Simultaneous determination of thirteen beta-blockers and one metabolite by gradient high-performance liquid chromatography with photodiode-array UV detection

A new rapid and sensitive high-performance liquid chromatography (HPLC) method has been developed for the simultaneous identification and quantification in human plasma of the 13 most commonly prescribed beta-blockers and one active metabolite-atenolol, sotalol, diacetolol, carteolol, nadolol, pindolol, acebutolol, metoprolol, celiprolol, oxprenolol, labetalol, propranolol, tertatolol and betaxolol. It involves liquid-liquid extraction procedures followed by liquid chromatography coupled to photodiode-array UV detection with a fixed wavelength at 220 nm for quantification. Compounds were separated on a 5 microm Hypurity C(18) (ThermoHypersil) analytical column (250 mm x 4.6 mm, i.d.) using a gradient of acetonitrile-phosphate buffer pH 3.8 at a flow rate of 1.0 ml/min. The total analysis time was 26 min per sample. Extraction recoveries were between 74 and 113% for the polar compounds and between 20 and 56% for the most apolar compounds. Calibration lines were linear in the range from 25 to 1000 ng/ml for all compounds excepted carteolol and nadolol (50-1000 ng/ml), all of them with coefficients of determination (r2 values) >/=0.994. Limits of detection (LODs) ranged from 5 to 10 ng/ml. Intra-assay and inter-assay precision and accuracy were studied at two concentration levels (100 and 500 ng/ml). The intra-assay coefficients of variation (CVs) for all compounds were 相似文献   

Physical restraint in polish psychiatric facilities

Physical restraint in the form of direct force, forced feeding and medication, mechanical restriction of bodily movement, or the threat of force was administered to close to 30% of patients admitted and hospitalized for a period of at least fourteen days. In transporting the patient to the admission room and then to his treatment ward, the dominant form of restraint used was direct force, or the threat of such force. During the following fourteen days of hospitalization, mechanical restraint and forced medication predominated. Restraint was applied most often, across each of the four phases of the study, to patients deemed dangerous to self or others. This relationship became significantly stronger as the period of hospitalization continued. Across the four phases, patients who protested their hospitalization were more likely to be restrained than patients who agreed to it or who did not object. During each of the four phases of the study, numerous patients who did not object to their hospitalization and who were not deemed dangerous were nevertheless subjected to restraint. The pervasiveness of physical restraint, the wide inter-hospital differences in its use, the apparent over-prediction of patient dangerousness, and the use of restraint with patients who were not deemed dangerous and who did not object to their hospitalization, confirms the need for legal and ethical regulation of physical restraint of psychiatric patients.     

Determination of tramadol in hair using solid phase extraction and GC-MS

Tramadol is a centrally acting synthetic analgesic with mu-opioid receptor agonist activity, it is a widely prescribed analgesic used in the treatment of moderate to severe pain and as an alternative to opiates. Tramadol causes less respiratory depression than morphine at recommended doses. Its efficacy and low incidence of side effects lead to its unnecessary prescribing in patients with mild pain. Tramadol was classified as a "controlled drug" long after its approval for use in Jordan. Analysis of drugs of abuse in hair has been used in routine forensic toxicology as an alternative to blood in studying addiction history of drug abusers. A method for the determination of tramadol in hair using solid phase extraction and gas chromatography-mass spectrometry (GC-MS) is presented, the method offers excellent precision (3.5-9.8%, (M)=6.77%), accuracy (6.9-12%, M=9.4%) and limit of detection 0.5 ng/mg. The recovery was in the range of 87-94.3% with an average of 90.75%. The calibration curve was linear over the concentration range 0.5-5.0 ng/mg hair with correlation coefficient of 0.998. The developed method was tested on 11 hair samples taken from patients using tramadol as prescribed by their physician along with other different drugs in treating chronic illnesses. Tramadol was detected in all hair samples at a concentration of 0.176-16.3 ng/mg with mean concentration of 4.41 ng/mg. The developed method has the potential of being applied in forensic drug hair testing. In Jordan, hair drug testing started to draw the attention of legal authorities which stimulated forensic toxicologists in recent years to develop methods of analysis of drugs known or have the potential to be abused.     

The statistical variability of blood alcohol concentration measurements in drink–driving cases

Like many other places in the world, Hong Kong has drink–driving legislation which prohibits a driver from having in his blood alcohol exceeding a prescribed limit while in control of a motor vehicle. The accuracy of measuring this alcohol concentration is obviously of prime concern as an erroneous result can avert the administration of justice. The common practice is to deduct all errors from the measured value and compare the deducted value with the prescribed limit, so that the benefit of all errors of the measurement is given to the driver. It is therefore important for any laboratory responsible for measuring blood alcohol concentrations to identify and quantify all errors associated with the measurement. The present study examined 900 blood alcohol determinations carried out by the Hong Kong Government Laboratory (HKGL) on cases of suspected drink driving. The determinations were performed by 5 different analysts with two different sets of instruments during 1995–1997. Statistical analysis indicated that the instruments had no bearing on the random error or variability and that even though analyst was a significant factor on variability, the deviation from the mean so caused was only 0.3% and of no practical significance. When the systematic error introduced by the tolerance limits of the certified alcohol standards (purchased from the Laboratory of Government Chemists, UK) was taken into account, the total uncertainty (random plus systematic errors) of an alcohol determination at 99.5% confidence level was found to be 4%. It is recommended that laboratories engaged in blood alcohol determination should adopt similar statistical treatment of their analytical results to find out the error and to ensure that the results are independent of analyst and instrument used.     

Toxicology and characteristics of fatal oxycodone toxicity cases in New South Wales, Australia 1999-2008

All cases of fatal oxycodone toxicity presenting to the New South Wales Department of Forensic Medicine over the period January 1, 1999, to December 31, 2008, were retrieved. A total of 70 cases were identified. The mean age was 48.9 years, 58.6% were men, 21.4% were suicides, and in 30% oxycodone had not been prescribed to the decedent. Injecting drug users constituted 27.1% of cases, and oxycodone tablets were injected immediately prior to death by 21.4%. The mean blood oxycodone concentration was 0.40 mg/L (range 0.06-53.00 mg/L). In all cases, psychoactive substances other than oxycodone were also detected, most frequently hypnosedatives (68.6%), other opioids (54.3%), antidepressants (41.4%), and alcohol (32.9%). Preexisting systemic disease was common: cardiovascular (64.2%), pulmonary (49.3%), hepatic (66.7%), and renal (43.9%).     

Workplace drug testing in a military organization: Results and experiences from the testing program in the Finnish Defence Forces

In the military environment drug abuse is a particular risk for occupational safety. In the Finnish Defence Forces a drug testing program was conducted in 2002–2005; soldiers, professional civilians, and military students were tested when applying for a work or right to study; furthermore, annually 5% of the personnel were subjected to random testing. In total, over 2000 urine samples were analyzed in an accredited laboratory for cannabis, opiates, amphetamines, or cocaine. In this article, the drug testing program as a part of the anti-drug strategy of the Finnish Defence Forces is described, and the findings including practical experiences and financial expenses are reported. Only one person applying for a civilian post tested positive for amphetamine and cannabis. In seven other samples codeine and morphine were detected; these were, however, due to prescribed medication, not drug abuse. In the execution of the program, no particular difficulties were reported. In conclusion, it seems that the use of illicit drugs in the Finnish military is extremely rare, at least partly due to the successful anti-drug strategy. After an elaborate planning, even an extensive drug testing program can be executed without substantial setbacks. In the future, the effectiveness of drug testing programs as a means of improving occupational safety needs to be investigated in controlled studies using comparative design.     

Suicides in the young people of Geneva, Switzerland, from 1993 to 2002

Suicides in Geneva in those less than 25 years old, from 1993 to 2002, were reviewed. Scenes investigations, autopsy findings, toxicology results, and psychiatric history (when available) were examined. There were 65 cases. The average annual suicide rate was 11/100,000. Seventy-seven percent were male, and 23% were female. The youngest was 12 years old and most of the victims were 18 years old and over (89%). For men, the use of firearms was the most common method (38%), followed by fall from height (16%) and drowning (10%). For women, fall from height was the most frequent (40%), followed by firearms and medication overdoses (20% each), hanging (13%), and drowning (7%). Toxicological analysis was performed in 41% of the cases and showed that alcohol was present in 26% and other drugs in 67% of these cases. The most common drugs present were benzodiazepines, cannabis, and cocaine.     

Stereoselective analyses of selegiline metabolites: possible urinary markers for selegiline therapy

The stereoselective analysis of selegiline metabolites in human urine and plasma by gas chromatography using the chiral column with the non-chiral reagent was investigated for the differentiation of selegiline therapy from the methamphetamine (MA) abuse. This method gave clear separations of MA and amphetamine (AM) isomers without any artifactual optical-opposite peaks due to the reagent. After the administration of selegiline tablets, desmethylselegiline (DMS), MA and AM were observed as (−)-isomers in the urine and plasma. Within the first 48 h after dosing, approximately 40% of selegiline administered was excreted in urine as these three metabolites. The parent drug, selegiline, was not detected in any urine or plasma samples. On the other hand, MA and AM were observed only as (+)-isomers in the urine of MA abusers. For the distinction of selegiline users from street MA abusers in urinalysis, (−)-DMS, a specific metabolite of selegiline, was not a suitable marker. (−)-DMS rapidly disappeared from urine and was excreted only 1% of the given dose. By the moment analysis with the trapezoidal integration, the mean residence times of (−)-DMS in plasma and urine were 2.7 and 3.8 h, respectively, which were 5–20 times shorter than those of (−)-MA or (−)-AM. The values of AM/MA in the urine increased from 0.24 to 0.67 (r=0.857) along with time after the selegiline administration. This ratio was not a sufficient marker to differentiate selegiline users from MA abusers, although the values of AM/MA in 74% of MA abusers were less than 0.24. The present GC technique improved the chiral analyses of MA and AM. This chiral analysis is the most useful technique to avoid the misinterpretation in the discrimination between clinical selegiline therapy and illicit MA use.