The -149C>T SNP within the DeltaDNMT3B gene, is not associated with early disease onset in hereditary non-polyposis colorectal cancer.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited syndrome caused by germline mutations in mismatch repair (MMR) genes. HNPCC patients have a lifetime risk of 80% of developing colorectal cancer (CRC); however the likely age of onset is difficult to predict. A single C>T polymorphism located within the promoter region of the DeltaDNMT3B gene has recently been reported to be associated with a significant increase to the risk of early onset CRC. In this study we determined the DeltaDNMT3B genotype in 404 confirmed HNPCC participants (total of 194 CRC cases) from Australia (203) and Poland (201). From the total number of participants there were 194 diagnosed cases of CRC and 210 healthy MMR gene mutation carriers. The study was undertaken to assess whether the reported effect observed in a previous study of 146 HNPCC patients is consistent in a larger separate and unrelated participant cohort. Through the statistical tests of Kaplan-Meier survival analysis and Cox hazard regression models we did not observe any significant association between the DeltaDNMT3B C>T SNP and early onset CRC in HNPCC patients.

"A fool for a client": print portrayals of 49 pro se criminal defendants.

In the United States, an accused person has a constitutionally protected right to serve as his or her own lawyer, even if this means he or she has "a fool for a client." In the current study, information from more than 2,700 articles in the LEXIS "U.S. New, Combined" database was used to produce what the authors believe is the psychiatric literature's first characterization of a group of pro se criminal defendants. The sample's 49 defendants had a broad age range (18-75 years) and a broad range of educational backgrounds (9 to >20 years of formal schooling). Men, attorneys, persons with other advanced degrees, and unemployed persons formed disproportionately large fractions of the sample, compared with the general population. The defendants faced a broad variety of charges; homicide was the most common one. Many had reasonable motives for representing themselves, such as dissatisfaction with their lawyers or believing that they could do as well without attorney representation. Defendants' apparent reasons for representing themselves fell into one of three categories: eccentric (16 defendants), ideological (4 defendants), and personal (19 defendants). These categories offer courts and evaluators three possible conceptualizations of a pro se defendant's behavior, outlook, and motivation.

Intervals for posttest probabilities: a comparison of 5 methods.

BACKGROUND: Several medical articles discuss methods of constructing confidence intervals for single proportions and the likelihood ratio, but scant attention has been given to the systematic study of intervals for the posterior odds, or the positive predictive value, of a test. METHODS: The authors describe 5 methods of constructing confidence intervals for posttest probabilities when estimates of sensitivity, specificity, and the pretest probability of a disorder are derived from empirical data. They then evaluate each method to determine how well the intervals' coverage properties correspond to their nominal value. RESULTS: When the estimates of pretest probabilities, sensitivity, and specificity are derived from more than 80 subjects and are not close to 0 or 1, all methods generate intervals with appropriate coverage properties. When these conditions are not met, however, the best-performing method is an objective Bayesian approach implemented by a simple simulation using a spreadsheet. CONCLUSION: Physicians and investigators can generate accurate confidence intervals for posttest probabilities in small-sample situations using the objective Bayesian approach.

Conventional and atypical antipsychotics and the evolving standard of care.

Novel or atypical antipsychotic medications appear to offer patients the benefits of conventional neuroleptics with lower risks of side effects, but the newer drugs cost much more than the older drugs. Many U.S. psychiatrists have concluded that the novel antipsychotic drugs should be first-line therapy and represent an emerging standard of care in treating psychoses. This view raises the question of whether doctors who prescribe the older, cheaper drugs are engaging in malpractice or violating patients' rights. The authors explore reasons why psychiatrists may continue treating some psychotic patients with conventional neuroleptics, despite the apparent advantages of novel antipsychotics. They also describe possible sources of liability that might arise from using conventional neuroleptics and examine how existing case law might bear on these matters. Recent data on antipsychotic prescription practices and court decisions issued through September 2000 suggest that proper use of the older drugs is not a deviation from the standard of care. However, case law suggests that psychiatrists have a legal obligation to tell patients about novel antipsychotic agents even if they continue to prescribe conventional neuroleptics.

Interpreting clinical evidence of malingering: a Bayesian perspective.

Customary ways of reporting on or testifying about malingering have shortcomings. Stating an opinion "with reasonable medical certainty" tells fact-finders little about how much confidence the opinion deserves; stating that an individual's behavior is similar to that of known malingerers does not convey the information that fact-finders really need to know, which is the likelihood that the evaluee in question is a malingerer, given the evaluator's findings. Mossman and Hart (Mossman D, Hart KJ: Presenting evidence of malingering to courts: insights from decision theory. Behav. Sci. Law 14:271-91, 1996) recommend that mental health professionals address this problem by using Bayes' theorem to interpret test data from evaluations. However, these authors do not discuss the use of evidence obtained during interviews and from other clinical contexts, nor do they describe a method for quantifying imprecision in Bayesian probabilities. This article provides examples of how forensic evaluators might use a Bayesian perspective to interpret clinical indicia of malingering observed during evaluations of adjudicatory competence. The article discusses sources of imprecision in Bayesian posterior probabilities, describes a method for characterizing that imprecision using confidence intervals, and then presents several sample calculations that illustrate how interview findings change the likelihood of malingering. The article also discusses the implications of the Bayesian approach for forensic evaluations and for future research on malingered incompetence.

The meaning of malingering data: further applications of Bayes' theorem.

A previous Behavioral Sciences and the Law article (Mossman & Hart, 1996) asserted that information from malingering tests is best conceptualized using Bayes' theorem, and that courts therefore deserve Bayesian interpretations when mental health professionals present evidence about malingering. Mossman and Hart gave several examples of estimated Bayesian posterior probabilities, but they did not systematically address how one constructs confidence intervals for these estimates. This article explains how the usually imperfect nature of humanly created diagnostic tests mandates Bayesian interpretations of test results, and describes methods for generating confidence intervals for posterior probabilities. Sample calculations show that Bayesian reasoning is quite feasible and would not require investigators to expend unusual efforts when constructing and validating malingering instruments. Bayesian interpretations most accurately capture what malingering tests do: provide information that alters one's beliefs about the likelihood of malingering.

"Hired guns," "whores," and "prostitutes": case law references to clinicians of ill repute.

The "hired gun phenomenon" is a recurrent topic in forensic psychiatric shop talk, but scholars have conducted very little systematic investigation of how courts respond to the suggestion that mental health testimony is "for sale." This article examines the issue using findings from a computer search of court decisions that make, or refer to, derogatory statements concerning mental health experts. The search strategy, using the root words or search terms "(prostitut! or whore or hired gun) w/100 psych!," yielded 567 cases, 45 (7.9%) of which contained comments about professionals' ethics. In 35 opinions, professionals were termed or compared with "hired guns"; five cases described testifying experts using the word "whore," and five cases used some variation on "prostitute." Most cases referred to psychiatrists (rather than psychologists); specific clinicians were identifiable in 26 cases. Over half the remarks occurred in appeals of criminal convictions and concerned psychiatric testimony at trial or before sentencing. Prosecutors were the most common sources of disparaging statements; appellate courts usually disapproved of their remarks but did not reverse convictions. Appellate decisions themselves were the second most frequent sources of derogatory remarks. These findings document the perception among legal professionals that many mental health experts are unscrupulous.

An open trial of olanzapine in patients with treatment-refractory psychoses.

Olanzapine's structural similarities to clozapine and the results of premarketing clinical trials suggested potential usefulness in treating patients with treatment-refractory psychoses. Sixteen inpatients from the state hospital with severe, refractory schizophrenic or schizoaffective psychoses received olanzapine in a prospective, 12-week, open-label trial. The olanzapine dose was 10 mg/day for at least the first 6 weeks and never exceeded 20 mg/day. Mood stabilizers and other antipsychotic agents were discontinued before olanzapine was started. Patients frequently became more agitated within the first several weeks of initiating treatment, requiring the increased use of benzodiazepines and often leading to the discontinuation of olanzapine. Two patients improved significantly. Overall, significant clinical improvement was noted only for motor side effects. This study concluded that olanzapine was not effective in this heterogeneous group with chronic, severe, treatment-resistant psychosis when used in this manner. Further research is needed to explain the tendency toward agitation upon transition to olanzapine, which is reminiscent of reported risperidone complications. Clinicians should be alert for this complication and should minimize concomitant medication changes that might add to the risk of emergent agitation.

Three-way ROCs.

Receiver operating characteristic (ROC) analysis traditionally has dealt with dichotomous diagnostic tasks (e.g., determining whether a disorder is present or absent). Often, however, medical problems involve distinguishing among more than two diagnostic alternatives. This article extends ROC concepts to diagnostic enterprises with three possible outcomes. For a trichotomous decision task, one can plot a ROC surface on three-dimensional coordinates; the volume under the ROC surface (VUS) equals the probability that test values will allow a decision maker to correctly sort a trio of items containing a randomly-selected member from each of three populations. Thus, the VUS summarizes global diagnostic accuracy for trichotomous tests, just as the area under a ROC curve does for a two-alternative diagnostic task. Information gain at points on the surface can be calculated just as is done for two-dimensional ROC curves, and investigators can thus compare three-way ROCs by comparing maximum information gain on each ROC surface.

"Courtroom whores"?--or why do attorneys call us?: findings from a survey on attorneys' use of mental health experts.

Mental health professionals who serve as expert witnesses are repeatedly characterized as (in the words of one recent author) "Whores of the Court." However, scholars have published little systematically gathered data about why attorneys seek mental health opinions and the criteria they use for selecting experts. We investigated these issues using a mailed survey of attorneys and judges. A slight majority of attorney respondents had requested mental health professionals' opinion in the previous year. The most important factors in selecting experts were their knowledge, ability to communicate, and local reputation; national reputation and scholarly writings were least important. Forty-nine percent of the responding attorneys said that receiving a favorable opinion was a "very important" or "essential" consideration, although this did not necessarily mean they wanted a dishonest opinion. Our findings suggest that most forensic work is performed by mental health professionals who are chosen because of their knowledge, communication skills, and local reputations.

A decision analysis approach to neuroleptic dosing: insights from a mathematical model.

BACKGROUND: Although several published studies suggest that little benefit accrues from raising doses of conventional antipsychotic drugs above 500-800 chlorpromazine equivalents per day (CPZeq/day), institutionalized patients with schizophrenia often receive larger doses. Decision analysis could alter this practice by helping clinicians select doses through use of quantitative models that incorporate the consequences of each dose, the likelihood of those consequences, and explicit risk/benefit weightings. METHOD: This study uses representative published data to develop equations and graphs that describe dose-associated likelihoods of treatment response, side effects, and balances between benefits and incidence of side effects. RESULTS: Response rates fit a sigmoid curve that flattens at 500 CPZeq/day; a hyperbolic curve describing side effects reaches a plateau at much higher doses. Combining these curves shows that higher drug doses yield ever diminishing returns, because as the dose increases, the number of side effects per benefited patient also increases. A table and graphs show clinicians how to use these results to critique their current practices and make explicit risk/benefit judgments about dosages. CONCLUSION: Mathematical expressions for dose-related side effect and response rates are potentially useful tools for evaluating low-, intermediate-, or high-dosage neuroleptic treatment regimens.

Sex on the wards: Conundra for clinicians.

Should psychiatric inpatients be allowed to engage in sexual activities? Do clinicians have a right to prevent them from doing so? If so, when may sexual interaction be restricted? What sorts of clinical issues and problems are posed for nursing staff, and how should psychiatrists and administrators respond to these? These and related questions have received little attention from either medical or legal scholars, in sharp contrast to the extensive analysis devoted to other issues affecting the lives of psychiatric inpatients, and in especially sharp contrast to our culture's inundation with media messages about sex. This article summarizes the modest body of scholarship concerning sexual interactions among hospitalized patients, the clinical and administrative questions faced by psychiatrists who work with inpatients, and the potential medicolegal problems that inpatients' sexual activities can create. It concludes with a conceptual framework that clinicians can use to devise solutions to the problems arising from inpatients' sexuality.

Malpractice and the psychiatrist : a primer for residents.

Over the past two decades, the number of malpractice claims filed against psychiatrists has risen steadily, so that about 6% of all psychiatrists are named in new lawsuits each year. Psychiatrists-in-training are just as susceptible to lawsuits as their board-certified colleagues, and psychiatric residents work in settings where the likelihood of events that generate litigation is high. This primer introduces residents to the major issues involved in psychiatric malpractice. The article also discusses aspects of clinical practice that are especially affected by potential malpractice liability and outlines practical methods for limiting vulnerability to adverse malpractice litigation.

Veterans affairs disability compensation: a case study in countertherapeutic jurisprudence.

This article examines the disability compensation programs and health care system of the Department of Veterans Affairs (VA) from the perspective of therapeutic jurisprudence scholarship. VA psychiatric patients have unambiguous financial incentives to endlessly litigate disability claims, to seek lengthy hospitalization rather than outpatient treatment, and to be ill, disabled, and unemployed. These countertherapeutic incentives reward incapacitation, encourage perceiving one-self as sick, diminish personal responsibility, taint treatment relationships, and lead to disparaging perceptions of VA patients. In addition, such perceptions produce moral dilemmas that arise from mutual distrust and frustration when patients and caregivers have antagonistic goals for the clinical encounter. Changes in disability determination procedures, compensation levels, and patterns of payment for treatment could give VA patients and caregivers a "healthier" health care system that encourages personal responsibility and promotes respectful attitudes toward patients. In the absence of such changes, an awareness of countertherapeutic financial incentives can help clinicians distinguish between psychopathological behavior and the pursuit of a rational income strategy, and can help practitioners recognize that apparently deceitful or litigious behavior represents a reasonable response to the economic contingencies that VA patients face.

Resampling techniques in the analysis of non-binormal ROC data.

The methods most commonly used for analyzing receiver operating characteristic (ROC) data incorporate "binormal" assumptions about the latent frequency distributions of test results. Although these assumptions have proved robust to a wide variety of actual frequency distributions, some data sets do not "fit" the binormal model. In such cases, resampling techniques such as the jackknife and the bootstrap provide versatile, distribution-independent, and more appropriate methods for hypothesis testing. This article describes the application of resampling techniques to ROC data for which the binormal assumptions are not appropriate, and suggests that the bootstrap may be especially helpful in determining confidence intervals from small data samples. The widespread availability of ever-faster computers has made resampling methods increasingly accessible and convenient tools for data analysis.

Pulsed electrochemical detection of penicillins using three and four step waveforms.

Aided by the construction of a custom potentiostat, a series of different PAD waveforms were compared to find the optimum detector for penicillin oxidation. The waveforms included standard 3-step direct and indirect PAD in addition to reverse-PAD and 4-step PAD. Two new waveforms, the indirect reverse-PAD and the 4-step indirect PAD were examined in the study. Under the solvent conditions of the study (0.01M acetate buffer, pH 4.6) the indirect waveforms yielded the best detectability for penicillin G while the reverse-PAD waveforms yielded the worst performance. The 4-step PAD methods did not improve detectability when compared to the 3-step types, but they did provide output peak profiles with better shapes and less tailing. Although indirect waveforms gave better detectability than direct detection in the 0.01M acetate buffer solution, the limits of detection for each were found to be differing functions of ionic strength. At higher acetate concentrations, direct PAD was more favorable than indirect detection.