Biomedical subjects

Ree Dawson

Publications and source records attributed to Ree Dawson.

9 recordsLinked to original sources

PubMed2006

Adaptive strategies for treating childhood mania.

The conduct of trials in children is beset with special difficulties associated with the dearth of treatment data, the considerable heterogeneity of pediatric patient populations connected with (for example) developmental stage, and the strong desire of parents to see that children are provided with the best possible care at all times. To address these issues, we propose the adaptive treatment strategy (ATS) study in which medication changes are adaptively determined according to the evolving treatment response of the individual child. To formalize this methodological approach, we parameterize an ATS as a "threshold" decision rule that monitors whether the patient's response trajectory crosses some threshold of failure. In this formulation, the threshold represents a priori judgments about when to give up on response to medication, and the goal is to find the right response thresholds for continuation, augmentation, or switching. Our exposition is developed in the specific clinical context of childhood mania to maximize accessibility of the ideas but applies more generally to other chronic mental and physical health disorders that are difficult to treat.

Adolescent↗

PubMed2005

Do patients' beliefs act as barriers to effective pain management behaviors and outcomes in patients with cancer-related or noncancer-related pain?

PURPOSE/OBJECTIVES: To understand the role of patients' beliefs in pain management in a cancer population treated in a primary care setting. DESIGN: Secondary analyses of data from the baseline phase of a randomized study. SETTING: Eight of the largest primary care clinics in a managed care system. SAMPLE: 342 patients with cancer who reported pain that would not dissipate on its own or when treated by over-the-counter medication; approximately half had pain that was not cancer related. METHODS: Telephone interviews. MAIN RESEARCH VARIABLES: Patients' demographic characteristics, self-reported history and beliefs about pain and pain treatment, willingness to report pain and take pain medication, recent pain intensity, and administrative data on opioid prescriptions. FINDINGS: Patients' beliefs were not associated strongly with reporting pain or taking medication. Regression analyses revealed that patients' beliefs played a limited role in predicting recent pain intensity, whereas the providers' pain management practices seemed to have a far greater predictive role. Additionally, among patients with recent moderate to severe pain, the relationship between patients' beliefs and their history of pain and pain treatment further suggests that beliefs are likely to be formed, in part, as a consequence of the care they receive. Results did not depend on whether the cause of pain was related to cancer. CONCLUSION: Patients' beliefs were important barriers to effective pain management, either as direct or indirect determinants of pain. Providers' pain management practices were more likely to determine the level of pain relief achieved and the beliefs their patients came to hold based on their personal experiences. IMPLICATIONS FOR NURSING: Nursing interventions should examine the impact of evaluating patients' beliefs in conjunction with pain assessment on pain-related behaviors and pain relief, as well as the ability of patient educational efforts to strengthen accurate beliefs and enable patients to assert themselves when interacting with less knowledgeable providers.

Age Factors↗

PubMed2004

Placebo-free designs for evaluating new mental health treatments: the use of adaptive treatment strategies.

The dominant pre-marketing clinical trial in psychopharmacology is a non-equivalence design that randomizes patients to one of three treatments: an accepted standard, the innovation (new drug), or placebo, with the main efficacy comparison being innovation vs placebo. The reasons behind the choice of placebo control in new drug development include anticipated small effect size for active-controlled comparisons and the sufficiency of demonstrated treatment effect (new drug vs placebo) for regulatory approval. These reasons have led to great reliance on placebo control in drug evaluation studies, despite the ethical controversy over the use of placebo when there are known effective standard treatments. While the use of placebo controls has been widely debated, a less considered aspect of the usual placebo-controlled non-equivalence design is the disparity between the decisions that it supports and those that pervade clinical practice. We propose an alternative approach that randomizes one group of patients to an adaptive treatment strategy that exemplifies the adaptive nature of clinical decision-making in the treatment of ongoing mental health disorders. The basic idea is to compare the adaptive strategy, which uses a patient's outcomes to date to determine when to switch from an initial treatment (e.g. an accepted standard) to an alternative (e.g. the new) treatment, to fixed trials of either treatment option. We state the conditions under which the adaptive treatment RCT is attractive to implement and the requirements for doing so.

Antipsychotic Agents↗

PubMed2004

Clozapine reduces alcohol drinking in Syrian golden hamsters.

Alcohol abuse contributes substantially to the overall morbidity of schizophrenia. While typical antipsychotic medications do not limit alcohol use in patients with schizophrenia, emerging data suggest that the atypical antipsychotic clozapine does. To further elucidate the effects of these antipsychotics on alcohol use, we initiated a study in alcohol-preferring rodents. Syrian golden hamsters were given free-choice, unlimited access to alcohol. Nine days of treatment (s.c. injection) with clozapine (2-4 mg/kg/day), but not haloperidol (0.2-0.4 mg/kg/day), reduced alcohol drinking. Clozapine reduced alcohol drinking by 88% (from 11.3+/-1.7 to 1.4+/-0.2 g/kg/day) while increasing both water and food intake. Alcohol drinking gradually (during 24 days) returned toward baseline in the clozapine-treated animals when vehicle was substituted for clozapine. Further increasing the doses of haloperidol (0.6-1.0 mg/kg/day) had no effect on alcohol drinking; moreover, very low doses of haloperidol (0.025-0.1 mg/kg/day) tested in separate groups of hamsters also had no effect on alcohol drinking. This study demonstrates that clozapine, but not haloperidol, can effectively and reversibly decrease alcohol consumption in alcohol-preferring hamsters. The results are compatible with the observations that clozapine, but not haloperidol, limits alcohol use in patients with schizophrenia. These data further suggest that clozapine may serve as a prototype for developing novel treatments for alcohol abuse.

Alcohol Drinking↗

PubMed2004

Dynamic treatment regimes: practical design considerations.

BACKGROUND: Clinical management of chronic disease requires a dynamic treatment regime (DTR): rules for choosing the new treatment based on the history of response to past treatments. Estimating and comparing the effects of DTRs from a sample of observed trajectories of treatment and outcome depends on the untestable assumption that new treatments are assigned independently of potential future responses to treatment, conditional on the history of treatments and response to date ("sequential ignorability"). In longitudinal observational studies, sequential ignorability must be assumed, while randomization of dynamic regimes can guarantee it. METHODS: Using several clinical examples, we describe the simplest randomized experimental designs for comparing DTRs. We begin by considering an initial treatment A and a second treatment B, and discuss how a dynamic treatment regime that starts with A and leads (sometimes) to B, might be compared to either fixed treatment A or B. We also illustrate the problem of finding the optimal sequence of treatments in a DTR, when there are several choices. We describe and contrast two ways of incorporating randomization into studies to compare such regimes: baseline randomization among DTRs versus randomization at the decision points (sequentially randomized designs). CONCLUSIONS: We discuss estimation and inference from both baseline randomized and sequentially randomized designs and conclude with a discussion of the differences between the experimental and observational approaches to optimizing and comparing dynamic treatment regimes.

Chronic Disease↗

PubMed2003

Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone.

BACKGROUND: Alcohol and cannabis use disorders worsen the course of schizophrenia. While the typical antipsychotics are of limited value in controlling substance use in schizophrenic patients, previous studies suggest that the novel antipsychotic clozapine (CLOZ) may decrease their substance use. We describe a retrospective study of the effects of the novel antipsychotics risperidone (RISP) and clozapine on alcohol and cannabis use in patients with schizophrenia or schizoaffective disorder and comorbid alcohol and/or cannabis use disorder. METHOD: This study involved retrospective assessment of abstinence (cessation of alcohol and cannabis use) in 41 patients treated with either risperidone (n=8) or clozapine (n=33) for at least 1 year. In 32 of these 41 patients, information was available on whether abstinence occurred during the 1-year period. RESULTS: Abstinence rates were significantly higher in patients treated with clozapine than in those treated with risperidone (54% vs. 13%, p=0.05). The nine patients treated for at least 1 year, but excluded from the analysis because time of cessation of use was not known, had all stopped alcohol/cannabis use during clozapine treatment. DISCUSSION: While the limitations of this retrospective study must be recognized, the data suggest that comorbid patients treated with clozapine are more likely to abstain from alcohol and cannabis use than are those treated with risperidone. Further prospective studies will be required to confirm these intriguing results.

Adult↗

PubMed2002

Antipsychotic medication, prolactin elevation, and ovarian function in women with schizophrenia and schizoaffective disorder.

Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactin-elevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (N=6) and normoprolactinemia (N=10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our sample size is small, warranting the need for further investigation, the findings of this preliminary study suggest that antipsychotic-induced hyperprolactinemia, alone, may not adequately explain the observed ovarian dysfunction in women with schizophrenia.

Adult↗

PubMed2002

Using inverse weighting and predictive inference to estimate the effects of time-varying treatments on the discrete-time hazard.

We estimate the effects of non-randomized time-varying treatments on the discrete-time hazard, using inverse weighting. We consider the special monotone pattern of treatment that develops over time as subjects permanently discontinue an initial treatment, and assume that treatment selection is sequentially ignorable. We use a propensity score in the hazard model to reduce the potential for finite-sample bias due to inverse weighting. When the number of subjects who discontinue treatment at any given time is small, we impose scientific restrictions on the potentially observable discontinuation hazards to improve efficiency. We use predictive inference to account for the correlation of the potential hazards, when comparing outcomes under different durations of initial treatment.

Antidepressive Agents↗

PubMed2002

Probing the paradox of patients' satisfaction with inadequate pain management.

The paradox of patients who are in pain, yet satisfied with their pain management, has been previously reported. To probe this paradox, we used cross-sectional data collected in the primary care setting on cancer patients' patterns of pain and pain treatment, beliefs and expectations about pain and pain relief, willingness to report pain and take pain medication, care from the provider, and satisfaction with their pain management (n = 316). Descriptive findings were similar to other studies: more than 75% of patients were satisfied or very satisfied with their overall pain management, despite almost half of all patients reporting recent moderate to severe pain. Univariate and bivariate analyses were consistent with the hypothesis that patients may expect and are therefore satisfied with the "peak and trough" pattern of pain severity that occurs with "as-needed" administration of analgesics. However, multivariate analyses failed to directly support this hypothesis. Instead, regression analyses identified factors related to characteristics of patients' pain experiences, patients' beliefs about pain and its inevitability, the frequency that patients reported their pain, and aspects of the patient--provider relationship. Predictors of patients' satisfaction with how their primary care doctor managed their pain included: whether or not the patient was told that treating pain was an important goal, whether or not the patient reported sustained long-term pain relief, and the degree to which the patient was willing to take opioids if prescribed by the doctor or nurse (adjusted R(2) = 0.22). Qualitative data collected from patients who were in severe pain during the past three days but satisfied with their pain management (n = 88) further suggest the importance of the patient--provider relationship in shaping patient expectations. Based on these findings, we recommend that future research on outcomes in pain management place greater emphasis on the potential impact of the patient-provider relationship.

Aged↗