Detecting biomarkers associated with antipsychotic-induced extrapyramidal syndromes by using machine learning techniques.

BACKGROUND: Antipsychotic-associated extrapyramidal syndromes (EPS) are a common side effect that may result in discontinuation of treatment. Although some clinical features of individuals who develop specific EPSs are well defined, no specific laboratory parameter has been identified to predict the risk of developing EPS. METHODS: Three hundred and ninety hospitalizations of patients under antipsychotic medication were evaluated. Machine learning techniques were applied to laboratory parameters routinely collected at admission. RESULTS: Random forests classifier gave the most promising results to show the importance of parameters in developing EPS. Albumin has the maximum importance in the model with 4.28% followed by folate with 4.09%. The mean albumin levels of EPS and non-EPS group was 4,06 ± 0,40 and 4,24 ± 0,37 (p = 0,027) and folate level was 6,42 ± 3,44 and 7,95 ± 4,16 (p = 0,05) respectively. Both parameters showed lower levels in EPS group. CONCLUSIONS: Our results suggest that relatively low albumin and folate levels may be associated with developing EPS. Further research is needed to determine cut-off levels for these candidate markers to predict EPS.

Treatment Decision Regret in Patients Who Develop Periprosthetic Joint Infection and Require Two-Stage Revision Surgery.

BACKGROUND: The decision to proceed with total joint arthroplasty (TJA) can be complex and requires an assessment of potential risks of surgery. Patients who experience the potentially devastating complication of periprosthetic joint infection (PJI) may have a poor outcome and wish they had never elected to have surgery. No study has examined decision regret related to the choice to pursue TJA in patients who develop PJI. METHODS: All patients who were treated for PJI with a two-stage revision at a tertiary academic medical center between 2010 and 2020 were surveyed. Ninety-six patients agreed to answer 12 questions concerning their understanding of their preoperative risk of infection and their level of regret with the decision to pursue index TJA. Patient regret was calculated using the Decision Regret Scale. RESULTS: Seventy-two percent of patients reported that their joint replacement and concomitant infection had a severe ongoing impact on their quality of life, although only 28% of respondents regretted their choice to undergo index TJA, and 65% would undergo TJA again. A higher Musculoskeletal Infection Society outcome stage (typically due to failed treatment) and lower understanding of joint infection were associated with a higher level of regret on the Decision Regret Scale (P < .001). CONCLUSION: Self-reported decisional regret was present in only 1 in 4 patients who underwent arthroplasty despite experiencing a devastating complication, and almost two-thirds of patients with PJI reported they would undergo primary TJA again. Patients who were more informed about infection before TJA experienced less regret when they subsequently developed PJI. LEVEL OF EVIDENCE: III.

"Moving Away From Cancer" Prospective Exercise Trial for Female Rural Cancer Survivors: How Can We Step It Up?

PURPOSE: This prospective trial's objective was to determine feasibility and outcomes of an exercise-based intervention for rural overweight/obese female cancer survivors. MATERIALS AND METHODS: Survivors of endometrial, breast, or ovarian cancer enrolled in a 6-month program of increased aerobic activity (30 minutes daily walking) and strength-training exercises using exercise bands (THERABAND; Akron, OH) with personalized telephone motivational coaching. Baseline demographics, anthropomorphic measurements, quality of life (QOL), fitness, and readiness to adopt exercise changes were assessed; daily steps, band use, and follow-up measurements were assessed at 3 and 6 months. Study completion was modeled using logistic regression. RESULTS: The mean age of the 99 women was 59.9 years, the mean body mass index (BMI) was 35.9 kg/m2, 88.9% were white, and 41.4% reported current exercise. Fifty-five women (55.6%) completed the 6-month program, and 36 (36.4%) completed exercise interventions. Using logistic regression to model study completion, only baseline QOL scores (physical component summary) and mental component summary) remained significant predictors. The mean weight change was a gain (0.88 kg). Higher MCS baseline scores and prior regular exercise predicted continued exercise and increased step counts, whereas higher BMI and baseline sleep predicted decreased QOL. Top walking barriers were feeling unwell and weather; barriers to strength exercises were band dislike and pain. CONCLUSION: The most significant predictor of trial completion and improved exercise outcomes was a higher baseline mental QOL. Motivation, belief in the importance of exercise, and prescribed/monitored exercise regimens were not sufficient; supportive and cognitive behavioral therapy interventions for survivors are needed to sustain uptake.

A Professional Development Course Improves Unprofessional Physician Behavior.

BACKGROUND: In 2008 The Joint Commission issued a Sentinel Event Alert that further defined "behaviors that undermine a culture of safety," stating that "intimidating and disruptive behaviors" can result in medical errors that affect patient care and safety. The American College of Physician Executives found that more than 95% of respondents encountered "disturbing . . . and potentially dangerous" behaviors on a regular basis. The purpose of this study is to evaluate the effectiveness of a professional development program on unprofessional physician behaviors using the B29™, a reliable and valid tool to assess workplace behaviors. METHODS: A pre-post study design was used to measure changes in physicians' unprofessional behaviors using the B29, a 35-item, Web-based survey. The survey is completed as a 360° assessment by peers, colleagues, administrators, and staff, and the physician completes a self-assessment. In most cases, the survey is voluntary. Those who completed both a precourse and a postcourse survey made up a convenience sample or subset of the larger number of physicians who completed the course. RESULTS: Twenty-four of 28 physicians in the study experienced an improvement in professional behavior, demonstrated as a decrease in the number of lowest-rated items. The mean decrease for all 28 physicians was 51.1%. Lowest-rated items improved an average of 53.5% overall. T-scores increased (also improved) for 24 of 28 physicians over the six-month period. CONCLUSION: Unprofessional behavior by physicians, as observed and reported by their peers and colleagues, can be positively modified by a relatively brief education program focused on teaching professionalism.

Mindfulness for healthcare providers fosters professional quality of life and mindful attention among emergency medical technicians.

OBJECTIVE: Emergency medical service (EMS) providers are systematically subjected to intense stimuli in their work that may result in distress and emotional suffering. While it is known that mindfulness-based stress reduction (MBSR) helps to foster well-being in healthcare workers, the effectiveness of MBSR among EMS providers is less understood. We explored the impact of a modified version of MBSR for healthcare workers called Mindfulness for Healthcare Providers (MHP) on reducing distress and promoting wellbeing in EMS providers. METHODS: A one-arm pilot study was conducted. We implemented eight two-and-a-half hour sessions of Mindfulness for Healthcare Providers with an additional day-long retreat at the end. Feasibility, perceived stress, professional quality of life, and trait mindfulness were assessed prior to and after the intervention. The professional quality of life scale includes measures of compassion satisfaction, burnout, and secondary trauma. RESULTS: Fifteen veteran EMS providers enrolled in the course; four participants dropped out. Prior to initiation of the study, no significant differences were revealed between those who did not participate (n = 48) and those who did (n = 11). After the intervention EMS providers endorsed statistically significant increases in compassion satisfaction, trait mindfulness, and decreases in burnout compared to the beginning of the program. These changes were sustained at six months post-completion. No significant changes over time were found for secondary trauma or perceived stress. CONCLUSIONS: To our knowledge, this study is the first to employ Mindfulness for Healthcare Providers in an EMS population and to demonstrate a positive impact on self-reported compassion, trait mindfulness, and burnout in this population. Additional research regarding mindfulness training within EMS populations should be conducted to further understand the relationship between mindfulness and perceived stress over time.

Interpersonal Circumplex Profiles Of Persistent Depression: Goals, Self-Efficacy, Problems, And Effects Of Group Therapy.

OBJECTIVES: We assessed severely and persistently depressed patients' interpersonal self-efficacy, problems, and goals, plus changes in interpersonal functioning and depression during 20 weeks of group therapy. METHOD: Outpatients (32 female, 26 male, mean age = 45 years) completed interpersonal circumplex measures of goals, efficacy, and problems before completing 20 weeks of manualized group therapy, during which we regularly assessed depression and interpersonal style. RESULTS: Compared to normative samples, patients lacked interpersonal agency, including less self-efficacy for expressive/assertive actions; stronger motives to avoid conflict, scorn, and humiliation; and more problems with being too submissive, inhibited, and accommodating. Behavioral Activation and especially Cognitive Behavioral Analysis System of Psychotherapy interventions produced improvements in depression and interpersonal agency, with increases in "agentic and communal" efficacy predicting subsequent decreases in depression. CONCLUSIONS: While severely and persistently depressed patients were prone to express maladaptive interpersonal dispositions, over the course of group therapy, they showed increasingly agentic and beneficial patterns of cognitions, motives, and behaviors.

Are Smoking Cessation Treatments Associated with Suicidality Risk? An Overview.

Risk of suicidality during smoking cessation treatment is an important, but often overlooked, aspect of nicotine addiction research and treatment. We explore the relationship between smoking cessation interventions and suicidality and explore common treatments, their associated risks, and effectiveness in promoting smoking reduction and abstinence. Although active smokers have been reported to have twofold to threefold increased risk of suicidality when compared to nonsmokers,1-4 research regarding the safest way to stop smoking does not always provide clear guidelines for practitioners wishing to advise their patients regarding smoking cessation strategies. In this article, we review pharmacological and cognitive behavioral therapy (CBT) options that are available for people seeking to quit smoking, focusing on the relationship between the ability of these therapies to reduce smoking behavior and promote abstinence and suicidality risks as assessed by reported suicidality on validated measures, reports of suicidal ideation, behaviors, actual attempts, or completed suicides. Pharmacotherapies such as varenicline, bupropion, and nicotine replacement, and CBTs, including contextual CBT interventions, have been found to help reduce smoking rates and promote and maintain abstinence. Suicidality risks, while present when trying to quit smoking, do not appear to demonstrate a consistent or significant rise associated with use of any particular smoking cessation pharmacotherapy or CBT/contextual CBT intervention reviewed.

Attitudes towards potentially carrying the FMR1 premutation: before vs after testing of non-carrier females with diminished ovarian reserve.

Diminished ovarian reserve (DOR) and premature ovarian failure are associated with elevated FMR1 CGG repeat alleles. We assessed pretest attitudes about potentially carrying the FMR1 premutation (FXP) (>55 CGG repeats) among reproductive age women compared with attitudes after learning their non-carrier status. Ninety-two women with DOR, regular menses and no family history of Fragile X Syndrome underwent FMR1 testing and completed attitudinal questionnaires before (T1) and 3 months after learning the test results (T2). The analysis utilized signed rank tests and α = 0.05. Very few women thought they were likely to have a FXP (6.6%). More participants thought FMR1 premutations were "serious" at T2 (62.9%) than at T1 (46.1%, p < 0.0003). When asked at T1 to "describe your feelings when you consider that you are potentially a carrier" of a FXP, 10% had negative feelings, 50% felt ambivalent, and 40% had positive feelings. At T2, feelings about not being a carrier were significantly more favorable (p < 0.0001): negative (0%), ambivalent (6.5%), positive (93%). Corroborating prior reports, few women had a negative view of FXP, perhaps anticipating that carrying the FXP explains their infertility. Perception of the seriousness of FXP increased after learning they did not carry the FXP, which would be predicted by health belief models.

Nonparaphilic hypersexual behavior and depressive symptoms: a meta-analytic review of the literature.

Research on nonparaphilic hypersexual behavior and its associated characteristics has increased in recent years. In the present article, the authors review the literature on the relation between nonparaphilic hypersexual behavior and depressive symptoms. There was a moderate, positive relation between nonparaphilic hypersexual behavior and depressive symptoms (r =.34). This relation was similar across gender, sexual orientation, and age. The authors discuss the implications for researchers and clinicians working with hypersexual individuals. Future research should work to elucidate the causal direction of the relation between nonparaphilic hypersexual behavior and depressive symptoms. The authors encourage clinicians who work with hypersexual patients to assess them for depressive symptoms and consider treatment options that address concurrent depressive symptoms.

Methodological review of treatments for nonparaphilic hypersexual behavior.

Research on nonparaphilic hypersexual behavior has increased in recent years. In the present article, the authors conducted a methodological review of empirical studies that evaluated a treatment for nonparaphilic hypersexual behavior. The authors reviewed several characteristics of the extant studies, including the participants, research designs, treatments evaluated, assessment of nonparaphilic hypersexual behavior, and outcomes. Despite several attempts to explore treatments aimed at attenuating the symptoms of nonparaphilic hypersexual behavior, the findings from this review indicate that much of the outcome research in the field contains significant methodological limitations. The authors conclude by offering recommendations to enhance future outcome research among investigators working with hypersexual populations.

Topiramate for the treatment of cocaine addiction: a randomized clinical trial.

IMPORTANCE: No medication has been established as an efficacious treatment for cocaine dependence. We hypothesized that dual modulation of the mesocorticolimbic dopamine system by topiramate-a glutamate receptor antagonist and γ-aminobutyric acid receptor agonist-would result in efficacious treatment for cocaine dependence compared with placebo. OBJECTIVE: To determine the efficacy of topiramate vs placebo as a treatment for cocaine dependence. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled, 12-week trial of 142 cocaine-dependent adults in clinical research facilities at the University of Virginia between November 22, 2005, and July 25, 2011. INTERVENTIONS: Topiramate (n = 71) or placebo (n = 71) in escalating doses from 50 mg/d to the target maintenance dose of 300 mg/d in weeks 6 to 12, combined with weekly cognitive-behavioral treatment. MAIN OUTCOMES AND MEASURES: For the efficacy period, weeks 6 to 12, the primary outcome was the weekly difference from baseline in the proportion of cocaine nonuse days; the secondary outcome was urinary cocaine-free weeks, and exploratory outcomes included craving and self- and observer-rated global functioning on the Clinical Global Impression scales. RESULTS: Using an intent-to-treat analysis, topiramate was more efficacious than placebo at increasing the weekly proportion of cocaine nonuse days, irrespective of whether missing data were not or were imputed conservatively to the baseline value (13.3% vs 5.3%, 95% CI for the estimated mean difference, 1.4%-14.6%, P = .02 or 8.9% vs 3.7%, 95% CI for the estimated mean difference, 0.2%-10.1%, P = .04, respectively). Topiramate also was associated, significantly more than placebo, with increasing the likelihood of urinary cocaine-free weeks (16.6% vs 5.8%; odds ratio, 3.21; 95% CI, 1.24-8.32; P = .02), as well as decreasing craving and improving observer-rated global functioning (all P < .05). CONCLUSIONS AND RELEVANCE: Topiramate is more efficacious than placebo at increasing the mean weekly proportion of cocaine nonuse days and associated measures of clinical improvement among cocaine-dependent individuals.

Depressive symptoms moderate treatment response to brief intervention for prevention of alcohol exposed pregnancy.

The previously published randomized controlled trial, EARLY, tested the efficacy of a motivational interviewing (MI) plus feedback condition against a video information (VI) condition and an informational brochure (IB) condition in reducing drinking and/or increasing contraception effectiveness, and found that drinking and rates of effective contraception improved in all conditions. In this reanalysis of the data from EARLY, potential moderating effects of depressive, global distress, and anxiety symptoms in response to the three brief interventions to reduce alcohol exposed pregnancy risk were examined. Women with higher levels of depression at baseline reported greater improvements in the MI plus feedback condition versus the VI and IB conditions with depression moderating both drinking and contraceptive effectiveness. Global distress moderated only drinking behavior in the MI plus feedback but not other groups and anxiety was not a moderator of outcome in any of the intervention groups. Depressed or distressed women at risk for AEP may benefit from an AEP risk reduction intervention that incorporates interaction with a treatment provider versus educational information provided via video or written materials.

Preconceptional motivational interviewing interventions to reduce alcohol-exposed pregnancy risk.

Alcohol exposed pregnancy (AEP) is a leading cause of preventable birth defects. While randomized controlled trials (RCTs) have shown that multi-session motivational interviewing-based interventions reduce AEP risk, a one-session intervention could facilitate broader implementation. The purposes of this study were to: (1) test a one-session motivational AEP prevention intervention for community women and (2) compare outcomes to previous RCTs. Participants at risk for AEP (N=217) were randomized to motivational interviewing+assessment feedback (EARLY), informational video, or informational brochure conditions. Outcomes were drinks per drinking day (DDD), ineffective contraception rate, and AEP risk at 3 and 6 months. All interventions were associated with decreased DDD, ineffective contraception rate, and AEP risk. Participants who received EARLY had larger absolute risk reductions in ineffective contraception and AEP risk, but not DDD. Effect sizes were compared to previous RCTs. The one-session EARLY intervention had less powerful effects than multi-session AEP prevention interventions among community women, but may provide a new option in a continuum of preventive care.

Changes in Affect and Drinking Outcomes in a Pharmacobehavioral Trial for Alcohol Dependence.

OBJECTIVE: Despite extensive research exploring affect in alcohol dependent individuals in recovery, empirical research on affective changes over the course of psychosocial treatment and their role on drinking outcomes has been minimal. The present study examined the relationship between changes in positive affect (PA), negative affect (NA), and drinking outcomes during a pharmacobehavioral trial. METHOD: Data for these post-hoc exploratory analyses were derived from a clinical trial of 321 alcohol dependent male and female individuals. The study design had four treatment arms for medication: three levels of dose of ondansetron as well as a control condition (placebo). All participants received weekly cognitive behavioral therapy for twelve weeks. We conducted an exploratory evaluation of changes in negative and positive affect and drinking behavior over time during the treatment phase of the trial using multilevel modeling. RESULTS: Participants experienced substantial reductions in drinking, decreases in NA, and increases in PA over the course of treatment. Individuals who experienced increases in PA over the course of treatment significantly reduced their drinking in subsequent weeks, while those who had reductions in NA only experienced reductions in drinking later in treatment if they also reported increases in PA. These results support the role of affect regulation in treatment. CONCLUSIONS: These results suggest that affective change during the course of treatment may serve as one potential mechanism of action for changes in drinking behavior. The interaction between reductions in NA and increases in PA may be particularly important in promoting new coping skills and reducing drinking.

Pharmacogenetic approach at the serotonin transporter gene as a method of reducing the severity of alcohol drinking.

OBJECTIVE: Severe drinking can cause serious morbidity and death. Because the serotonin transporter (5-HTT) is an important regulator of neuronal 5-HT function, allelic differences at that gene may modulate the severity of alcohol consumption and predict therapeutic response to the 5-HT(3) receptor antagonist, ondansetron. METHOD: The authors randomized 283 alcoholics by genotype in the 5'-regulatory region of the 5-HTT gene (LL/LS/SS), with additional genotyping for another functional single-nucleotide polymorphism (T/G), rs1042173, in the 3'-untranslated region, in a double-blind controlled trial. Participants received either ondansetron (4 µg/kg twice daily) or placebo for 11 weeks, plus standardized cognitive-behavioral therapy. RESULTS: Individuals with the LL genotype who received ondansetron had a lower mean number of drinks per drinking day (-1.62) and a higher percentage of days abstinent (11.27%) than those who received placebo. Among ondansetron recipients, the number of drinks per drinking day was lower (-1.53) and the percentage of days abstinent higher (9.73%) in LL compared with LS/SS individuals. LL individuals in the ondansetron group also had a lower number of drinks per drinking day (-1.45) and a higher percentage of days abstinent (9.65%) than all other genotype and treatment groups combined. For both number of drinks per drinking day and percentage of days abstinent, 5'-HTTLPR and rs1042173 variants interacted significantly. LL/TT individuals in the ondansetron group had a lower number of drinks per drinking day (-2.63) and a higher percentage of days abstinent (16.99%) than all other genotype and treatment groups combined. CONCLUSIONS: The authors propose a new pharmacogenetic approach using ondansetron to treat severe drinking and improve abstinence in alcoholics.

Measuring sexual addiction and compulsivity: a critical review of instruments.

Research has proliferated on sexual addiction in recent years, and this has led to an increase in the instruments created to measure this construct. The authors review 17 instruments that have been created to assess sexual addiction, including self-report rating scales, self-report checklists, and clinician rating scales measuring symptoms of sexual addiction, as well as self-report rating scales measuring consequences associated with sexual addiction. For each instrument, the authors describe its structure, conceptual basis, and samples studied. They also evaluate the evidence for the reliability and validity of each instrument. The instruments vary widely in their psychometric properties. Many have been created recently, and others have only been studied in specific populations. For each group of instruments, the authors make recommendations for researchers and clinicians.

Toward prevention of alcohol exposed pregnancies: characteristics that relate to ineffective contraception and risky drinking.

Alcohol-exposed pregnancy is a leading cause of preventable birth defects in the United States. This paper describes the motivational patterns that relate to risky drinking and ineffective contraception, two behaviors that can result in alcohol-exposed pregnancy. As part of an intervention study aimed at reducing alcohol-exposed pregnancy 124 women were recruited and reported demographic characteristics, readiness to change, stages of change, drinking, contraception, and sexual behavior history. Our results showed the following. Drinking: A significant positive correlation was found between the number of drinks consumed in 90 days and the Importance to reduce drinking (r = .23, p = .008). A significant negative correlation between number of drinks and confidence to reduce drinking (r = -.39, p = .000) was found as well. Significant differences were found in the total number of drinks consumed in 90 days between the five stages of change (F = (4,118), 3.12, p = .01). Women in Preparation reported drinking a significantly higher number of drinks than women in other stages of change. Contraception: There were significant negative correlations between ineffective contraception and Importance (r = -.38, p = .00), confidence (r = -.20, p = .02) and Readiness (r = -.43, p = .00) to use contraception effectively. Significant differences in contraception ineffectiveness were found for women in different stages of change (F = (4,115) 8.58, p = .000). Women in Precontemplation reported significantly higher levels of contraception ineffectiveness compared to women in other stages of change. Results show a clear relationship between higher alcohol consumption and higher levels of motivation to reduce drinking. In contrast, higher levels of ineffective contraception were related to lower levels of motivation to use contraception effectively. This suggests risky drinking may be better targeted with brief skills building interventions and ineffective contraception may require interventions that enhance problem awareness and motivation.

Evaluating readiness and treatment seeking effects in a pharmacotherapy trial for alcohol dependence.

BACKGROUND: Decreases in drinking behavior prior to treatment onset often occur in pharmacotherapy trials for alcohol dependence. We propose that these decreases are associated with both trait and state factors operating before initiation of treatment to influence participants' expectation or perception of future treatment outcome. While trait factors typically include personality traits, state factors can include readiness to change and severity of drinking at screening. Understanding the characteristics of changes in drinking early in the process of entering treatment can improve clinical trials and outcomes. Our goal was to evaluate drinking behavior before initiating a randomized, double-blind pharmacotherapy clinical trial for alcohol dependence. METHODS: We examined the impact of personality factors associated with gregariousness or conformity on the MacAndrew Alcoholism Scale, as well as state factors measured by the Stages-of-Change Scale (based on the University of Rhode Island Change Assessment Scale) and quantity of drinking at screening, on pre-double-blind clinical outcome (i.e., drinking reduction) among 321 male and female alcoholics enrolled in a pharmacotherapy trial. RESULTS: A significant reduction in alcohol consumption occurred among heavy drinkers between the baseline assessment (10.3 +/- 5.9 drinks per day) and the last week of single-blind placebo administration (5.3 +/- 5.1 drinks per day; p < 0.001). In contrast, the reduction in alcohol consumption by nonheavy drinkers over the same period was not significant (from 3.07 +/- 0.65 to 2.98 +/- 2.6 drinks per day; p > 0.05). Partial correlations indicated that the significant predictors of drinking reductions during this period were: level of drinking (-0.215) and the Stages-of-Change subscales of precontemplation (-0.152), contemplation (0.144), and maintenance (-0.284). Personality factors on the MacAndrew Alcoholism Scale did not predict drinking reductions during this same period. CONCLUSIONS: Participants with higher motivation levels and greater drinking severity were most likely to reduce their drinking behavior before double-blind treatment. These state factors are important to consider when randomizing participants in trials, and are more important than trait or personality factors in accounting for the initial reduction in drinking in this population during the pretreatment period.