Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer.

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

Impulsivity and Treatment Outcomes in Individuals with Cocaine Use Disorder: Examining the Gap between Interest and Adherence.

Background: Impulsivity is implicated in the development and maintenance of Cocaine Use Disorder (CUD). Less work has examined impulsivity's role on interest in initiating treatment, treatment adherence, or treatment response. No pharmacotherapies are approved for CUD, so efforts to understand and bolster the effects of psychotherapy are important in guiding and refining treatment. The present study examined the impact of impulsivity on interest in treatment, treatment initiation, treatment adherence, and treatment outcomes in individuals with CUD. Methods: Following the completion of a larger study on impulsivity and CUD participants were offered 14 sessions of (12 weeks) Cognitive Behavioral Relapse Prevention (CBT-RP). Before starting treatment, participants completed seven self-report and four behavioral measures of impulsivity. Sixty-eight healthy adults (36% female) with CUD (aged 49.4 ± 7.9) expressed an interest in treatment. Results: Greater scores on several self-report measures of impulsivity, and fewer difficulties with delayed gratification were associated with increased interest in treatment in both males and females. 55 participants attended at least 1 treatment session, while 13 participants did attend a single session. Individuals who attended at least one treatment session scored lower on measures of lack of perseverance and procrastination. Still, measures of impulsivity did not reliably predict session attendance nor the frequency of cocaine-positive urine samples throughout treatment. Males attended nearly twice as many treatment sessions as females despite nonsignificant associations between impulsivity in males and the number of sessions attended. Conclusions: Greater impulsivity in individuals with CUD was associated with expressing an interest in treatment, but not treatment adherence or response.

Assessment of the relationship between a written measure of empathy and an independently rated interview of Motivational Interviewing.

Motivational Interviewing (MI) is an evidence-based practice shown to be effective when working with people in treatment for substance use disorders. However, MI is a complex treatment modality optimized by training with feedback. Feedback, assessment and monitoring of treatment fidelity require measurement, which is typically done using audiotaped sessions. The gold standard for such measurement of MI skill has been an audiotaped interview, scored by a rater with a detailed structured instrument such as the Motivational Interviewing Treatment Integrity 2.0 (MITI 2.0) Coding System (Moyers, et al., 2005). The Helpful Responses Questionnaire (HRQ) (Miller, Hedrick, & Orlofsky, 1991) is a pen-and-paper test of empathy (a foundational MI skill) that does not require an audiotaped session. A randomized trial of three different regimens for training counselors in MI (live supervision using Teleconferencing, Tape-based supervision and Workshop only) (Smith et al., 2012) offered the opportunity to evaluate the performance of the HRQ as a measure of MI ability, compared to the several MITI 2.0 global scores and subscales. Participants were counselors (N=97) working at community-based substance use treatment programs, whose MI proficiency was measured at four time points: baseline (before an initial 2-day MI workshop), post-workshop, 8weeks post-workshop (i.e., post-supervision), and 20weeks post-workshop with both MITI 2.0 and HRQ. HRQ total scores correlated significantly with the Reflection to Question Ratio from the MITI 2.0 at post-workshop (r=0.33), week 8 (r=0.34), and week 20 (r=0.38), and with the Spirit (r=0.32) and Empathy (r=0.32) global scores at week 20. Correlations of HRQ with other MITI 2.0 subscales and time points after workshop were small and not significant. As predicted, HRQ scores differed between training conditions (X2(2)=7.88, p=0.02), with counselors assigned to live supervision achieving better HRQ scores than those in Workshop only. In summary, HRQ is a modestly accurate measure, mainly of the Reflection to Question Ratio, considered a core marker of MI skill. It is sensitive to training effects and may help identify counselors needing more intensive supervision. Given its ease of administration and scoring, HRQ may be a useful marker of MI skill during training efforts.

Simulation study of the effects of excluding early deaths on risk factor-mortality analyses in the presence of confounding due to occult disease: the example of body mass index.

PURPOSE: Estimating the effects of continuous chronic disease risk factors on mortality is an area that generates confusion and controversy. The frequently observed U-shaped or J-shaped relationships between the risk factors and mortality are often in contrast with presumed monotone relationships. Therefore, some investigators suggest that subjects dying during the first k years of follow-up (where k is some positive number less than the total length of follow-up) be excluded from statistical analyses. The rationale for this approach is that subjects dying during the first k years of follow-up are likely to have some pre-existing occult disease that confounds the relationship between the risk factors and mortality. Excluding such subjects purportedly reduces bias due to this confounding. The purpose of this study was to test the effects of excluding subjects who die during the first k years of follow-up on the reduction of bias under a variety of situations. METHODS: Using body mass index (BMI; kg/m2) as an example, we conducted Monte Carlo simulations to investigate such effects. RESULTS: Results suggest that under the conditions investigated, the method of excluding early deaths does not reliably or substantially reduce bias due to confounding introduced by occult disease. CONCLUSION: Excluding subjects dying during the first k years of follow-up may not be a judicious strategy for handling confounding due to occult disease. Investigators are encouraged to develop alternative methods.

Ophthalmic manifestations of allergic fungal sinusitis.

PURPOSE: To highlight allergic fungal sinusitis as a cause of ophthalmic and sinus problems by identifying the profile of the patient with allergic fungal sinusitis and presenting a successful treatment approach. METHODS: Six consecutive cases of patients with ophthalmic manifestations of allergic fungal sinusitis were reviewed. Ophthalmic findings, sinus involvement, mycology, immune response, imaging studies, and treatment were examined. The characteristics of this patient group with ophthalmic manifestations of allergic fungal sinusitis were compared with those of the general group of patients with allergic fungal sinusitis. RESULTS: All six patients had proptosis. One had symptomatic diplopia and one had visual loss. Imaging studies, fungal characterization, and immune profiles were similar to the reported allergic fungal sinusitis population. After treatment there was no recurrence of ophthalmic or sinus symptoms at a mean follow-up of 34 months (range, 8 to 48 months). There were no complications of treatment. CONCLUSIONS: Initial diagnosis of allergic fungal sinusitis requires suspicion on the part of the ophthalmologist. Proptosis is the most common ophthalmic sign. Differentiation from invasive forms of fungal sinus disease is crucial, because systemic antifungal medication and extensive surgical tissue debridement are not required in allergic fungal sinusitis. Treatment consists of extirpation of the allergic mucin and fungus, sinus aeration, and systemic and topical corticosteroids.

Cognitive impairment among the dually-diagnosed: substance use history and depressive symptom correlates.

The present study examined the effects of substance use history and depressive symptomatology on the cognitive functioning of 149 male and 72 female dually diagnosed inpatients. Logistic regression models examined the effects of life-time alcohol and cocaine use, previous month's alcohol and cocaine use and depression on abstract reasoning as assessed by the Shipley Institute of Living Scale (SILS) and neuropsychological functioning as measured by the Screening Test for the Luria-Nebraska Neuropsychological Battery (ST-LNNB). Results indicated differential effects of substance use across the two cognitive outcome measures. Specifically, a significant relationship was demonstrated for previous month's alcohol use on Shipley classification. However, after adjusting for possible borderline cases, previous month's alcohol use dropped to non-significance and in its stead an association between Shipley classification and life-time use was demonstrated. No significant effects were demonstrated for cocaine use, recent alcohol use, depressive symptoms or any of the interaction terms. The Luria-Nebraska performance classifications were significantly associated with both educational level and life-time cocaine use. No significant relationships were obtained for previous month's cocaine use, the alcohol use variables, depressive symptoms, or any of the interactions terms. The degree of classification agreement between the two outcome measures was slightly better than chance (kappa = 0.24 for ST-LNNB and traditional or full scale SILS; kappa = 0.35 for ST-LNNB and modified SILS). These kappa coefficients suggest that the SILS and ST-LNNB assess partially independent dimensions of cognitive functioning. The findings are discussed in light of previous research and implications for clinical assessment and treatment are outlined.

Reliability and discriminant validity of the Type I/II and Type A/B alcoholic subtype classifications in untreated problem drinkers: a test of the Apollonian--Dionysian hypothesis.

The present study tested the hypothesis that there are two broad groups of problem drinkers: the Apollonian-Dionysian distinction. Apollonian drinkers are defined by a later onset of alcohol problems, a slower developmental course, and less problem severity. Dionysian drinkers are defined by more severe alcohol problems, an earlier onset, and worse prognosis. The discriminant validity and classification agreement of five operations of the Apollonian-Dionysian model were tested in a general population (n=8643) and community sample (n=664). A kappa-means cluster analysis supported the Apollonian-Dionysian distinction. Dionysian problem drinkers were more likely to be males, report greater alcohol consumption, more alcohol related antisocial behavior, have a current DSM-IV alcohol dependence diagnosis, and comorbid depression. Apollonian problem drinkers were more prevalent in the general population and reported less severe drinking problems. Classification agreement was stronger for subtype models that incorporate dimensions of alcohol use and/or the frequency of negative consequences. Babor's Type A-Type B model demonstrated the strongest reliability and consistency over time.

The alcohol use disorder and associated disabilities interview schedule (AUDADIS): reliability of alcohol and drug modules in a clinical sample.

The alcohol use disorder and associated disabilities interview schedule (AUDADIS), was designed for use in the general population, and was previously shown to have good reliability in a sample of household residents. However, measurement problems are different in clinical samples. Thus, a test-retest study was conducted of the AUDADIS in a clinical sample of 296 substance-using patients from substance- and psychiatrically-identified treatment settings. Reliability for current drug-specific AUDADIS dependence diagnoses was good to excellent for high-prevalence as well as low-prevalence drug categories. Reliability for abuse diagnoses was not as good, although this was due to the hierarchical nature of the abuse diagnosis itself, rather than its defining criteria. Demographic and other factors were investigated for their potential effects on the reliability of alcohol and cocaine diagnoses; low severity was the only consistent predictor of unreliability for both of these categories. Reliability of consumption variables was generally good, with a few notable exceptions. Results suggest that the AUDADIS can be used in research comparing treated to community samples of individuals with alcohol and drug diagnoses.

Substance Dependence Severity Scale (SDSS): reliability and validity of a clinician-administered interview for DSM-IV substance use disorders.

No existing diagnostic interview assesses severity of dependence based on DSM-IV criteria across a range of substances. The Substance Dependence Severity Scale (SDSS) was designed to serve this purpose, consisting of substance-specific scales of both severity and frequency of DSM-IV criteria. This study investigated the reliability and validity of the SDSS. The test-retest reliability of the SDSS in 175 (112 male and 63 female) treated substance users ranged from good to excellent for alcohol, cocaine, heroin and sedatives (interclass correlation coefficients (ICCs)=0.75-0.88 for severity, 0.67-0.85 for frequency). Results for cannabis were lower, ranging from fair to good (ICCs=0.50-0.62). Results for joint rating and internal consistency reliability were comparable to test-retest findings. In addition to indicators of concurrent validity, scale applications are presented and discussed.

Concurrent and predictive validity of the Substance Dependence Severity Scale (SDSS).

This study investigated the concurrent and predictive validity of the Substance Dependence Severity Scale (SDSS), a clinician-administered interview designed to assess the severity and frequency of DSM-IV dependence symptoms for a range of substances. A total of 172 (107 males and 66 females) treated substance users participated in the study. Of those, 89% (n=153) received at least one follow-up interview within 1-6 months of an initial assessment. For alcohol, cocaine and heroin, convergent and discriminant validity was supported by significant relationships between SDSS scores at baseline and other baseline measures of substance use consequences, such as the Addiction Severity Index (ASI), as well as significant relationships between SDSS change scores from baseline to follow-up and change scores of other measures of consequences. SDSS scores were significantly associated with time to first post treatment use of alcohol, cocaine and heroin, although the nature of the associations was complex. Scale applications and areas for further study are discussed.

Drinking to cope with negative affect and DSM-IV alcohol use disorders: a test of three alternative explanations.

OBJECTIVE: Previous studies of drinking motives have demonstrated greater levels of drinking to cope with negative affect among problem drinkers relative to nonproblem drinkers. These findings suggest that the use of alcohol to cope with negative affect may place individuals at greater risk for the development of alcohol problems. However, several alternative explanations exist, each with different intervention implications. This study evaluated three alternative explanations or models: risk-factor, generalizing, and epiphenomena. A cross-sectional design was used to compare levels of self-reported drinking to cope with negative affect between individuals who had current DSM-IV alcohol use disorders and those who did not. METHOD: Participants consisted of a sample of community residents (N = 777, 55% men). All participants completed an in-person structured psychiatric interview and a self-report questionnaire assessing alcohol use, drinking motives, depressive affect, and negative alcohol consequences. RESULTS: Linear regression models yielded significant differences in mean drinking to cope with negative affect scores between participants with a DSM-IV alcohol dependence diagnosis and participants with no diagnosis. These differences remained after controlling for depressive affect and frequency of negative alcohol consequences in three of the four adjusted comparisons. No significant differences in adjusted mean drinking to cope with negative affect scores were demonstrated between subjects with a DSM-IV alcohol abuse diagnosis and those with no diagnosis. CONCLUSIONS: The DSM-IV alcohol dependence and no-diagnosis comparisons were most consistent with the predictions of a risk-factor model. These results provide further evidence that drinking to cope with negative affect may have an etiological role in development of alcohol dependence.

At-risk drinkers in the household and short-term course of alcohol dependence.

OBJECTIVE: Little is known about the effects of contextual factors on the chronicity of alcohol dependence in the general population. Many adults in the United States live with others in a wide range of relationships. The drinking of household members was investigated as a potential risk factor for persistence of DSM-IV alcohol dependence in a prospective study of household residents. METHOD: At-risk drinking (five or more drinks on at least one occasion) in adult household members living with respondents was assessed at the time of the baseline interview for the index subjects in the study (N = 128; 56% men) who lived with other adults and who met DSM-IV criteria for current alcohol dependence. Index subjects' drinking and demographic variables were also measured at baseline. Approximately 1 year later, follow-up interviews determined the status of alcohol dependence in the 128 subjects. RESULTS: Alcohol dependence was significantly more likely to be persistent among subjects with at-risk drinking among household members. CONCLUSIONS: The presence of other adult heavy drinkers in a household increased the risk of persistence of alcohol dependence in this community sample. Considerably more remains to be learned about the relationship and its treatment implications.

A prospective evaluation of the relationship between reasons for drinking and DSM-IV alcohol-use disorders.

Previous research has demonstrated an association between self-reported reasons for drinking and alcohol consumption. The most consistent relationships have been demonstrated between alcohol consumption and drinking for positive affect enhancement and coping with negative affect. However, most of the results have been from cross-sectional research designs that have not controlled for diagnostic status. The present study was a prospective investigation of the relationship between reasons for drinking and the Diagnostic and Statistical Manual of Mental Disorders (4th ed.), diagnoses of alcohol abuse and dependence. Subjects consisted of 508 community residents (264 male and 244 female) who did not meet DSM-IV criteria for an alcohol-use disorder at a baseline interview, who completed a completely structured interview (AUDADIS) and a self-report assessment battery, and who were re-interviewed approximately 1 year later. Results indicated a significant relationship between baseline reasons for drinking and follow-up diagnostic classification. Drinking to reduce negative affect predicted having a DSM-IV alcohol dependence diagnosis at follow-up, but not a diagnosis of alcohol abuse. No significant association was demonstrated between the baseline motive of drinking for positive affect enhancement and a follow-up DSM-IV alcohol-use disorder.

Substance Dependence Severity Scale: reliability and validity for ICD-10 substance use disorders.

The Substance Dependence Severity Scale (SDSS) is a semistructured interview that assesses the severity of the DSM-IV diagnoses of dependence and abuse and the ICD-10 diagnoses of substance dependence and harmful use across a wide range of substances. Previous research has demonstrated that the SDSS' DSM-IV dependence scales are reliable and valid indicators of diagnostic severity. However, the ICD-10 scales have not been psychometrically tested. This study investigated the test-retest reliability, internal consistency, diagnostic concordance, and concurrent validity of the SDSS' ICD-10 dependence and harmful use scales in 180 (112 male and 68 female) treated substance users. Test-retest reliabilities for the ICD-10 dependence scales ranged from good to excellent for alcohol, cocaine, heroin, and cannabis. Test-retest reliabilities for the SDSS' ICD-10 harmful use scales were in the good range for alcohol, cocaine, and heroin and the poor to fair range for cannabis. Internal consistency, diagnostic concordance, and concurrent validity results were comparable to the test-retest findings. These results support the use of the SDSS for assessing the severity of the ICD-10 dependence and harmful use diagnoses.

Gender-related factors influencing perceptions of homosexuality.

There is a long history linking gender role conformity to perceived homosexuality. However, the lack of a systematic theoretical model hinders the elucidation of the interrelationships among gender stereotypes, conformity to gender stereotypes, and perceived homosexuality, as well as other factors which may mediate these relationships. The purpose of the present study was to propose such a model by combining theories of gender stereotype formation and maintenance with research investigating perceptions of homosexuality. Specifically, this study examined college students' perceptions of gender role characteristics in male and female adult target persons and these students' perceptions of the likelihood that the targets were homosexual. Path analysis demonstrated that the sex and occupation of the target person were significantly related to perceived masculinity, femininity, and homosexuality of the target person. Furthermore, individual differences in these relationships were observed, indicating that the sex and gender role characteristics of the participant influenced perceptions of the gender role attributes and homosexuality of the target person.

Dimensional characteristics of the SCL-90-R: evaluation of gender differences in dually diagnosed inpatients.

The dimensional characteristics of the SCL-90-R were assessed for both male and female dually diagnosed inpatients. Subjects included 402 males and 227 females who presented with concurrent psychiatric and substance use disorders at a private psychiatric hospital. Confirmatory factor analyses resulted in the rejection of four previous measurement models for both genders including the original nine symptom dimensions. Subsequent principal component analyses resulted in four- and seven-component solutions for males and females, respectively; the majority of item covariation was accounted for by the first component. These results are consistent with previous research that has suggested a primary global distress factor and are in contrast to studies that have demonstrated factorial invariance across gender.

Difficulties with questions on usual drinking and the measurement of alcohol consumption.

Questions about usual drinking play an important role in the construction of alcohol consumption measures. However, little is known about difficulties in answering these questions for respondents with variability in their drinking patterns. We investigated this in a community sample of 945 drinkers and in a clinical sample of 400 patients treated for alcohol and/or drug problems. Demographic variables were not consistently related to self-reported difficulty in answering, but a diagnosis of current DSM-IV alcohol dependence was significantly related in both samples. In modeling the relationship between alcohol consumption and DSM-IV alcohol dependence, the fit of the model to the data was significantly improved by the addition of a variable indicating respondents' difficulty answering the usual drinking questions. Using this information in the development of alcohol consumption questions may provide more precise estimates of the risk from alcohol consumption to outcomes such as alcohol dependence.

The right answer for the wrong question: consequences of type III error for public health research.

OBJECTIVES: This study examined the impact of assessing the causes of interindividual variation within a population when the research question of interest is about causes of differences between populations or time periods. This discrepancy between the research focus and the research question is referred to as a type III error, one that provides the right answer for the wrong question. METHODS: Homelessness, obesity, and infant mortality were used to illustrate different consequences of type III errors. These different consequences depend on the relationships between the causes of within- and between-group variation. CONCLUSIONS: The causes of inter-individual variation and the causes of variation between populations and time periods may be distinct. The problem of examining invariant causes deserves attention.

Why, why, why?: Reason-giving and rumination as predictors of response to activation- and insight-oriented treatment rationales.

This study examines the relationships among the reasons a person offers for depression, the tendency to ruminate in response to depression, and reactions to activation-oriented (AO) or insight-oriented (IO) treatment rationales. Adults from the community (N=51) completed self-report measures of reason-giving and rumination and rated the credibility of, and personal reactions to, AO and IO rationales presented in written and videotape formats. Participants who gave more reasons for depression also tended to ruminate more in response to depressed mood. Reason-giving and rumination predicted lower credibility ratings and more negative personal reactions to the AO rationale. Although no relationship was found between these variables and response to the IO rationale, specific reasons were associated with different reactions to the two rationales. We discuss the roles of reason-giving and rumination in predicting responses to psychotherapies for depression.

Facial skeletal growth after endoscopic sinus surgery in the piglet model.

This study examined the effects of varying degrees of endoscopic sinus surgery on the growing midface and snout in pigs. In this randomized, controlled experiment, thirty 40-60 pound pigs were placed in five experimental groups: (1) unilateral uncinectomy; (2) bilateral uncinectomy; (3) unilateral uncinectomy, anterior ethmoidectomy, maxillary antrostomy; (4) bilateral uncinectomy, anterior ethmoidectomy, maxillary antrostomy; (5) unoperated controls. Animals were killed after 3 months and growth was assessed, according to linear and spatial measurements of multiple craniofacial regions. Euclidean distance matrix analysis showed significant restrictive shape alterations in a linear fashion in groups 1-4 (p < .05). These alterations occurred in the surgical field of the snout, midsnout, and maxilla. Endoscopic sinus surgery causes significant restrictive effects in the growing porcine facial skeleton.