BACKGROUND: Studies of the genetic basis of drug response could help clarify mechanisms of drug action/metabolism, and facilitate development of genotype-based predictive tests of efficacy or toxicity (pharmacogenetics). OBJECTIVES: We conducted a systematic review and field synopsis of pharmacogenetic studies to quantify the scope and quality of available evidence in this field in order to inform future research. DATA SOURCES: Original research articles were identified in Medline, reference lists from 24 meta-analyses/systematic reviews/review articles and U.S. Food and Drug Administration website of approved pharmacogenetic tests. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTION CRITERIA: We included any study in which either intended or adverse response to drug therapy was examined in relation to genetic variation in the germline or cancer cells in humans. STUDY APPRAISAL AND SYNTHESIS METHODS: Study characteristics and data reported in abstracts were recorded. We further analysed full text from a random 10% subset of articles spanning the different subclasses of study. RESULTS: From 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive). A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25ratio1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40-222]) with no trend to an increase over time, generated a high proportion (74.5%) of nominally significant (p<0.05) reported associations suggesting the possibility of significance-chasing bias. Despite 136 examples of gene/drug interventions being the subject of >/=4 studies, only 31 meta-analyses were identified. The majority (69.4%) of end-points were continuous and likely surrogate rather than hard (binary) clinical end-points. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The high expectation but limited translation of pharmacogenetic research thus far may be explained by the preponderance of reviews over primary research, small sample sizes, a mainly candidate gene approach, surrogate markers, an excess of nominally positive to truly positive associations and paucity of meta-analyses. Recommendations based on these findings should inform future study design to help realise the goal of personalised medicines. SYSTEMATIC REVIEW REGISTRATION NUMBER: Not Registered.

Objectives: Explore the relationship of self-esteem level, self-esteem stability, and admission functional status on discharge depressive symptoms in acute stroke rehabilitation. Research Method: One hundred twenty stroke survivors serially completed a measure of state self-esteem during inpatient rehabilitation and completed a measure of depressive symptoms at discharge. Functional status was rated at admission using the Functional Independence Measure (FIM). Regressions explored main effects and interactions of self-esteem level and stability and admission FIM self-care, mobility, and cognitive functioning on discharge depressive symptoms. Results: After controlling for potential moderating variables, self-esteem level interacted with FIM self-care and cognitive functioning to predict discharge depressive symptoms, such that survivors with lower self-rated self-esteem and poorer functional status indicated higher levels of depressive symptoms. Self-esteem stability interacted with FIM mobility functioning, such that self-esteem instability in the presence of lower mobility functioning at admission was related to higher depressive symptoms at discharge. Implications: These results suggest that self-esteem variables may moderate the relationship between functional status and depressive symptoms. Self-esteem level and stability may differentially moderate functional domains, although this conclusion requires further empirical support.(PsycINFO Database Record (c) 2009 APA, all rights reserved).

Objective: To explore self-esteem change during inpatient stroke rehabilitation and moderators of change. Research Method: One hundred twenty survivors of stroke serially completed the State Self-Esteem Scale (SSES) during inpatient rehabilitation, as well as measures of mood and perceived recovery as potential moderators of change. Age, gender, prior stroke, prestroke depression, stroke laterality, and admission Functional Independence Measure (FIM) self-care, mobility, and cognitive scores were also included as moderators. Results: Multilevel modeling of the repeated administrations of the SSES indicated that self-esteem significantly improved during rehabilitation. Female gender, left hemisphere stroke, prior stroke, and lower admission FIM cognitive scores were associated with lower self-esteem ratings at admission, but only age and admission FIM self-care and mobility scores were associated with self-esteem change. Older individuals showed less self-esteem improvement than younger individuals, and higher self-care and mobility scores at admission were associated with greater self-esteem improvement. While mood change significantly covaried with self-esteem, the rate of mood change did not appear to influence rate of self-esteem change. Greater improvement in self-esteem over time was related to lower levels of perceived recovery, but this was likely because of the relationship between perceived recovery and self-esteem at rehabilitation admission. Implications: These results suggest that self-esteem improves during inpatient rehabilitation, and this change may be partially dependent on functional status. Implications for facilitating self-esteem change by the clinician are discussed, as well as future research directions.(PsycINFO Database Record (c) 2009 APA, all rights reserved).

Objectives: Explore the relationship of self-esteem level, self-esteem stability, and other moderating variables with depressive symptoms in acute stroke rehabilitation. Measures: One hundred twenty participants completed measures of state self-esteem, perceived recovery, hospitalization-based hassles, impairment-related distress, and tendency to overgeneralize negative self-connotations of bad events. Self-report of depressive symptoms was collected at admission and on discharge. Four regression analyses explored the relationship of self-esteem level and stability and each of 4 moderating variables (perceived recovery, hassles, impairment-related distress, and overgeneralization) with depressive symptoms at discharge. Results: Analyses indicated significant 3-way interactions in the 4 regression models. In general, individuals with unstable high self-esteem endorsed greater depressive symptoms under conditions of vulnerability (e.g., lower perceived recovery) than did individuals with stable high self-esteem. Under conditions of vulnerability, participants with stable low self-esteem indicated the highest levels of depressive symptoms. Implications: Self-esteem level and stability interact with psychological, environmental, and stroke-specific variables to predict depressive symptoms at discharge from stroke rehabilitation. This suggests the viability of self-esteem stability in exploring depressive symptoms in this setting and the complexity of emotional adjustment early after stroke.(PsycINFO Database Record (c) 2009 APA, all rights reserved).

Objective: To compare ratings of self-esteem and depressive mood in a sample of stroke survivors in an acute inpatient rehabilitation setting to those of a matched control group.Design: Stroke survivors (n = 80) were matched on age and education to a group of neurologically intact community-dwelling control participants. Between-group analysis compared mean ratings of self-esteem and depressive measures. Within-group correlational analyses explored the relationship between self-esteem and mood. Between-group comparison of the correlations between self-esteem and mood explored differences in the strength of association between these constructs. Regression analyses explored the relationship of self-esteem measures after controlling for depressive mood.Main measures: Visual Analogue Self-Esteem Scale, Rosenberg Self-Esteem Scale, Geriatric Depression Scale.Results: Stroke survivors rated significantly lower mean levels of self-esteem on the Visual Analogue Self-Esteem Scale (37 versus 41) and the Rosenberg Self-Esteem Scale (21 versus 24) than the control group. Stroke survivors also rated higher mean levels of depressive mood on the Geriatric Depression Scale (9 versus 6). Significantly higher correlations between self-esteem and mood ratings were noted in the stroke group than in the control group. Lower self-esteem ratings do not appear to be a byproduct of depressive mood.Conclusions: Self-esteem is negatively impacted by stroke and is strongly, but independently, associated with depressive mood. Clinicians may better facilitate the emotional adjustment of the survivor by considering this facet of psychological impact and intervening to address self-esteem.

Vickery CD, Sherer M, Nick TG, Nakase-Richardson R, Corrigan JD, Hammond F, Macciocchi S, Ripley DL, Sander A. Relationships among premorbid alcohol use, acute intoxication, and early functional status after traumatic brain injury. OBJECTIVE: To investigate the relationships among intoxication at time of injury, preinjury history of problem drinking, and early functional status in patients with traumatic brain injury (TBI). DESIGN: Prospective cohort study. SETTING: Acute inpatient TBI rehabilitation. PARTICIPANTS: Participants were 1748 persons with TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Blood alcohol levels (BALs) were obtained at admission to the emergency department, and a history of problem drinking was obtained through interview. Study outcomes, Disability Rating Scale (DRS), and FIM instrument scores were gathered at admission to inpatient rehabilitation. RESULTS: Multivariate regression analysis revealed that BAL and a history of binge drinking were predictive of DRS, but not FIM, scores. A higher BAL was associated with poorer functional status on the DRS. Paradoxically, a history of binge drinking was associated with more intact functional status on the DRS. CONCLUSIONS: The relationships among intoxication at time of injury, history of problem drinking, and early outcome after TBI were modest. Injury severity had a more significant association with TBI functional status.

OBJECTIVE:: A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer. AIMS:: This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT. METHODS:: Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using preagreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat. RESULTS:: Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls. CONCLUSIONS:: This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased.

OBJECTIVE: To describe the characteristics of a non-verbal measure of self-esteem in a sample of individuals in the acute phase following stroke. DESIGN: Acute-phase stroke survivors (n=156) were administered measures of self-esteem, depression, anxiety, general emotional distress and cognitive functioning during admission to an inpatient stroke rehabilitation unit. MAIN MEASURES: Visual Analogue Self-Esteem Scale (VASES), Geriatric Depression Scale, Adult Manifest Anxiety Scale, Visual Analog Mood Scales, measures of neuropsychological functioning. RESULTS: VASES performance was not related to demographic variables, cognitive functioning, visual acuity, prior stroke or severe visuoperceptual impairment/left visual neglect. The VASES was most related to emotional functioning, with lower self-esteem ratings associated with higher levels of depressive symptoms and general emotional distress. Individuals with right hemisphere stroke tended to endorse lower self-esteem ratings, while aphasic individuals may have misunderstood the intent of the task. CONCLUSIONS: The non-verbal VASES appears to be minimally impacted by potentially invalidating patient factors (e.g. visual acuity, left visual neglect), although its use with patients with severe communication deficits is cautioned. The VASES may prove useful in identifying acute stroke survivors most at risk for emotional dysfunction, and may be useful as a research tool in this population.