This study investigated the effect of bacteriophages (phages) e11/2 and e4/1c against Escherichia coli O157:H7 in an ex vivo rumen model and in cattle in vivo. In the ex vivo rumen model, samples were inoculated with either 103 or 106 CFU/ml inoculum of E. coli O157:H7 and challenged separately with each bacteriophage. In the presence of phage e11/2, the numbers of E. coli O157:H7 bacteria were significantly (P < 0.05) reduced to below the limit of detection within 1 h. Phage e4/1c significantly (P < 0.05) reduced E. coli O157:H7 numbers within 2 h of incubation, but the number of surviving E. coli O157:H7 bacteria then remained unchanged over a further 22-h incubation period. The ability of a phage cocktail of e11/2 and e4/1c to reduce the fecal shedding of E. coli O157:H7 in experimentally inoculated cattle was then investigated in two cattle trials. Cattle (yearlings, n = 20 for trial one; adult fistulated cattle, n = 2 for trial two) were orally inoculated with 1010 CFU of E. coli O157:H7. Animals (n = 10 for trial one; n = 1 for trial two) were dosed daily with a bacteriophage cocktail of 1011 PFU for 3 days postinoculation. E. coli O157:H7 and phage numbers in fecal and/or rumen samples were determined over 7 days postinoculation. E. coli O157:H7 numbers rapidly declined in all animals within 24 to 48 h; however, there was no significant difference (P > 0.05) between the numbers of E. coli O157:H7 bacteria shed by the phage-treated or control animals. Phages were recovered from the rumen but not from the feces of the adult fistulated animal in trial two but were recovered from the feces of the yearling animals in trial one. While the results from the rumen model suggest that phages are effective in the rumen, further research is required to improve the antimicrobial effectiveness of phages for the elimination of E. coli O157:H7 in vivo.
Reported here is a water soluble Rh(I)-based catalyst for performing parahydrogen induced polarization (PHIP). The [Rh(I)(norbornadiene)(THP)2]+[BF4]- catalyst utilizes the monodentate phosphine ligand tris(hydroxymethyl)phosphine (THP). The monodentate PHIP catalyst is less susceptible to oxygenation by air and THP ligand and is significantly less expensive than bidentate water-soluble PHIP ligands. In situ PHIP detection with this monodentate Rh(I) based catalyst in water yielded 12% 13C polarization for the parahydrogen addition product, 2-hydroxyethyl 1-13C-propionate-d2,3,3 (HEP), with a 13C T1 relaxation of 108 seconds at 0.0475 T. PHIP polarization yields were high, reflecting efficient hydrogenation even under conditions of high content of the oxidized phosphine form of the THP ligand.
Parahydrogen; NMR; PASADENA; hyperpolarization; 13C; PHIP; catalysis; molecular hydrogenation; tris(hydroxymethyl)phosphine; rhodium
There is a significant need for advanced understanding of treatment of co-occurring posttraumatic stress disorder (PTSD) and substance use disorders (SUD). Approximately half of individuals seeking SUD treatment meet criteria for current PTSD, and individuals with co-occurring PTSD-SUD tend to have poorer treatment outcomes compared with those without such comorbidity. However, there is not sufficient empirical evidence to determine a best course of treatment for these individuals. This paper provides a review of the literature relevant to the treatment of co-occurring PTSD-SUD. To date, treatment studies have focused primarily on non-exposure-based psychosocial treatments, exposure-based psychosocial treatments, and medication trials. The most promising outcome data thus far are for psychosocial treatments that incorporate an exposure therapy component; however, further research is needed, particularly as related to how best to implement these approaches in real-world treatment settings.
Posttraumatic stress disorder; PTSD; Substance use; Substance abuse; Substance dependence; Addiction; Alcohol; Alcoholism; Cocaine; Prolonged exposure; Comorbidity; Anxiety; Treatment; Selective serotonin reuptake inhibitors; SSRI; Cognitive behavioral therapy; CBT
The colonic epithelium is composed of a polarized monolayer sheathed by a layer of pericryptal myofibroblasts (PCMFs). We mimicked these cellular compartments in vitro to assess the effects of paracrine-acting PCMF-derived factors on tight junction (TJ) integrity, as measured by transepithelial electrical resistance (TER). Co-culture with 18Co PCMFs, or basolateral administration of 18Co conditioned medium (CM), significantly reduced TER of polarized Caco-2 cells. Amongst candidate paracrine factors, only keratinocyte growth factor (KGF) reduced Caco-2 TER; basolateral KGF treatment led to time- and concentration-dependent increases in claudin-2 levels. We also demonstrate amphiregulin (AREG), produced largely by Caco-2 cells, increased claudin-2 levels, leading to epidermal growth factor receptor-mediated TER reduction. We propose that colonic epithelial TJ integrity can be modulated by paracrine KGF and autocrine AREG through increased claudin-2 levels. KGF-regulated claudin-2 induction may have implications for inflammatory bowel disease, where both KGF and claudin-2 are upregulated.
Tight junction; pericryptal myofibroblasts; keratinocyte growth factor; amphiregulin; claudin-2
The usage of reovirus has reached phase II and III clinical trials in human cancers. However, this is the first study to report the oncolytic effects of reovirus in veterinary oncology, focusing on canine mast cell tumor (MCT), the most common cutaneous tumor in dogs. As human and canine cancers share many similarities, we hypothesized that the oncolytic effects of reovirus can be exploited in canine cancers. The objective of this study was to determine the oncolytic effects of reovirus in canine MCT in vitro, in vivo and ex vivo. We demonstrated that MCT cell lines were highly susceptible to reovirus as indicated by marked cell death, high production of progeny virus and virus replication. Reovirus induced apoptosis in the canine MCT cell lines with no correlation to their Ras activation status. In vivo studies were conducted using unilateral and bilateral subcutaneous MCT xenograft models with a single intratumoral reovirus treatment and apparent reduction of tumor mass was exhibited. Furthermore, cell death was induced by reovirus in primary canine MCT samples in vitro. However, canine and murine bone marrow-derived mast cells (BMCMC) were also susceptible to reovirus. The combination of these results supports the potential value of reovirus as a therapy in canine MCT but warrants further investigation on the determinants of reovirus susceptibility.
To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ≤1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset.
microsatellite; STR; SNP; imputation; parentage verification
Men's reactions to a partner's abortion are an understudied area. Few studies have examined abortion as it relates to posttraumatic stress disorder (PTSD) in males, and no studies have examined the use of an empirically supported behavioral treatment for PTSD in this population. The current case study examines Prolonged Exposure for the treatment of abortion-related PTSD in a 46-year old Caucasian male who also has alcohol dependence. The patient was involved in a residential substance abuse treatment program at the time of treatment. After receiving 12 sessions of Prolonged Exposure, the patient experienced a decrease in PTSD symptoms as measured by the Clinician Administered PTSD Rating Scale (87%) and Impact of Event Scale-Revised (85%). The results of this study suggest that the literature supporting Prolonged Exposure as a first-line treatment for PTSD can be expanded to include men needing treatment for abortion-related PTSD. Implications for treatment and research are discussed.
Metaplastic lineages in the oxyntic mucosa of the stomach are critical preneoplastic precursors of gastric cancer. Recent studies have demonstrated that Spasmolytic polypeptide-expressing metaplasia (SPEM) in the mouse oxyntic mucosa arises from transdifferentiation of mature gastric chief cells. Other investigations of intestinal progenitor cells have shown that cells demonstrating transcriptional activity for Lgr5 in the intestine, colon and gastric antrum function as adult stem cells. We have now investigated whether cells demonstrating Lgr5 transcriptional activity in the oxyntic mucosa of mice might be responsible for development of metaplasia.
Lgr5-EGFP-IRES-CreERT2/+;Rosa26R mice were utilized to examine the distribution of Lgr5 transcriptionally active cells in the normal oxyntic mucosa as well as after treatment with DMP-777 or L635 to induce acute SPEM. Lineage mapping was performed to determine if LGR5-expressing cells gave rise to SPEM.
Cells expressing transcriptional activity for Lgr5 in the oxyntic mucosa were present as scattered rare cells only along the lesser curvature of the stomach. These cells also stained for markers of chief cells (intrinsic factor and pepsinogen) but never showed any staining for proliferative markers (Ki-67). In Lgr5-EGFP-IRES-CreERT2/+;Rosa26R mice induced with tamoxifen, treatment with either DMP-777 or L-635 to induce acute oxyntic atrophy caused induction of SPEM, but no lineage mapping into SPEM from Lgr5-expressing cells was observed.
The results indicate that, while chief cells with Lgr5-transcriptional activity are present along the lesser curvature of the gastric oxyntic mucosa, they are not responsible for production of metaplasia.
SPEM; chief cell; Lgr5; TFF2; oxyntic atrophy
This work demonstrates an anisotropic increase in resistivity with decreasing width in single crystal tungsten (W) nanowires having a height of 21 nm. Nanowire-widths were in the range of 15–451 nm, with the anisotropy observed for widths below 50 nm. The longitudinal directions of the nanowires coincided with the <100>, <110> and <111> orientations of the body centered cubic phase of W. The resistivity increase was observed to be minimized for the <111>-oriented single crystal nanowires, exhibiting a factor of two lower increase in resistivity at a width of ~15 nm, relative to the thin film resistivity (i.e., an infinitely wide wire). The observed anisotropy is attributed to crystallographic anisotropy of the Fermi velocity and the resultant anisotropy of the electron mean free path in W, and underscores the critical role of crystallographic orientation in nanoscale metallic conduction.
Background and Purpose
When planning clinical trials, decisions regarding sample size are often based on educated guesses of parameters, that may in fact prove to be over- or underestimates. For example, after initiation of the SPS3 study, published data indicated that the recurrent stroke rates might be lower than initially planned for the study. Failure to account for this could result in an under-powered study. Thus, we performed a sample size re-estimation, and describe the experience herein.
We evaluated different scenarios based on a re-estimated overall event rate, including increasing the sample size and increasing the follow-up time, to determine their impact on both Type I error and the power to detect the initially planned treatment difference.
We found that by increasing the sample size from 2500 to 3000 and by following the patients for one year after the end of recruitment, we would maintain our planned Type I error rate, and increase the power to detect the prespecified clinically meaningful difference to between 67% and 87%, depending on the rate of recruitment.
We successfully implemented this unplanned design modification in the SPS3 study, in order to allow for sufficient power to detect the planned treatment differences.
Clinical Trials Registration Information
Clinical Trials Registration - http://clinicaltrials.gov/show/NCT00059306. Unique identifier: NCT00059306
sample size re-estimation; SPS3; randomized clinical trial
In this work, we establish a methodology for comparing the efficiencies of different hydrazide labels for detecting protein carbonyls. We have chosen acrolein- modified human serum albumin as a model. This system provides a convenient means of reproducibly generating carbonylated protein. Five hydrazide-based labels were tested. Three carry a biotin affinity tag and the others are simple fatty acid hydrazides. For the biotin-based labels, the yield of the labeling reaction varies considerably and the most commonly used label, biotin hydrazide, gives the lowest yield. The total MS/MS spectrum counts of modified peptides are similar for all of the biotin-based tags indicating that factors beyond the labeling efficiency are important in determining the effectiveness of the label. In addition, there is a large variation in the number of spectra obtained for specific, modified peptides depending on the nature of the labeling group. This variation implies that the relative dectability of a particular modification site is highly dependent on the tagging reagent, and more importantly, titration schemes aimed at identifying the most reactive site based on its threshold concentration will be biased by the choice of tagging reagent. The fatty acid hydrazides are somewhat more effective than the biotin-based hydrazides in generating identifiable MS/MS spectra, but offer no opportunity for enrichment. For the biotin-based tags, avidin affinity chromatography was used with the tryptic digests and each tag led to similar enrichment levels.
Acrolein; Oxidative Stress; Protein Carbonylation; Mass Spectrometry
The purpose of this article is to describe the process of educating families and children with type 1 diabetes on real time continuous glucose monitoring (RT-CGM) and to note the similarities and differences of training patients using continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI).
A total of 30 CSII participants and 27 MDI participants were educated using the Navigator RT-CGM in a clinical trial. Time spent with families for visits and calls was tracked and compared between patient groups. The Diabetes Research in Children Network (DirecNet) educators were surveyed to assess the most crucial, time intensive, and difficult educational concepts related to CGM.
Of the 27 MDI families, an average of 9.6 hours was spent on protocol-prescribed visits and calls (not measured in CSII) and 2 hours on participant-initiated contacts over 3 months. MDI families required an average of 5.4 more phone contacts over 3 months than CSII families. According to the DirecNet educators, lag time and calibrations were the most crucial teaching concepts for successful RT-CGM use. The most time was spent on teaching technical aspects, troubleshooting, and insulin dosing. The most unanticipated difficulties were skin problems including irritation and the sensor not adhering well.
Educators who teach RT-CGM should emphasize lag time and calibration techniques, technical device training, and sensor insertion. Follow-up focus should include insulin dosing adjustments and skin issues. The time and effort required to introduce RT-CGM provided an opportunity for the diabetes educators to reemphasize good diabetes care practices and promote self-awareness and autonomy to patients and families.
The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) has been firmly established. Although laboratory studies have examined self-reported craving in response to trauma and alcohol cues, no studies have reported on alcohol-related physiological responding in response to trauma cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol-related responding (e.g., salivation, craving) in individuals with PTSD and AD (n=40). Participants displayed reactivity to both trauma and alcohol cues when compared to neutral cues, including increased self-reported craving and distress, as well as, greater salivation. These findings suggest that through repeated pairings of trauma memories and alcohol consumption, salivation may become classically conditioned to trauma cues. Moreover, the fact that the trauma-alcohol cue combination elicited greater alcohol craving, salivary responding, distress, and arousal than either the trauma-neutral or neutral-alcohol cue combinations, suggests that effects of the trauma and alcohol cues were additive in nature. Evidence that AD individuals with PTSD report increased alcohol craving and display greater salivation in response to trauma memories, supplements prior research indicating that PTSD-related negative emotion and trauma-related alcohol craving may play an important role in the maintenance of AD.
Alcohol abuse; posttraumatic stress disorder; comorbidity; cue reactivity; emotion; imagery
The current study employs dominance analysis to assess the relative importance of three constructs—hostility, impulsiveness, and emotional dysregulation (difficulties managing one’s emotions when experiencing negative emotion or distress)—in explaining psychological, physical, and sexual intimate partner violence (IPV) perpetration by men seeking alcohol treatment. A sample of 121 predominantly White, heterosexual men (average age 33.28, range = 18 - 62) enrolled in residential substance abuse treatment completed measures of emotional dysregulation, hostility, and impulsiveness, which are three highly related constructs identified as risk factors for both substance use disorders and IPV. The constructs collectively accounted for 20-25% of the variance in each form of IPV. Because impulsiveness, hostility, and emotional dysregulation are highly correlated, dominance analysis was used to examine which factor most strongly predicted each form of IPV. Dominance analysis findings favored hostility as a predictor of physical IPV perpetration, and impulsiveness as a predictor of sexual and psychological IPV perpetration. Differential associations between the constructs and each form of IPV may be used to inform assessment and treatment planning of men who abuse alcohol. Better understanding, preventing, and treating male-to-female IPV will protect women from the far-reaching consequences of this violence.
intimate partner violence; hostility; impulsiveness; emotional regulation; alcohol abuse
To examine the prevalence of binge drinking in adolescence and its persistence into adulthood in an Australian cohort.
15-year prospective cohort study.
1943 adolescents were recruited from secondary schools at age 14–15 years.
Primary outcome measures
Levels of past-week ‘binge’ drinking (5+ standard drinks on a day, each 10 g alcohol) and ‘heavy binge’ drinking (20+ standard drinks on a day for males, 11+ for females) were assessed during six adolescent waves, and across three adult waves up to age 29 years.
Half of the males (52%) and a third of the females (34%) reported past-week adolescent binge drinking. 90% of male and 70% of female adolescent-onset binge drinkers continued to binge in young adulthood; 70% of males and 48% of females who were not adolescent-onset binge drinkers reported young adult binge drinking. Past-week heavy bingeing was less common in adolescence than adulthood. Overall, 35% of the sample (95% CI 33% to 38%) reported past-week binge drinking in adolescence and young adulthood and one-third (33%; 30% to 35%) first reported binge drinking in young adulthood; only 7% of the sample (6–8%) had binge drinking in adolescence but not young adulthood. ‘Heavy binge’ drinking occurred in adolescence and young adulthood for 9% (8% to 10%); 8% (7% to 10%) reported it in adolescence but no longer in young adulthood; and 24% (22% to 26%) began ‘heavy binge’ drinking in young adulthood. Among adolescent binge drinkers (n=821), young adult binge and heavy binge drinking were predicted by being male, adolescent antisocial behaviour and adverse consequences of drinking in adolescence.
Binge alcohol use is common and persistent among young Australians. Efforts to prevent the onset of binge drinking during adolescence may substantially reduce harmful patterns of alcohol use in young adulthood.
Public Health; Epidemiology
Equine encephalosis virus (EEV) distribution was thought to be limited to southern Africa until 2008 when we reported EEV in Israel. It was then assumed that the clinical presentation resembled the initial incursion in Israel. To investigate further we conducted a retrospective analysis of equine sera, which had been collected for diagnosis of other suspected diseases, via serum neutralisation test. The data demonstrated that EEV was circulating as early as 2001 with incidence ranging from 20–100% for time period 2001–2008. As the symptoms of EEV can be similar to other equine notifiable diseases this is a significant finding which highlights the need for vigilance and education to accurately diagnose new and emerging diseases.
Chronic tic disorders (TD) are consistently found to have high rates of comorbidity with obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). The purpose of this study is to compare the severity of TD only to TD with comorbid OCD or ADHD based on severity of tics, measures of psychopathology and additional comorbid diagnoses. Baseline data from 158 youth with a chronic TD who participated in two longitudinal studies were examined. Fifty-three percent (N = 85) of the youth also met criteria for a diagnosis of OCD, 38.6 % (n = 61) met criteria for ADHD and 24.1 % (N = 38) met criteria for both. Measures of interest addressed severity of tics, symptoms of anxiety, depression, ADHD, psychosocial stress, global functioning and the presence of comorbid diagnoses. Youth with comorbid TD and OCD were characterized by more severe tics, increased levels of depressive and anxious symptoms, heightened psychosocial stress and poorer global functioning. Youth with comorbid TD and ADHD did not differ from those with TD alone on measures of tic severity, but experienced greater psychosocial stress and poorer global functioning. Subjects with comorbid TD and OCD had more internalizing disorders than those without OCD, while those with comorbid ADHD were more likely to meet criteria for oppositional defiant disorder. TD with OCD is a more severe subtype of TD than TD without OCD. TD with ADHD is associated with higher psychosocial stress and more externalizing behaviors. Further research is needed into the underlying relationships between these closely associated conditions.
Tourette's disorder; OCD ADHD; Comorbidity
Live animal trade is considered a major mode of introduction of viruses from enzootic foci into disease-free areas. Due to societal and behavioural changes, some wild animal species may nowadays be considered as pet species. The species diversity of animals involved in international trade is thus increasing. This could benefit pathogens that have a broad host range such as arboviruses. The objective of this study was to analyze the risk posed by live animal imports for the introduction, in the European Union (EU), of four arboviruses that affect human and horses: Eastern and Western equine encephalomyelitis, Venezuelan equine encephalitis and Japanese encephalitis. Importation data for a five-years period (2005-2009, extracted from the EU TRACES database), environmental data (used as a proxy for the presence of vectors) and horses and human population density data (impacting the occurrence of clinical cases) were combined to derive spatially explicit risk indicators for virus introduction and for the potential consequences of such introductions. Results showed the existence of hotspots where the introduction risk was the highest in Belgium, in the Netherlands and in the north of Italy. This risk was higher for Eastern equine encephalomyelitis (EEE) than for the three other diseases. It was mainly attributed to exotic pet species such as rodents, reptiles or cage birds, imported in small-sized containments from a wide variety of geographic origins. The increasing species and origin diversity of these animals may have in the future a strong impact on the risk of introduction of arboviruses in the EU.
Activation of the epidermal growth factor receptor (EGFR) requires cell surface cleavage of EGFR ligands, uptake of soluble ligand by the receptor, and initiation of EGFR tyrosine kinase activity. We define these collective events as the EGFR axis. Transforming growth factor-α (TGF-α) and amphiregulin are two EGFR ligands that are delivered preferentially to the basolateral surface of polarized epithelial cells where the EGFR resides. TACE/ADAM-17 (tumor necrosis factor-α converting enzyme/a disintegrin and metalloprotease) has been implicated in ectodomain cleavage of TGF-α and amphiregulin.
Using a human polarizing colorectal cancer (CRC) cell line, HCA-7, and a tissue array of normal colonic mucosa and primary and metastatic CRC, we determined the intracellular localization of TACE and the effects of EGFR axis inhibition in CRC.
Herein, we show that TACE is localized to the basolateral plasma membrane of polarized HCA-7 cells. TACE is overexpressed in primary and metastatic CRC tumors compared with normal colonic mucosa; the intensity of its immunoreactivity is inversely correlated with that of TGF-α and amphiregulin. Pharmacologic blockade of HCA-7 cells with an EGFR monoclonal antibody, a selective EGFR tyrosine kinase inhibitor, and a selective TACE inhibitor results in concentration-dependent decreases in cell proliferation and active, phosphorylated mitogen-activated protein kinase. Combining suboptimal concentrations of these agents results in cooperative growth inhibition, increased apoptosis, and reduced mitogen-activated protein kinase pathway activation. Furthermore, an EGFR tyrosine kinase – resistant clone of HCA-7 cells is growth-inhibited by combined monoclonal antibody and TACE inhibition.
These results implicate TACE as a promising target of EGFR axis inhibition in CRC.
Cells communicate with neighboring cells and condition their local environment by secreting soluble factors into the extracellular space. These well-studied facets of cell biology are essential for the establishment and maintenance of physiological homeostasis. However, accumulating evidence has revealed that specific ligands, enzymes, and macromolecules are distributed into the extracellular space by virtue of their association with small vesicles, which are released by a variety of cell types. Although the biological significance of such vesicles was initially debated, purification and subsequent functional studies have shown that these extracellular vesicles are bioactive organelles carrying a wide range of protein and nucleic acid cargoes. In many cases these vesicles are laden with molecules that are involved in cell signaling, although other diverse functions are being revealed at a rapid pace. In this Perspective, we discuss recent developments in the understanding of the major pathways of extracellular vesicle biogenesis and how these vesicles contribute to the maintenance of physiological homeostasis.
Previous research with substance users has demonstrated, across a variety of psychiatric disorders, significant decreases in psychological symptoms during early substance abstinence. To build on this literature, the current study prospectively assessed trauma symptomatology over 28 days during acute and protracted cocaine and alcohol abstinence. Participants were 162 male and female cocaine and/or alcohol dependent outpatients who reported a history of trauma. Trauma-related symptoms and substance use were assessed at 2, 5, 10, 14, 21, and 28 days following last substance use. For participants who were known to relapse, assessments began again after the last day of substance use. Latent growth modeling was employed to estimate changes in posttraumatic stress disorder (PTSD) symptoms. Consistent with studies of other psychiatric syndromes, PTSD symptoms declined across the 28-day study period regardless of withdrawal substance (i.e., cocaine or alcohol). The majority of change in trauma symptoms occurred within two weeks of last substance use. Moreover, while trauma symptoms for the PTSD participants were more severe than those reported by the non-PTSD participants, trauma symptoms declined across the study period at the same rate irrespective of PTSD status.
PTSD; Trauma; Co-morbidity; Withdrawal; Alcoholism; Cocaine Dependence
Despite growing recognition of the importance of multidimensional assessments of craving, little is known about how both approach and avoidance of alcohol inclinations change during the course of treatment, or relate to treatment outcomes. The current study examined the relationship between approach inclinations, avoidance inclinations, and treatment outcomes in individuals seeking treatment for alcohol dependence, and investigated whether changes in approach and avoidance ratings were associated with changes in drinking.
Individuals (n=81) seeking treatment for alcohol dependence were randomized to receive either 12-sessions of cognitive-behavioral therapy plus healthy living skills or 12-sessions of cognitive-behavioral therapy plus affect regulation training. Participants provided pre- and post- treatment scores on various measures including drinking behaviors and approach and avoidance inclinations to use alcohol.
Results indicated that both approach and avoidance inclinations were uniquely and significantly associated with problem recognition, and that avoidance inclinations were uniquely related to taking steps to make a change in alcohol use at baseline. In addition, avoidance inclinations were positively associated with number of sessions attended with no association found for approach ratings. Finally, results suggested that changes observed in drinking outcomes (drinks/day and % days abstinent) were significantly associated with changes in approach, but not avoidance inclinations.
These findings highlight the importance of measuring both desire to consume and desire to avoid consuming alcohol simultaneously and suggest that avoidance inclinations are associated with treatment initiation and retention, and approach inclinations with positive treatment outcomes.
alcohol; treatment outcomes; craving; approach; avoidance
It is uncertain if computerized physician order entry (CPOE) systems are effective at reducing adverse drug event (ADE) rates in community hospitals, where mainly vendor-developed applications are used.
To evaluate the impact of vendor CPOE systems on the frequency of ADEs.
DESIGN AND PATIENTS
Prospective before-and-after study conducted from January 2005 to September 2010 at five Massachusetts community hospitals. Participants were adults admitted during the study period. A total of 2,000 charts were reviewed for orders, medication lists, laboratory reports, admission histories, notes, discharge summaries, and flow sheets.
The primary outcome measure was the rate of preventable ADEs. Rates of potential ADEs and overall ADEs were secondary outcomes.
The rate of preventable ADEs decreased following implementation (10.6/100 vs. 7.0/100 admissions; p = 0.007) with a similar effect observed at each site. However, the associated decrease in preventable ADEs was balanced against an increase in potential ADEs (44.4/100 vs. 57.5/100 admissions; p < 0.001). We observed a reduction of 34.0% for preventable ADEs, but an increase of 29.5% in potential ADEs following implementation. The overall rate of ADEs increased (14.6/100 vs. 18.7/100 admissions; p = 0.03), which was driven by non-preventable events (4.0/100 vs. 11.7/100 admissions; p < 0.001).
Adoption of vendor CPOE systems was associated with a decrease in the preventable ADE rate by a third, although the rates of potential ADEs and overall ADEs increased. Our findings support the use of vendor CPOE systems as a means to reduce drug-related injury and harm. The potential ADE rate could be reduced by making refinements to the vendor applications and their associated decision support.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-1987-7) contains supplementary material, which is available to authorized users.
medication safety; adverse drug events; unintended consequences