Prospective Risk Factor Analysis for the Development of Post-operative Urinary Retention Following Ambulatory General Surgery.

AIMS: Post-operative urinary retention (POUR) is a common cause of unplanned admission following day-case surgery and has negative effects on both patient and surgical institution. We aimed to prospectively evaluate potential risk factors for the development of POUR following day-case general surgical procedures. METHODS: Over a 24-week period, consecutive adult patients undergoing elective day-case general surgery at a single institution were prospectively recruited. Data regarding urinary symptoms, comorbidities, drug history, surgery and perioperative anaesthetic drug use were collected. The primary outcome was the incidence of POUR, defined as an impairment of bladder voiding requiring either urethral catheterisation, unplanned overnight admission or both. Potential risk factors for the development of POUR were analysed by logistic regression. RESULTS: A total of 458 patients met the inclusion criteria during the study period, and data were collected on 382 (83%) patients (74.3% male). Sixteen patients (4.2%) experienced POUR. Unadjusted analysis demonstrated three significant risk factors for the development of POUR: age ≥ 56 years (OR 7.77 [2.18-27.78], p = 0.002), laparoscopic surgery (OR 3.37 [1.03-12.10], p = 0.044) and glycopyrrolate administration (OR 5.56 [2.00-15.46], p = 0.001). Male sex and lower urinary tract symptoms were not significant factors. Multivariate analysis combining type of surgery, age and glycopyrrolate use revealed that only age ≥ 56 years (OR 8.14 [2.18-30.32], p = 0.0018) and glycopyrrolate administration (OR 3.48 [1.08-11.24], p = 0.0370) were independently associated with POUR. CONCLUSIONS: Patients aged at least 56 years and/or requiring glycopyrrolate-often administered during laparoscopic procedures-are at increased risk of POUR following ambulatory general surgery.

Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis.

BACKGROUND: Current management of suspected appendicitis is hampered by the overadmission of patients with non-specific abdominal pain and a significant negative exploration rate. The potential benefits of risk stratification by the Appendicitis Inflammatory Response (AIR) score to guide clinical decision-making were assessed. METHODS: During this 50-week prospective observational study at one institution, the AIR score was calculated for all patients admitted with suspected appendicitis. Appendicitis was diagnosed by histological examination, and patients were classified as having non-appendicitis pain if histological findings were negative or surgery was not performed. The diagnostic performance of the AIR score and the potential for risk stratification to reduce admissions, optimize imaging and prevent unnecessary explorations were quantified. RESULTS: A total of 464 patients were included, of whom 210 (63·3 per cent) with non-appendicitis pain were correctly classified as low risk. However, 13 low-risk patients had appendicitis. Low-risk patients accounted for 48·1 per cent of admissions (223 of 464), 57 per cent of negative explorations (48 of 84) and 50·7 per cent of imaging requests (149 of 294). An AIR score of 5 or more (intermediate and high risk) had high sensitivity for all severities of appendicitis (90 per cent) and also for advanced appendicitis (98 per cent). An AIR score of 9 or more (high risk) was very specific (97 per cent) for appendicitis, and the majority of patients with appendicitis in the high-risk group (21 of 30, 70 per cent) had perforation or gangrene. Ultrasound imaging could not exclude appendicitis in low-risk patients (negative likelihood ratio (LR) 1·0) but could rule-in the diagnosis in intermediate-risk patients (positive LR 10·2). CT could exclude appendicitis in low-risk patients (negative LR 0·0) and rule-in appendicitis in the intermediate group (positive LR 10·9). CONCLUSION: Risk stratification of patients with suspected appendicitis by the AIR score could guide decision-making to reduce admissions, optimize utility of diagnostic imaging and prevent negative explorations.

The use of Lean and Six Sigma methodologies in surgery: a systematic review.

BACKGROUND: Lean and Six Sigma are improvement methodologies developed in the manufacturing industry and have been applied to healthcare settings since the 1990 s. They use a systematic and reproducible approach to provide Quality Improvement (QI), with a flexible process that can be applied to a range of outcomes across different patient groups. This review assesses the literature with regard to the use and utility of Lean and Six Sigma methodologies in surgery. METHODS: MEDLINE, Embase, PsycINFO, Allied and Complementary Medicine Database, British Nursing Index, Cumulative Index to Nursing and Allied Health Literature, Health Business Elite and the Health Management Information Consortium were searched in January 2014. Experimental studies were included if they assessed the use of Lean or Six Sigma on the ability to improve specified outcomes in surgical patients. RESULTS: Of the 124 studies returned, 23 were suitable for inclusion with 11 assessing Lean, 6 Six Sigma and 6 Lean Six Sigma. The broad range of outcomes can be collated into six common aims: to optimise outpatient efficiency, to improve operating theatre efficiency, to decrease operative complications, to reduce ward-based harms, to reduce mortality and to limit unnecessary cost and length of stay. The majority of studies (88%) demonstrate improvement; however high levels of systematic bias and imprecision were evident. CONCLUSION: Lean and Six Sigma QI methodologies have the potential to produce clinically significant improvement for surgical patients. However there is a need to conduct high-quality studies with low risk of systematic bias in order to further understand their role.

Short communication: an in vitro assessment of the antibacterial activity of plant-derived oils.

Nonantibiotic treatments for mastitis are needed in organic dairy herds. Plant-derived oils may be useful but efficacy and potential mechanisms of action of such oils in mastitis therapy have not been well documented. The objective of the current study was to evaluate the antibacterial activity of the plant-derived oil components of Phyto-Mast (Bovinity Health LLC, Narvon, PA), an herbal intramammary product, against 3 mastitis-causing pathogens: Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis. Plant-derived oils evaluated were Thymus vulgaris (thyme), Gaultheria procumbens (wintergreen), Glycyrrhiza uralensis (Chinese licorice), Angelica sinensis, and Angelica dahurica. Broth dilution testing according to standard protocol was performed using ultrapasteurized whole milk instead of broth. Controls included milk only (negative control), milk + bacteria (positive control), and milk + bacteria + penicillin-streptomycin (antibiotic control, at 1 and 5% concentrations). Essential oil of thyme was tested by itself and not in combination with other oils because of its known antibacterial activity. The other plant-derived oils were tested alone and in combination for a total of 15 treatments, each replicated 3 times and tested at 0.5, 1, 2, and 4% to simulate concentrations potentially achievable in the milk within the pre-dry-off udder quarter. Thyme oil at concentrations ≥2% completely inhibited bacterial growth in all replications. Other plant-derived oils tested alone or in various combinations were not consistently antibacterial and did not show typical dose-response effects. Only thyme essential oil had consistent antibacterial activity against the 3 mastitis-causing organisms tested in vitro. Further evaluation of physiological effects of thyme oil in various preparations on mammary tissue is recommended to determine potential suitability for mastitis therapy.

Milk and plasma disposition of thymol following intramammary administration of a phytoceutical mastitis treatment.

Despite the recent growth of the organic dairy industry, organic producers and veterinarians have limited information when choosing mastitis treatments for animals in organic dairy production. Organic producers commonly administer homeopathic or other plant-based products without having research evaluating the efficacy of these products and using estimated or no withholding times to treat mastitis and other health problems in their herds. In this pilot study, we attempted to identify several active ingredients of Phyto-Mast (Penn Dutch Cow Care, Narvon, PA), a plant-based mastitis treatment used on organic dairy farms, and to quantify the product residue in milk and plasma after intramammary administration. We developed an assay to quantify thymol (one of the active ingredients in Phyto-Mast) in milk and plasma using gas chromatography and mass spectrometry (GC-MS). Thymol is a volatile aromatic compound with antiinflammatory properties. As a model for dairy cows, 5 healthy, lactating alpine dairy goats were given 5 mL of Phyto-Mast per udder half. For 10 d following treatment, we analyzed blood and milk samples for thymol residues using GC-MS. The GC-MS assay was very sensitive for thymol detection, to a concentration of 0.01 µg/mL in plasma. Using thymol as a marker, Phyto-Mast was detectable and quantifiable in plasma beginning with the 15-min posttreatment sample, but was no longer detectable in the 4-h posttreatment sample. Thymol residues were only detected in the 12-h posttreatment milk sample. An inflammatory response was not evident in the udder following phytoceutical administration. Although this study provides information about the elimination of thymol, the product contains several other active chemicals, which may have different pharmacokinetic behaviors. Further analysis and additional study animals will help to determine a milk withholding time for Phyto-Mast. Given the recent growth of the organic dairy industry, understanding the pharmacokinetics of therapeutics used in organic production and developing accurate withholding recommendations will help to ensure milk safety.

Maintenance imipramine therapy for secondary depression in schizophrenia. A controlled trial.

BACKGROUND: Although recent studies have documented the benefit of adjunctive antidepressant medication for the short-term treatment of certain patients with operationally defined syndromes of postpsychotic depression, the value of maintenance adjunctive antidepressant treatment in this circumstance has not been properly established. METHODS: This study examined 24 schizophrenic or schizoaffective patients with postpsychotic depression or negative symptoms. These patients had all been benefited over the short term by the addition of adjunctive imipramine hydrochloride to their ongoing fluphenazine decanoate/benztropine mesylate regimens, and this adjunctive treatment had been successfully continued for 6 months. In a randomized double-blind protocol, treatment with adjunctive imipramine hydrochloride (mean, 233 +/- 72 mg/d) was then either maintained or tapered to placebo for an ensuing 1-year trial, while treatment with fluphenazine and benztropine continued. RESULTS: Significantly more patients who received placebo substitution relapsed into depression (P < .001). Patients who received placebo substitution were also more likely to experience relapses into psychosis (P < .02). CONCLUSIONS: These results support the clinical value of maintenance adjunctive imipramine therapy among initially responsive patients with postpsychotic depressions.

Isolation and characterization of the [Ga2Al18O8(OH)36(H2O)12](8+) cluster: cationic variations on the Wells-Dawson topology.

The structural chemistry of Group 13 polyoxometalates lags far behind related negatively charged transition metal species and limits the development of advanced materials. A novel heterometallic cluster [Ga2Al18O8(OH)36(H2O)12](8+) (Ga2Al18) has been isolated using a supramolecular approach and structurally characterized using single-crystal X-ray diffraction. Ga2Al18 represents the Wells-Dawson structure polycations and variations in the structural topology may be related to the initial stabilization of the Keggin isomer. DFT calculations on the related ε-Keggins (GaAl12 and Al13), Ga2Al18, and theoretical Al2Al18 clusters reveal similar features of electronic structure, suggesting additional heteroatom substitution in other isostructural clusters should be possible.

Correlations between immediate early gene induction and the persistence of long-term potentiation.

The duration of long-term potentiation in the dentate gyrus of awake rats was examined following systematic manipulation of the number of stimulus trains delivered. This was correlated with the induction of immediate early genes in separate groups of animals given identical stimulus regimes. Following 10 trains of stimulation, long-term potentiation decayed with a time constant of up to several days (long-term potentiation 2), and this correlated with the appearance of an increase in the messenger RNA and protein levels of zif/268. Increasing the number of stimulus trains resulted in a greater probability of eliciting long-term potentiation with a time constant of several weeks (long-term potentiation 3), as well as increasing the induction of zif/268, c-Jun, Jun-B, Jun-D and Fos-related proteins. When 10 trains were delivered repeatedly on up to five consecutive days, only the zif/268 protein levels showed associated changes. These data provide support for the hypothesis that long-term potentiation 3 involves mechanisms additional to those for long-term potentiation 2. One possible mechanism is altered gene expression, initiated by immediate early gene transcription factors such as zif/268 and possibly homo- or heterodimers of Fos and Jun family members, that then contributes to the stabilization or maintenance of long-term potentiation 3.

Induction of Fos-like immunoreactivity and the maintenance of long-term potentiation in the dentate gyrus of unanesthetized rats.

Memory formation in the mammalian central nervous system may require long-lasting alterations in gene expression. However, it is not yet known whether the candidate memory mechanism long-term potentiation (LTP) requires alterations in gene expression for its maintenance, nor the extent to which the time course of LTP can be manipulated at the time of induction. In this study we influenced the time course of LTP decay for the perforant path input to the dentate gyrus in awake rats by manipulating conditions at the time of induction, and correlated the outcome with the induction of c-fos protein(s) (Fos), as measured immunohistochemically in the dentate gyrus of separate animals 2 h post-tetanization. Sodium pentobarbital, which blocks the induction of Fos-like immunoreactivity (Fos-IR), also blocked a long-duration form of LTP maintained over weeks. On the other hand, two different patterns of delivery of 50 trains, that produced similar time courses of LTP decay, produced markedly different degrees of Fos-IR induction. In addition, while stimulation consisting of only 10 trains induced a sizable Fos response, it only produced LTP lasting a few days. When the 10-train stimulation was repeated on 3 or 5 consecutive days, there appeared to be no additional Fos-IR induction, yet the LTP decay time constant was considerably prolonged. Thus there is little correlation between the degree of Fos-IR induction and the subsequent durability of LTP.

Total lung capacity. An insensitive measure of impairment in patients with asbestosis and chronic obstructive pulmonary disease?

The total lung capacity (TLC) is frequently used as a measure of respiratory impairment in patients with asbestosis. Because asbestosis and chronic obstructive pulmonary disease (COPD) exert opposite effects on the TLC, it may be an insensitive measure of impairment in patients with both abnormalities. To assess this, we compared asbestos-exposed patients with functional evidence of COPD and radiographic evidence of interstitial fibrosis (group 1) to those with interstitial fibrosis alone (group 2). Despite the two groups being comparable in degree of radiographic "fibrosis," no case of restrictive impairment (reduced TLC) was identified among those with both interstitial fibrosis and COPD (group 1), compared to 33 percent of those with interstitial fibrosis alone (group 2). In addition, those patients with both interstitial fibrosis and COPD, compared to those with interstitial fibrosis alone, were found to have greater impairment as measured by alveolar-arterial oxygen difference and diffusing capacity. We conclude that the TLC is an insensitive measure of impairment due to asbestosis in patients with the common setting of coexistent asbestosis and COPD.

Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats.

The pattern of expression of fos and jun family immediate early genes following the induction of long-term potentiation (LTP) was investigated in the dentate gyrus of awake rats. Rapid, transient increases in the levels of c-jun and jun-B mRNA and protein, and in the levels of Fos-related proteins (FRAs), occurred in the dentate gyrus after LTP-inducing tetanization of the perforant path. A delayed, and more prolonged induction occurred for jun-D mRNA and protein. The induction of c-Jun, Jun-B, Jun-D and Fos-related proteins was prevented by administration of an N-methyl-D-aspartate receptor antagonist, which also blocked LTP induction, and by pentobarbital, which reduced but did not block LTP. These findings show that differential expression of fos and jun gene family members occurs in a distinct pattern following LTP in awake rats. The responsive genes may participate in the biochemical cascade leading to the long-term stabilization of synaptic modifications.

Effects of the NMDA receptor/channel antagonists CPP and MK801 on hippocampal field potentials and long-term potentiation in anesthetized rats.

The effects of the competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, 3-[(+/- )-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK801) were tested on hippocampal field potentials and long-term potentiation (LTP) in urethane-anesthetized rats. Neither drug had any significant effects on the dentate hilar population excitatory postsynaptic potential (EPSP) evoked by perforant path stimulation 30 or 150 min postinjection. However, both drugs produced a dose-dependent decrease in population spike amplitude at these times. Both drugs (at the highest doses) also blocked LTP when induced 150 min after administration, and this was related to a smaller response evoked during tetanization. CPP exerted similar effects on commissural-CA1 evoked responses and LTP. CPP remained an effective blocker of LTP for 6-8 h, and was still partially effective after 20-24 h. MK801 washed out more rapidly. The effect of MK801 on LTP did not depend on stimulus-evoked transmitter release during the pretetanization period. The results indicate that both CPP and MK801 have potent effects on LTP in the in vivo preparation, but that this is accompanied by an independent effect on evoked cell discharge.

Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols. zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence, zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.

Long-term potentiation and the induction of c-fos mRNA and proteins in the dentate gyrus of unanesthetized rats.

We tested the hypothesis that the nuclear proto-oncogene c-fos is involved in long-term potentiation (LTP) of the perforant path-dentate gyrus synapse in awake freely moving rats. High-frequency stimulation that produced LTP induced c-fos mRNA and protein in the dentate granule cells but not in CA1, CA3, or the entorhinal cortex. However, the degree of LTP induction did not correlate with the degree of c-fos induction. Agents that interfered with the production of LTP (e.g. NMDA antagonists) also prevented c-fos induction. Low-frequency stimulation did not lead to either LTP or c-fos induction. However, c-fos induction did not necessarily follow LTP production because some high-frequency stimulation protocols that produced good LTP did not lead to c-fos induction. Thus, c-fos induction is clearly not related to LTP production in unanaesthetized rats, but it remains to be determined if it plays some role in LTP maintenance.

Histories of substance abuse, panic and suicidal ideation in schizophrenic patients with histories of post-psychotic depressions.

1. Forty patients who had had syndromally-defined episodes of post-psychotic depression at least 6 months previously were interviewed in detail for life-time histories of substance abuse, panic attacks, and suicidal ideation. 2. No relationship was found between life-time history of suicidal ideation and substance abuse. 3. Statistically significant associations were found between lifetime history of suicidal ideation and both a life-time history of panic attacks and the panic disorder syndrome.

Adjunctive imipramine for dysphoric schizophrenic patients with past histories of cannabis abuse.

1. Twenty-one schizophrenic or schizoaffective patients with histories of cannabis abuse and operationally-defined syndromes of post-psychotic depression completed a double-blind trial of adjunctive imipramine added to their on-going medication regimen of fluphenazine decanoate and benztropine. 2. The imipramine-treated patients had superior global outcome. 3. Subscales suggested that specific improvement occurred in imipramine-treated patients in the domain of depression-like features. 4. Psychotic symptomatology was not found to be exacerbated by the imipramine.

Antidepressant for substance-abusing schizophrenic patients: a minireview.

1. Substance abuse and post-psychotic depression are both frequently encountered concomitants of schizophrenia. 2. Substance abuse may be associated with depression-like symptomatology in the course of schizophrenia, and patients may attempt to self-medicate these symptoms with substances of abuse. 3. Antidepressant medication has been found to be a useful adjunct to treatment in at least some cases of substance abuse and some cases of post-psychotic depression. 4. Preliminary evidence exists suggesting that adjunctive antidepressant medication, added to a neuroleptic, may be useful for at least some stable dysphoric substance-abusing schizophrenic patients. 5. It is important to attempt to rule out even subtle neuroleptic-induced akinesia in such patients with a vigorous trial of antiparkinsonian medication.

Effects of the NMDA antagonists CPP and MK-801 on radial arm maze performance in rats.

The dose- and time-dependent effects of N-methyl-D-aspartate receptor/channel antagonists on radial 8-arm maze performance were examined in rats. Both CPP (1.0-30 mg/kg), a competitive NMDA antagonist, and MK-801 (0.1-1.0 mg/kg), a noncompetitive NMDA antagonist, produced dose-dependent increases in the number of errors made to sample all 8 baited arms. The effective doses of both drugs produced maximal performance impairments 2 hr after IP injection, and no effects after 24 hr. In a second radial arm maze task where only 4 arms were baited, CPP (10 mg/kg) had a somewhat greater effect on the number of working memory errors than on reference memory errors. MK-801 (0.1, 0.33 mg/kg) had no effects on either this task or on a task involving a 1-hr delay between correct choices 4 and 5 on the 8 choice task. CPP (10 mg/kg), however, impaired performance on this latter task. These results indicate that doses of NMDA antagonists, sufficient to block hippocampal long-term potentiation, also disrupt radial arm maze performance.

Clinical trials and tribulations: implementation processes in schizophrenia research outcome.

This article focuses on an area in clinical drug trials for new antipsychotic medications for the treatment of schizophrenia which has not received sufficient attention in the literature: the day-to-day implementation tasks performed by research staff which have potential effects on study results. Implementation tasks are viewed as dynamic processes involving interactions among research and nonresearch staff, patients, families, and pharmaceutical company staff. Research-related demands and possible sources of stress for all participants in the process, such as recruiting and maintaining patients in studies, are discussed. Suggestions are offered for increasing the ease of participation. Further investigation is called for in several areas including variability in the effectiveness of research teams and in the rarely discussed interactions between site staff and pharmaceutical company personnel, as they may affect research outcomes. It is posited that increased knowledge about implementation processes in schizophrenia drug development is needed to more fully understand study results and to enhance patients' and their families' willingness to participate.

Safe sex and first-episode schizophrenia.

The need for educating patients about the dangers of unprotected sexual activity is well documented in the literature. Using clinical examples, the authors describe safe-sex strategies for patients experiencing their first episode of schizophrenia. Interventions are based on a 2-year experience of working in a hospital-based treatment and research project with 68 patients. Strategies that begin in the healing phase of schizophrenia take place in both individual and group sessions. First-episode patients are encouraged to speak explicitly about their sex-related behaviors, and HIV testing is suggested when needed. The goal of this approach is to emphasize safe-sex/HIV prevention strategies within a framework of good clinical practice.