Enhanced recovery from surgery in the UK: an audit of the enhanced recovery partnership programme 2009-2012.

BACKGROUND: The UK Department of Health Enhanced Recovery Partnership Programme collected data on 24 513 surgical patients in the UK from 2009-2012. Enhanced Recovery is an approach to major elective surgery aimed at minimizing perioperative stress for the patient. Previous studies have shown Enhanced Recovery to be associated with reduced hospital length of stay and perioperative morbidity. METHODS: In this national clinical audit, National Health Service hospitals in the UK were invited to submit patient-level data. The data regarding length of stay and compliance with each element of Enhanced Recovery protocols for colorectal, orthopaedic, urological and gynaecological surgery patients were analysed. The relationship between Enhanced Recovery protocol compliance and length of stay was measured. RESULTS: From 16 267 patients from 61 hospital trusts, three out of four surgical specialties showed Enhanced Recovery, compliance being weakly associated with shorter length of stay (correlation coefficients -0.18, -0.14, -0.25 in colorectal, orthopaedics and gynaecology respectively). At a cut-off of 80% compliance, good compliance was associated with two, one and three day reductions in median length of stay respectively in colorectal, orthopaedic and urological surgeries, with no saving in gynaecology. CONCLUSIONS: This study is the largest assessment of the relationship between Enhanced Recovery protocol compliance and outcome in four surgical specialties. The data suggest that higher compliance with an Enhanced Recovery protocol has a weak association with shorter length of stay. This suggests that changes in process, resulting from highly protocolised pathways, may be as important in reducing perioperative length of stay as any individual element of Enhanced Recovery protocols in isolation.

Development and validation of the Surgical Outcome Risk Tool (SORT).

BACKGROUND: Existing risk stratification tools have limitations and clinical experience suggests they are not used routinely. The aim of this study was to develop and validate a preoperative risk stratification tool to predict 30-day mortality after non-cardiac surgery in adults by analysis of data from the observational National Confidential Enquiry into Patient Outcome and Death (NCEPOD) Knowing the Risk study. METHODS: The data set was split into derivation and validation cohorts. Logistic regression was used to construct a model in the derivation cohort to create the Surgical Outcome Risk Tool (SORT), which was tested in the validation cohort. RESULTS: Prospective data for 19 097 cases in 326 hospitals were obtained from the NCEPOD study. Following exclusion of 2309, details of 16 788 patients were analysed (derivation cohort 11 219, validation cohort 5569). A model of 45 risk factors was refined on repeated regression analyses to develop a model comprising six variables: American Society of Anesthesiologists Physical Status (ASA-PS) grade, urgency of surgery (expedited, urgent, immediate), high-risk surgical specialty (gastrointestinal, thoracic, vascular), surgical severity (from minor to complex major), cancer and age 65 years or over. In the validation cohort, the SORT was well calibrated and demonstrated better discrimination than the ASA-PS and Surgical Risk Scale; areas under the receiver operating characteristic (ROC) curve were 0·91 (95 per cent c.i. 0·88 to 0·94), 0·87 (0·84 to 0·91) and 0·88 (0·84 to 0·92) respectively (P < 0·001). CONCLUSION: The SORT allows rapid and simple data entry of six preoperative variables, and provides a percentage mortality risk for individuals undergoing surgery.

Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum.

The cytosolic coat-protein complex COP-I interacts with cytoplasmic 'retrieval' signals present in membrane proteins that cycle between the endoplasmic reticulum (ER) and the Golgi complex, and is required for both anterograde and retrograde transport in the secretory pathway. Here we study the role of COP-I in Golgi-to-ER transport of several distinct marker molecules. Microinjection of anti-COP-I antibodies inhibits retrieval of the lectin-like molecule ERGIC-53 and of the KDEL receptor from the Golgi to the ER. Transport to the ER of protein toxins, which contain a sequence that is recognized by the KDEL receptor, is also inhibited. In contrast, microinjection of anti-COP-I antibodies or expression of a GTP-restricted Arf-1 mutant does not interfere with Golgi-to-ER transport of Shiga toxin/Shiga-like toxin-1 or with the apparent recycling to the ER of Golgi-resident glycosylation enzymes. Overexpression of a GDP-restricted mutant of Rab6 blocks transport to the ER of Shiga toxin/Shiga-like toxin-1 and glycosylation enzymes, but not of ERGIC-53, the KDEL receptor or KDEL-containing toxins. These data indicate the existence of at least two distinct pathways for Golgi-to-ER transport, one COP-I dependent and the other COP-I independent. The COP-I-independent pathway is specifically regulated by Rab6 and is used by Golgi glycosylation enzymes and Shiga toxin/Shiga-like toxin-1.

Pollution monitoring of puget sound with honey bees.

To show that honey bees are effective biological monitors of environmental contaminants over large geographic areas, beekeepers of Puget Sound, Washington, collected pollen and bees for chemical analysis. From these data, kriging maps of arsenic, cadmium, and fluoride were generated. Results, based on actual concentrations of contaminants in bee tissues, show that the greatest concentrations of contaminants occur close to Commencement Bay and that honey bees are effective as large-scale monitors.

The Spir actin organizers are involved in vesicle transport processes.

The p150-Spir protein, which was discovered as a phosphorylation target of the Jun N-terminal kinase, is an essential regulator of the polarization of the Drosophila oocyte. Spir proteins are highly conserved between species and belong to the family of Wiskott-Aldrich homology region 2 (WH2) proteins involved in actin organization. The C-terminal region of Spir encodes a zinc finger structure highly homologous to FYVE motifs. A region with high homology between the Spir family proteins is located adjacent (N-terminal) to the modified FYVE domain and is designated as "Spir-box." The Spir-box has sequence similarity to a region of rabphilin-3A, which mediates interaction with the small GTPase Rab3A. Coexpression of p150-Spir and green fluorescent protein-tagged Rab GTPases in NIH 3T3 cells revealed that the Spir protein colocalized specifically with the Rab11 GTPase, which is localized at the trans-Golgi network (TGN), post-Golgi vesicles, and the recycling endosome. The distinct Spir localization pattern was dependent on the integrity of the modified FYVE finger motif and the Spir-box. Overexpression of a mouse Spir-1 dominant interfering mutant strongly inhibited the transport of the vesicular stomatitis virus G (VSV G) protein to the plasma membrane. The viral protein was arrested in membrane structures, largely colocalizing with the TGN marker TGN46. Our findings that the Spir actin organizer is targeted to intracellular membrane structures by its modified FYVE zinc finger and is involved in vesicle transport processes provide a novel link between actin organization and intracellular transport.

Correct and incorrect use of child restraints: results from an urban survey in New Zealand.

This study describes the incorrect use of child restraints among car drivers with young children and examines factors that may influence their misuse. A cross-sectional survey was undertaken in supermarket car parks with car drivers travelling with children under the age of 8 years. The main measure was errors in child restraint use. Short interviews were conducted with 1113 drivers with a close inspection of the child restraints used in the vehicles. Only 4% of children were unrestrained but 64% of drivers made at least one error in restraint use. Most respondents thought using a restraint was easy, but 65% of these drivers made at least one error. Child restraints are used, but many are incorrectly fitted and/or have the child incorrectly placed in them. Correct use is a moderately complex task. Restraint systems need to be designed to minimize the opportunity for error and maximize safety.

Accurate and semi-automated analysis of bacterial association with mammalian cells.

To efficiently and accurately quantify the interactions of bacteria with mammalian cells, a reliable fluorescence microscopy assay was developed. Bacteria were engineered to become rapidly and stably fluorescent using Green Fluorescent Protein (GFP) expressed from an inducible Tet promoter. Upon application of the fluorescent bacteria onto a monolayer, extracellular bacteria could be discriminated from intracellular bacteria by antibody staining and microscopy. All bacteria could be detected by GFP expression. External bacteria stained orange, whereas internalised bacteria did not. Internalised bacteria could thus be discriminated from external bacteria by virtue of being green but not orange fluorescent. Image acquisition and counting of various fluorophore-stained entities were accomplished with a high-content screening platform. This allowed for semi-automated and accurate counting of intracellular and extracellular bacteria.

Mortality studies in psychiatry. Should they stop or proceed?

Psychiatry as a medical discipline has a special concern for preventing premature deaths in psychiatric patients. Such patients continue to be at excess mortality risk despite changing patterns of causes of death and improvements in the treatment of some diagnostic groups. In this overview of current findings and research trends, we find a continuing need for mortality studies and increased opportunities for integrating these investigations with other longitudinal studies of psychiatric populations.

Subtypes of drug abuse with psychosis. Demographic characteristics, clinical features, and family history.

Hospital records of 72 drug abusers with psychoses (DAP) were analyzed to clarify the relationship between drug abuse and psychosis. Comparison groups included schizophrenics and atypical schizophrenics without drug abuse and drug abusers without psychoses (DA). Compared with DAP in whom psychoses lasted less than six months before admission (DAP-short), drug abusers with psychoses of a longer duration (DAP-long) had more symptoms, more premorbid personality disorders, and greater familial risks of schizophrenia and affective disorder. The DAP-long group resembled atypical schizophrenia for clinical features and family history, whereas the DAP-short group resembled DA for some clinical features and family history. The results indicate that there are several subgroups of DAP. The importance of clinical features and family history in identifying subgroups of DAP was stressed.

Playing conditions, player preparation and rugby injury: a case-control study.

This paper investigates the effect of player preparation, ground conditions and weather conditions upon the injury risk for Rugby Union players. A population-based case-control study was performed using a sample (n= 1043) of New Zealand Rugby Union players aged 16 y and above. Details concerning game preparation (warm-up and usual position), and ground and weather conditions (precipitation, wind and temperature) were obtained from the players. If players were injured during the season (n= 624) they were asked to provide details about the game in which they were last injured. Uninjured players (n= 419) provided details about the last game in which they played. Injuries were more likely to occur when games were played on hard grounds or in calm or warm conditions. Playing out of position and the duration of warming up did not significantly alter the risk of injury. When player preparation, ground and weather conditions, grade, age, playing position and rugby experience were simultaneously controlled for, hard ground and the absence of wind were associated with increased risk. The influence of these factors may be indirect, through adaptation to the conditions in which a game is played.

A family study of sex differences in the diagnosis of atypical schizophrenia.

It has been hypothesized that women are more likely than men to have atypical schizophrenia. Among 984 relatives of patients with typical and atypical schizophrenia, the odds of having atypical schizophrenia did not differ by sex.

Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients.

OBJECTIVE: The factor structures of individual positive and negative symptoms as well as global ratings were examined in a diagnostically heterogeneous group of subjects. METHOD: Subjects were identified through a clinical and family study of patients with major psychoses at a VA medical center and evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. For the examination of global-level factor structures (N = 630), both principal-component analysis and factor analysis with orthogonal rotation were used. Factor analysis was used for the examination of item-level factor structures as well (N = 549). RESULTS: The principal-component analysis of global ratings revealed three factors: negative symptoms, positive symptoms, and disorganization. The factor analysis of global ratings revealed a negative symptom factor and a positive symptom factor. The item-level factor analysis revealed two negative symptom factors (diminished expression and disordered relating), two positive symptom factors (bizarre delusions and auditory hallucinations), and a disorganization factor. CONCLUSIONS: The generation of additional meaningful factors at the item level suggests that important information about symptoms is lost when only global ratings are viewed. Future work should explore clinical and pathological correlates of the more differentiated item-level symptom dimensions.

Ricin A chain utilises the endoplasmic reticulum-associated protein degradation pathway to enter the cytosol of yeast.

Cytotoxic proteins such as ricin A chain (RTA) have target substrates in the cytosol and therefore have to reach this cellular compartment in order to act. RTA is thought to translocate into the cytosol from the lumen of the endoplasmic reticulum (ER), although how it traverses the ER membrane has not been established. Using yeast mutants defective in various aspects of the ER-associated protein degradation (ERAD) pathway, we show that RTA introduced into the yeast ER subverts this pathway to enter the cytosol via the Sec61p translocon. A significant proportion of the exported RTA avoided proteasomal degradation. These data are consistent with the contention that the RTA component from ricin endocytosed by mammalian cells may likewise exploit ERAD to translocate into the cytosol.

Physical diseases in schizophrenia and affective disorder.

Studies of the increased or decreased risk of specific physical diseases in patients with schizophrenia and affective disorder are reviewed. Existing data suggest further examination of the following relationships: (1) the presence in schizophrenics of increased incidence of gastrointestinal cancer and of cardiovascular and infectious diseases, and of decreased incidence of lung cancer and rheumatoid arthritis; and (2) the increased incidence of circulatory, respiratory, and atopic diseases, and of diabetes mellitus among patients with major affective disorder. A majority of the studies reviewed failed to meet methodologic standards necessary to provide conclusive evidence. An ongoing research project which generally meets these standards, the Oxford Record Linkage Study, is described.

Schizoaffective disorder: concept and reality.

A wide variety of concepts have been proposed to account for schizoaffective psychoses. Presenting a mixture of schizophrenic and affective symptoms, these psychoses have long defied classification in the usual scheme of the two major diagnostic categories, schizophrenia and major affective disorder. Empirical findings are often contradictory, and have sometimes supported the classification of schizoaffective disorder with schizophrenia, and, more recently, with major affective disorders. An alternative hypothesis is that schizoaffective disorder is fundamentally heterogeneous, and that research efforts should be directed toward the identification of homogeneous subtypes. To illustrate the latter research strategy, we describe our current research program of long-term followup and family studies of patients with schizoaffective psychoses and other atypical psychoses. Extensive data have been obtained using blind, structured psychiatric interviews with probands after 30 to 40 years of followup, and with their first degree relatives. In the same way, followup and family data were obtained for patients who met research criteria for schizophrenia, mania, and depression, and for matched surgical controls. By comparing these groups of "typical" psychotic patients with the schizoaffective patients, we can select homogeneous subgroups of schizoaffective patients and analyze their characteristics to refine clinical and research criteria for the differential diagnosis of schizoaffective subtypes.

Mortality among patients with schizophrenia.

Results from a 40-year followup study of psychotic patients are presented to illustrate some of the major findings and unanswered questions about excess mortality in schizophrenia and to suggest analytical approaches that take full account of the potential effects of sample heterogeneity. In this study, hospital-diagnosed schizophrenia patients were at increased mortality risk whether or not they met research criteria for schizophrenia. In addition, mortality outcomes of several major diagnostic groups were similar despite substantial clinical and demographic differences between the groups at baseline. These results suggest that both diagnosis-specific and nondiagnostic factors are needed to account for excess mortality in patients with major psychiatric disorders. The issue of heterogeneity is also crucial for the clinical purposes of predicting and ultimately reducing the mortality risk of psychiatric patients, for example, in delineating profiles of high-risk patients who are not necessarily typical of other patients with the same diagnosis.

Outcome studies of schizoaffective disorders.

Outcome studies of schizoaffective disorder have taught us much about the long-term consequences of the syndrome, and they have provided some indication of the potential usefulness of maintaining "schizoaffective disorder" as a diagnostic category separate from schizophrenia and major affective disorder. In a review of outcome studies that compared schizoaffective patients to schizophrenic or affective patients, we found consistent results despite wide variations in diagnostic criteria, length of followup, and demographic characteristics. Global measures of outcome show that schizophrenic patients are more impaired than schizoaffective patients, who in turn are more impaired than affective patients. However, studies of specific outcome domains such as symptomatology, social functioning, and occupational functioning indicate that schizoaffective disorder is heterogeneous and that subtyping by polarity (e.g., schizoaffective-manic vs. schizoaffective-depressed) accounts for some of this variance. The consistency of these findings in the face of methodological variability suggests that it would be premature to classify schizoaffective patients with schizophrenia or affective disorder, but also that strict diagnostic criteria for schizoaffective disorder are at best preliminary and need to be thoroughly validated.

The role of gender in identifying subtypes of schizophrenia: a latent class analytic approach.

Past literature suggests that schizophrenic men and women may be at different risks for developing different subtypes of schizophrenia. This hypothesis was tested using data from the well-known retrospective cohort family studies, the Iowa 500 and the Iowa non-500. The sample consisted of 171 male and 161 female DSM-III schizophrenic patients and 713 of their first-degree relatives. First, bivariate tests for gender differences were conducted regarding family morbidity, age of onset, premorbid history, season of birth, and expression of deficit and affective symptoms. Restricted maximum likelihood latent class analysis was then used to test whether there was a subgroup of schizophrenic men who were more likely to have a low familial risk for schizophrenia or schizophrenia spectrum disorders, deficit symptoms, poor premorbid history, and birth in the winter months, suggesting possible early environmental insults, compared to schizophrenic women. Results showed that although men were more likely to meet these criteria, women also met them, thus suggesting gender differences in the prevalence of the subtype. Schizophrenic women were more likely to express a form of the illness characterized by dysphoria, persecutory delusions, and a higher family morbidity risk for schizophrenia than schizophrenic men. Results for spectrum disorders among relatives were equivocal with regard to gender.

Educating future physicians for Ontario.

In 1987, Ontario's physicians conducted a strike, ultimately not successful, over the issue of "extra billing." The fact that the Ontario public did not support this action reflected a major gap between the profession's view of itself and the public's view of the profession. In 1990, the province's five medical schools launched a collaborative project to determine more specifically what the people of Ontario expect of their physicians, and how the programs that prepare future physicians should be changed in response. The authors report on the first five years of that ongoing project. Consumer groups were asked to state their views concerning the current roles of physicians, future trends that would affect these roles, changes in roles they wished to see, and suggestions for changes in medical education. Methods used included focus groups, key informant interviews, an extensive literature review, and surveys, including a survey of health professionals. Concurrently, inter-university working groups prepared tools and strategies for strengthening faculty development, assessing student performance, and preparing future leadership for Ontario's medical education system. Eight specific physician roles were identified: medical expert, communicator, collaborator, health advocate, learner, manager ("gatekeeper"), scholar, and "physician as person." Educational strategies to help medical students learn to assume these eight roles were then incorporated into the curricula of the five participating medical schools. The authors conclude that the project shows that it is feasible to learn specifically what society expects of its physicians, to integrate this knowledge into the process of medical education reform, and to implement major curriculum changes through a collaborative, multi-institutional consortium within a single geopolitical jurisdiction.

Evaluating Tackling Rugby Injury: the pilot phase for monitoring injury.

OBJECTIVE: To assess the suitability of two previously unused data sources for monitoring rugby injury throughout New Zealand. METHOD: Interviews were conducted with respondents sampled from players registered with the Rugby Football Unions (RFUs) and players claiming for rugby injuries from the Accident Rehabilitation and Compensation Insurance Corporation (ACC) in Auckland and Dunedin. RESULTS: Of the 500 RFU players sampled, 63% were interviewed and of these 39 (12%) had been injured playing rugby union. Of the 456 ACC claimants sampled, 66% were interviewed and 265 (88%) had been injured playing rugby union. CONCLUSION: Identifying injured players through ACC claims was more efficient, both procedurally and because a smaller sample size was required to detect changes in incidence. IMPLICATIONS: With no routine surveillance of sports injury being undertaken, recording sporting codes in national injury surveillance systems would assist the monitoring of sports injury.