Early prediction of adverse events in enhanced recovery based upon the host systemic inflammatory response.

AIM: Early identification of patients experiencing postoperative complications is imperative for successful management. C-reactive protein (CRP) is a nonspecific marker of inflammation used in many specialties to monitor patient condition. The role of CRP measurement early in the elective postoperative colorectal patient is unclear, particularly in the context of enhanced recovery (ERAS). METHODS: Five hundred and thirty-three consecutive patients who underwent elective colorectal surgery between October 2008 and October 2010 within an established ERAS programme were studied. Patients were separated into a development group of 265 patients and a validation group of 268 patients by chronological order. CRP and white cell count were added to a prospectively maintained ERAS database. The primary outcome of the study was all adverse events (including infective complications, postoperative organ dysfunction and prolonged length of stay) during the initial hospital admission. Significant predictors for adverse events on univariate analysis were submitted to multivariate regression analysis and the resulting model applied to the validation group. The validity and predictive accuracy of the regression model was assessed using receiver operating characteristic curve/area under the curve (AUC) analysis. RESULTS: CRP levels >150 mg/l on postoperative day 2 and a rising CRP on day 3 were independently associated with all adverse events during the hospital admission. A weighted model was applied to the validation group yielding an AUC of 0.65 (95% CI 0.58-0.73) indicating, at best, modest discrimination and predictive accuracy for adverse events. CONCLUSION: Measurement of CRP in patients after elective colorectal surgery in the first few days after surgery within ERAS can assist in identifying those at risk of adverse events and a prolonged hospital stay. A CRP value of >150 mg/l on day 2 and a rising CRP on day 3 should alert the surgeon to an increased likelihood of such events.

Requirement for postoperative imaging in an enhanced recovery programme.

AIM: Enhanced recovery after surgery (ERAS) produces benefits to patients by reducing the length of hospital stay and morbidity. Its effect on nursing and physiotherapy workload has been studied, but the demand upon radiology is unclear. We aimed to determine radiology use to understand possible hidden expenditure not included in existing ERAS cost-effectiveness analyses. METHOD: Two-hundred and sixty-five patients from a prospective multidimensional ERAS database were retrospectively assessed for postoperative radiology use. All had undergone colorectal surgery within an established ERAS programme from 2008 to 2009, with all data prospectively recorded. Laparoscopy was offered for all primary colon and rectal resections. All adverse events, including gut dysfunction, surgical site infection and reoperation, were assessed. All radiology within 30 days of surgery was recorded. RESULTS: Radiology data were absent in 12 patients, leaving 253 for analysis. Postoperative radiology was used in 71 (28%) patients, and 41 (16%) had CT of the abdomen and pelvis (A/P) within 30 days of surgery. In 33 (13%) patients this was required during the primary admission, including 30% of patients with any postoperative adverse event. Nine (27%; 3.6% of the whole cohort) of the 33 patients required reoperation. No patient required interventional radiology. The median time to CT (A/P) during primary admission was 5 (interquartile range, 3-8) days. Eight (3%) patients had CT (A/P) after readmission with one reoperation. Forty (16%) patients underwent plain radiology (chest or abdominal) and six (2%) had abdominal ultrasound. Using general estimates of CT and plain radiology total costs, these data suggest an overall radiology cost of over £22,000, amounting to a radiology cost of £90 per ERAS patient. CONCLUSION: Postoperative radiology is required in a significant proportion of ERAS patients, potentially reflecting a low threshold to investigate in the presence of an adverse event. Very few require subsequent intervention. Radiology costs incurred with ERAS should be considered in future economic analyses.

Anxiety-related behavioral inhibition in rats: a model to examine mechanisms underlying the risk to develop stress-related psychopathology.

Behavioral inhibition (BI) is an adaptive defensive response to threat; however, children who display extreme BI as a stable trait are at risk for development of anxiety disorders and depression. The present study validates a rodent model of BI based on an ethologically relevant predator exposure paradigm. We show that individual differences in rat BI are stable and trait-like from adolescence into adulthood. Using in situ hybridization to quantify expression of the immediate early genes homer1a and fos as measures of neuronal activation, we show that individual differences in BI are correlated with the activation of various stress-responsive brain regions that include the paraventricular nucleus of the hypothalamus and CA3 region of the hippocampus. Further supporting the concept that threat-induced BI in rodents reflects levels of anxiety, we also show that BI is decreased by administration of the anxiolytic, diazepam. Finally, we developed criteria for identifying extreme BI animals that are stable in their expression of high levels of BI and also show that high BI (HBI) individuals exhibit maladaptive appetitive responses following stress exposure. These findings support the use of predator threat as a stimulus and HBI rats as a model to study mechanisms underlying extreme and stable BI in humans.

Schizophrenia in general practice: a national survey of general practitioners in Ireland.

BACKGROUND: Chronic schizophrenia is challenging to manage in primary care. AIMS: We sought to establish the views of General Practitioners about managing patients with chronic schizophrenia in primary care. METHODS: A cross-sectional, postal survey questionnaire of a randomly selected sample of 20% of GPs was carried out. RESULTS: Most GPs (97.2%) have at least one person with schizophrenia attending their practice. A substantial number of GPs (22.2%) treat cases of schizophrenia without specialist input following an initial referral to psychiatric services. Almost all (88.7%) advised patients who had experienced multiple relapses to remain on medication indefinitely. One third of GPs reported that they always experience difficulties managing patients with schizophrenia in their practice. Non-adherence with prescribed medication and loss to follow-up were the commonest impediments to treatment encountered. CONCLUSION: GPs require appropriate back up from specialist services to enable their management of chronic schizophrenia.

Life supporting first aid (LSFA) teaching to Brazilians by television spots.

Accidents in developing countries are frequent and have high mortality and morbidity rates. In Brazil, in 1995-1996, the year of this study, life supporting first aid (LSFA), which includes cardiopulmonary resuscitation (CPR) basic life support (BLS) was not taught in schools. With the population of 165 million, the only way to teach the adult population on a large scale would be by television (TV), that is widely viewed. This study compares two groups of factory employees - 86 controls without TV exposure to LSFA and 116 exposed to brief LSFA skill demonstrations on TV. Their ability to acquire eight LSFA skills was evaluated: external hemorrhage control; immobilization of a suspected forearm fracture; treatment of a skin burn by cold flush; body alignment after a fall; positioning for shock and coma; airway control by backward tilt of the head; and CPR (steps A-B-C). Simulated skill performance on the evaluating nurse or manikin was tested at 1 week, 1 month, and 13 months. In the control group, 1-31% performed individual skills correctly; as compared to 9-96% of the television group (P<0.001). There was excellent retention over 13 months. Over 50% of the television group performed correctly five of the eight skills, including positioning and hemorrhage control. Television viewing increased correct airway control performance from 5 to 25% of trainees, while it remained at 3% in the control group. CPR-ABC performance, however, was very poor in both groups. We conclude that a significant proportion of factory workers can acquire simple LSFA skills through television viewing alone, except for the skill acquisition of CPR steps B (mouth-to-mouth ventilation) and C (external chest compressions) which need coached manikin practice.

Na(+)-K(+)-ATPase-mediated basolateral rubidium uptake in the maturing rabbit cortical collecting duct.

Within the renal cortical collecting duct (CCD), transepithelial Na(+) absorption and K(+) secretion are linked to basolateral Na(+)-K(+)-ATPase activity. Our purpose was to examine the developmental changes in basolateral Na(+)-K(+)-ATPase-mediated (86)rubidium (Rb) uptake, its inhibitor sensitivity and relationship to pump hydrolytic activity and Na(+) transport. Multiple CCDs ( approximately 6 mm) from maturing rabbits were affixed to coverslips, preincubated at 37 degrees C for 10 min (+/-1-2.5 mM ouabain or 10 or 100 micro M Schering-28080, an inhibitor of H(+)-K(+)-ATPase), and then transferred to prewarmed incubation solution containing tracer amounts of (86)Rb (+/-inhibitors). After 1 min at 37 degrees C, tubular samples were rinsed and permeabilized and isotope counts were measured to calculate basolateral Rb uptake. Ouabain-inhibitable Rb uptake, an index of basolateral Na(+)-K(+) pump activity, increased approximately 3-fold during the 1st 8 wk of postnatal life (P < 0.03). The approximately 2-fold increase in absolute rate of Rb uptake between 1 and 6 wk (2.64 +/- 0.45 to 5.02 +/- 0.32 pmol. min(-1). mm(-1)) did not reach statistical significance. The rate of basolateral Rb uptake increased further after the 6th wk of life to 7.29 +/- 0.53 pmol. min(-1). mm(-1) in adult animals (P < 0.03 vs. 6 wk). Schering-28080 failed to inhibit Rb uptake, implying that functional H(+)-K(+)-ATPase is absent at the basolateral membrane. Na(+)-K(+)-ATPase hydrolytic activity, determined by using a microassay that measured inorganic phosphate release from [gamma-(32)P]ATP under maximum velocity (V(max)) conditions, also increased in the differentiating CCD (from 316.2 +/- 44.4 pmol. h(-1). mm(-1) at 2 wk to 555.9 +/- 105.1 at 4 wk to 789.7 +/- 145.0 at 6 wk; r = 1.0 by linear regression analysis; P < 0.005). The parallel approximately 2.5-fold increases in Na(+)-K(+)-ATPase activity and ouabain-sensitive Rb uptake between 2- and 6-wk postnatal age suggest that the developmental increase in basolateral transport capacity is due predominantly to an increase in enzyme abundance. The signals mediating the developmental increase in Na(+)-K(+)-ATPase activity in the CCD remain to be defined.

Migraine in the athlete.

Migraine in the athlete may occur secondary to effort, prolonged exertion, or trauma or as a posttraumatic event. The chemistry is probably akin to that of spontaneous migraine. The purpose of this discussion is to outline the differential diagnosis of the athlete presenting with headache. Appropriate treatment can enhance athletic performance and enable the migraineur to participate in athletic endeavors.

The dangerous nature of intimate relationship stalking: threats, violence, and associated risk factors.

Although previous studies of forensic and law enforcement stalking populations (Harmon, Rosner, & Owens, 1995; Meloy & Gothard, 1995; Zona, Sharma, & Lane, 1993) agree that the degree of intimacy of the victim-suspect relationship is an important factor in stalking cases, they have not conducted in-depth analyses of this variable. This study compared 223 intimate (n=135) and non-intimate (n=88) stalking cases managed by the Los Angeles Police Department's Threat Management Unit. A path analysis revealed a significant relationship between the stalkers' intimate versus non-intimate status and violence committed toward persons and property. This relationship was positively influenced by the suspect's level of proximity to the victim and threats toward the victim and property, but not influenced by suspect's criminal, psychiatric, and domestic violence histories. Overall, intimate relationship stalkers used more dangerous stalking behaviors than non-intimate relationship stalkers. Risk factors for assessing dangerousness of stalkers are discussed.

Preservaçäo da veia safena magna em cirurgia de varizes: resultados tardios / Preservation of the great saphenous vein in varicose veins surgery, late results

Foram operados 185 pacientes portadores de varizes primárias dos membros inferiores no período de 1983 a 1988. A conduta cirúrgica, em especial a fleboextraçäo das veias safenas internas, foi determinada a partir do exame pré-operatório dessas veias com Doppler, durante manobra de Brodie-Trendelenburg. Em 1991, ou seja, entre dois e sete anos após a cirurgia, os pacientes foram convocados para revisäo com objetivo de avaliar a presença de varizes recidivadas. Foi possível examinar 80 pacientes, obsvando-se bons resultados em 87,69 por cento das extremidades em que se preservaram as veias safenas. Conclui-se pela validade desse procedimento nos pacientes em que as veias safenas se apresentam normais ao exame pré-operatório com Doppler.

The seat belt syndrome in children.

Lap belts, fitted to the centre seats of Australian cars for the past 22 years, have come under criticism as being injurious to children. The weight of evidence is that lap belts provide substantial protection, though less than three-point belts. A specific injury, the seat belt syndrome (SBS), to abdominal viscera and/or lumbar spine has been particularly associated with lap belts, an association confirmed by a hospital-based study in Melbourne. Roadside observations of belt use and Transport Accident Commission claims permitted the calculation of the incidence of SBS and the relative risks of SBS by seated position. The centre rear seat (lap belt) carried about twice the risk of SBS as outboard rear seats (three-point belts), which in turn have 2.7 times the risk of the outboard front seat. The number of SBS cases in Victoria has increased with penetration of the car fleet by 1971 and later cars. Suggestions are made for improvements in the restraint system.

beta-Carotene transport in human lipoproteins. Comparisons with a-tocopherol.

The purpose of this study was to investigate the temporal relationships of the transport of beta-carotene in human lipoproteins. We administered 60 mg beta-carotene with breakfast to nine fasting subjects, then blood samples were collected at intervals of up to 75 h, lipoproteins were isolated, and beta-carotene was quantitated. beta-Carotene concentrations in chylomicrons and very low density lipoproteins (VLDL) peaked at 6 and 9 h, respectively. Nonetheless, at all time points the majority of plasma beta-carotene was contained in low density lipoproteins (LDL), while high density lipoproteins (HDL) carried a smaller portion (at 24 h, 73 +/- 8% in LDL as compared with 23 +/- 5% in HDL). In three subjects, transport of beta-carotene was compared with the results of earlier studies on the transport of stereoisomers of alpha-tocopherol. Unlike plasma RRR-alpha-tocopherol concentrations, which are maintained by the preferential incorporation of RRR-alpha-tocopherol into VLDL by the liver, beta-carotene increased and decreased in VLDL similarly to SRR-alpha-tocopherol, a stereoisomer whose concentrations are not maintained in plasma. In conclusion, beta-carotene is primarily transported in the plasma in LDL, but its incorporation by the liver into lipoproteins does not appear to be enhanced.

Bactericidal/permeability-increasing protein and lipopolysaccharide (LPS)-binding protein. LPS binding properties and effects on LPS-mediated cell activation.

We have previously shown that human bactericidal/permeability-increasing protein (BPI) is able to inhibit serum-dependent lipopolysaccharide (LPS)-mediated activation of human monocytes and neutrophils in vitro, and to counteract the lethal effects of LPS challenge in vivo. Lipopolysaccharide-binding protein (LBP) is a serum protein which participates in LPS-mediated activation of cells (Tobias, P. S., Mathison, J., Mintz, D., Lee, J. D., Kravchenko, V., Kato, K., Pugin, J., and Ulevitch, R. J. (1992) Am. J. Respir. Cell. Mol. Biol. 7, 239-245). We have proposed that BPI functions in a negative feedback loop which opposes this activation (Marra, M. N., Wilde, C. G., Collins, M. S., Snable, J. L., Thornton, M. B., and Scott, R. W. (1992) J. Immunol. 148, 532-537). We have now cloned and expressed recombinant forms of human BPI and LBP. Here we demonstrate that purified recombinant human LBP can replace the serum requirement for both LPS binding to human monocytes and LPS-mediated secretion of tumor necrosis factor alpha from these cells. These activities of LBP are inhibited by a neutralizing anti-CD14 monoclonal antibody. We further demonstrate that purified recombinant human BPI can inhibit LBP-mediated LPS binding to cells and their subsequent activation. Comparison of the LPS binding properties of BPI and LBP in enzyme-linked immunosorbent type assays and in the Limulus amebocyte lysate assay suggest that BPI has a stronger affinity for LPS than does LBP. Direct competition between BPI and LBP for LPS may explain the inhibition by BPI of the proinflammatory effects of LBP in the presence of LPS.

The effectiveness of bicyclist helmets: a study of 1710 casualties.

During the 1980s, a sustained campaign increased the rates of helmet use of Victorian bicyclists. The efficacy of helmet use was evaluated by comparison of crashes and injuries (AIS-1985) in 366 helmeted (261 Australian Standard approved and 105 non-approved) and 1344 unhelmeted casualties treated from 1987 through 1989 at Melbourne and Geelong hospitals or dying before hospitalization. Head injury (HI) occurred in 21.1% of wearers of approved helmets and in 34.8% of non-wearers (p < 0.001). The AIS scores were decreased for wearers of approved helmets (p < 0.001), face injuries were reduced (p < 0.01), and extremity/pelvic girdle injuries increased (p < 0.001) and the overall risk of HI was reduced by at least 39% and face injury by 28%. When casualties with dislodged helmets were excluded, HI was reduced 45% by approved helmets. Head injury reduction by helmets, although substantial, was less than that found in a similar study in Seattle, Washington.

Studies on the transfer of tocopherol between lipoproteins.

The net transfer of labeled alpha-tocopherol from donor to acceptor lipoproteins at physiological concentrations was investigated. Labeled lipoproteins were isolated i) following in vitro addition of [3,4-3H] all rac-alpha-tocopherol to plasma, or ii) from plasma obtained 12-16 h after ingestion by normal subjects of an oral dose (100 mg each) of 2R,4'R,8'R-alpha-[5,7-(C2H3)2]tocopheryl acetate and 2S,4'R,'R-alpha-[5-C2H3]tocopheryl acetate. A constant amount (on a protein basis) of labeled lipoprotein was incubated with an increasing amount of unlabeled acceptor lipoprotein for 2 h at 37 degrees C. No discrimination between stereoisomers of alpha-tocopherol was detected. Labeled VLDL and labeled LDL (very low and low density lipoproteins, respectively) tended to retain their labeled tocopherol. Labeled high density lipoproteins (HDL) readily transferred the labeled tocopherol to VLDL (> 60% transferred), while the transfer to LDL was dependent upon the ratio of labeled HDL/LDL with a lower net transfer at higher ratios. This dependency of the distribution of tocopherol upon the ratio of HDL/LDL was also observed in vivo. The tocopherol/mg HDL protein was measured in 11 subjects with varying HDL levels. As the % HDL in the plasma increased from 14 to 50%, the tocopherol/HDL protein also increased (r2 = 0.37, P < 0.05).

Whipple's disease presenting with isolated neurological symptoms. Case report.

Whipple's disease is infrequently considered in the differential diagnosis of patients presenting with progressive neurological deterioration. This is in part a result of the relative rarity of this entity and in part due to the more frequent initial presentation of the disease with gastrointestinal, musculoskeletal, or cardiovascular symptoms. A case is described in which the neurological symptoms of progressive dementia and weakness were seen in the relative absence of non-neurological symptomatology. The diagnosis of Whipple's disease was made from a brain biopsy. The neuropathology of Whipple's disease of the central nervous system is described and the importance of considering it as a treatable entity in the differential diagnosis of progressive neurological deterioration, despite the absence of systemic symptomatology, is stressed.

Social epidemiology: directions for the future in academic and "shoe-leather" risk analysis.

In the past, social epidemiology has been a field of interest to only a few professionals, notably sociologists and a select few epidemiologists. Expansion of the scope of epidemiology beyond infectious diseases and a few chronic diseases has made social epidemiology vitally important in the work of a host of professionals in public health and preventive medicine. These include persons doing risk analysis, persons working in environmental and occupational health, health educators, and persons working in institutions such as labor unions and schools which mediate the effects of risk factors upon population groups. With the expansion of the field, it is becoming apparent that the interrelationships among social risk factors are complex. Some social factors are both predictors of health status and outcome factors. This complexity will require new analytic methods, some of which are outside the present repertoire of most epidemiologists and biostatisticians. This paper examines the changing scope and impact of social epidemiology and suggests directions for the future of teaching and research in the field. If these new directions, guide research and teaching in the field, public health professionals will be able to bring a host of newly acquired skills to their "shoe-leather" epidemiology. Using those skills will require broad interdisciplinary cooperation in health promotion and disease prevention.