Enhanced recovery protocols in total joint arthroplasty: a review of the literature and their implementation.

BACKGROUND: During recent years, there has been an exponential demand for joint arthroplasty, which has coincided with the global economic recession. In response, the management of patients following arthroplasty is continuously evolving, with the average inpatient length of stay decreasing from weeks to days, and more recently, we have witnessed the development of "outpatient arthroplasty" as a novel concept which aims to address the high volume of patients. The reduction in length of stay has been made possible via implementation of "enhanced recovery programmes" encompassing each stage of the patient journey. Such programmes have aimed to maximise efficiency, whilst maintaining patient satisfaction and achieving exceptional functional outcomes. OBJECTIVE: We have undertaken a thorough review the literature in relation to enhanced recovery programmes (ERPs) and the research that has underpinned individual elements of enhanced recovery. A literature search of enhanced recovery protocols was carried out using PubMed, Cochrane, Embase and OVID. No language restrictions were imposed on the search. REVIEW: ERPs represent a multifactorial framework which may be subdivided into several phases. Pre-operative education programmes, outpatient consultation, pre-anaesthetic assessment, pre-procedural physiotherapy, day-of-surgery admission, pre-operative medications, type of anaesthesia, blood loss reduction protocols, multimodal analgesia delivery, day-of-surgery mobilisation, thromboembolic prophylaxis and ongoing rehabilitation are essential in enhanced recovery. CONCLUSION: These successful strategies have streamlined the patient pathway of arthroplasty surgery in a cost-effective manner, whilst reducing length of hospital stay and maintaining patient outcomes. Further studies are required to appropriately quantify the impact of individual variables and development of an internationally agreed ERP.

Modeling Intermittent Running from a Single-visit Field Test.

This study assessed whether the distance-time relationship could be modeled to predict time to exhaustion (TTE) during intermittent running. 13 male distance runners (age: 33±14 years) completed a field test and 3 interval tests on an outdoor 400 m athletic track. Field-tests involved trials over 3 600 m, 2 400 m and 1 200 m with a 30-min rest between each run. Interval tests consisted of: 1 000 m at 107% of CS with 200 m at 95% CS; 600 m at 110% of CS with 200 m at 90% CS; 200 m at 150% of CS with 200 m at 80% CS. Interval sessions were separated by 24 h recovery. Field-test CS and D' were applied to linear and non-linear models to estimate the point of interval session termination. Actual and predicted TTE using the linear model were not significantly different in the 1 000 m and 600 m trials. Actual TTE was significantly lower (P=0.01) than predicted TTE in the 200 m trial. Typical error was high across the trials (range 334-1 709 s). The mean balance of D' remaining at interval session termination was significantly lower when estimated from the non-linear model (-21.2 vs. 13.4 m, P<0.01), however no closer to zero than the linear model. Neither the linear or non-linear model could closely predict TTE during intermittent running.

Effect of chemopreventive agents on separate stages of progression of benzo[alpha]pyrene induced lung tumors in A/J mice.

The effects of aerosol budesonide and dietary myo-inositol on progression of benzo[alpha]pyrene (B[alpha]P) induced carcinogenesis were studied in A/J mouse lung. First, we determined when to intervene in the carcinogenesis process by exposing several animals to B[alpha]P at 100 and 150 mg/kg of body wt. Groups of these animals were necropsied from 1 to 36 weeks post-carcinogen. The presence of different categories of lung tumors was noted over the 36 week time period. Hyperplasia first appeared approximately 6 weeks post-carcinogen followed by adenoma at 9 weeks, then by carcinoma at 26 weeks. From this temporal sequence we determined we could test for effects of preventive agents on progression to hyperplasia by intervening at 3 weeks, for effects on progression to adenoma by intervening at 6 weeks and for effects on progression to carcinoma by intervention at 12 weeks. Intervention at 3 weeks post-carcinogen with aerosolized budesonide delayed both hyperplasia and adenoma formation. Once hyperplasia appeared in budesonide treated animals, however, it increased at the same rate as in control animals, indicating a delay in progression. Progression from adenoma to carcinoma was reduced when budesonide was given 12 weeks post-carcinogen. Dietary myo-inositol failed to suppress progression from adenoma to carcinoma when started 12 weeks post-carcinogen. In summary, budesonide is a chemopreventive agent that has inhibitory effects on B[alpha]P induced carcinogenesis of the lung in A/J mice at all stages of progression from hyperplasia formation to cancer.

IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation.

Thymic-dependent differentiation of bone marrow (BM)-derived progenitors and thymic-independent antigen-driven peripheral expansion of mature T cells represent the 2 primary pathways for T-cell regeneration. These pathways are interregulated such that peripheral T-cell expansion is increased in thymectomized versus thymus-bearing hosts after bone marrow transplantation (BMT). This study shows that this interregulation is due to competition between progeny of these 2 pathways because depletion of thymic progeny leads to increased peripheral expansion in thymus-bearing hosts. To test the hypothesis that competition for growth factors modulates the magnitude of antigen-driven peripheral expansion during immune reconstitution in vivo, a variety of T-cell active cytokines were administered after BMT. Of the cytokines (interleukins) tested (IL-3, IL-12, IL-6, IL-2, and IL-7), IL-2 modestly increased peripheral expansion in the face of increasing numbers of thymic emigrants, whereas IL-7 potently accomplished this. This report also demonstrates that the beneficial effect of IL-7 on immune reconstitution is related to both increases in thymopoiesis as well as a direct increase in the magnitude of antigen-driven peripheral expansion. Therefore, the administration of exogenous IL-7, and to a lesser extent IL-2, abrogates the down-regulation in antigen-driven peripheral expansion that occurs in thymus-bearing hosts after BMT. These results suggest that one mechanism by which T-cell-depleted hosts may support antigen-driven T-cell expansion in vivo is via an increased availability of T-cell-active cytokines to support clonal expansion.

The effect of synthetic patch repair of coarctation on regional deformation of the aortic wall.

BACKGROUND: A long-term complication of synthetic patch repair of coarctation is true aneurysm formation. AIM: An in vitro study was undertaken to determine the effects of patch angioplasty on aortic geometry and strain adjacent to the patch. METHODS: Segments of human descending thoracic aorta were subject to 10 pressure loading cycles (10-120 mm Hg; 1.36-16.32 kPa) before and after simulated coarctation repair with a synthetic patch. Local curvature and strain were estimated by fitting a geometric model to reconstructed three-dimensional surface marker points. RESULTS: In the control aortas, when pressure increased from 11 +/- 1.0 to 124 +/- 4.0 mm Hg (1.5 +/- 0.14 to 16.86 +/- 0.54 kPa), average circumferential curvature decreased from 0.1543 +/- 0.03 to 0.1065 +/- 0.03 mm(-1). The average major extension reached a maximum of 1.43 +/- 0.08. After patch implantation, the average circumferential curvature was reduced relative to control at all pressures. Average major extensions were significantly greater than paired control values and reached a maximum of 1.55 +/- 0.08 at 122 +/- 4.0 mm Hg (16.59 +/- 0. 54 kPa). Substantial strain inhomogeneity was observed and major extensions were greatest immediately adjacent to the patch. INFERENCE: Synthetic patch repair of coarctation of the aorta increases wall strain and produces significant regional gradients in strain. With control aortic material properties there may be a substantial increase in wall stress immediately adjacent to the aorta, which could lead to true aneurysm formation.

Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone dipropionate and by the combination of aerosolized budesonide and dietary myo-inositol.

This investigation is part of an effort to develop chemoprevention for carcinogenesis of the lung. It focuses on the efficacy of low doses of synthetic glucocorticoids administered either as single agents or in combination with a second compound, myo-inositol. Glucocorticoids are potent inhibitors of carcinogenesis. The use of low doses is important to avoid potential side-effects. The synthetic glucocorticoid budesonide, administered by aerosol for 20 s three times a week, was studied to determine its effects on benzo[a]pyrene-induced pulmonary adenoma formation in female A/J mice. Two dose levels were employed, 10 and 25 microg/kg body wt. The lower dose produced a 34% reduction in lung tumor formation and the higher dose level a 60% reduction in lung tumors. In additional groups of mice, the effects of 0.3% myo-inositol added to the diet was found to reduce pulmonary tumor formation by 53%. The two agents given in combination resulted in a greater inhibition of lung tumor formation than either by itself. Budesonide at 10 microg/kg body wt plus 0.3% myo-inositol reduced the number of tumors by 60% and budesonide at 25 microg/kg body wt plus 0.3% myo-inositol reduced lung tumor formation by 79%. To determine whether a glucocorticoid other than budesonide would have inhibitory effects in this experimental model, beclomethasone dipropionate administered by aerosol for 20 s three times a week was studied as a single agent and showed almost identical inhibitory properties to budesonide. The doses of the glucocorticoids calculated on a daily basis are within the range of those used widely for control of chronic allergic respiratory diseases in the human. The capacity of low doses of inhaled glucocorticoids to prevent pulmonary neoplasia and the enhancement of this preventive effect by myo-inositol, an essentially non-toxic compound, are findings that should encourage further work to evaluate the applicability of these agents to the prevention of neoplasia of the lung in the human.

Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease.

The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD. These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.

Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure.

OBJECTIVES: This study evaluated the effects of oral therapy with coenzyme Q on echocardiographic and hemodynamic indexes of left ventricular function and on quality of life in patients with chronic left ventricular dysfunction. BACKGROUND: Coenzyme Q is a coenzyme for oxidative phosphorylation and an antioxidant and free radical scavenger. It has been claimed to improve symptoms, quality of life, left ventricular ejection fraction and prognosis in patients with cardiac failure. METHODS: Thirty patients with ischemic or idiopathic dilated cardiomyopathy and chronic left ventricular dysfunction (ejection fraction 26 +/- 6%) were randomized to a double-blind crossover trial of oral coenzyme Q versus placebo, each for 3 months. Right heart pressures, cardiac output and echocardiographic left ventricular volumes were measured at baseline and after each treatment phase, and quality of life was assessed using the Minnesota "Living With Heart Failure" questionnaire. It was calculated that to demonstrate an increase in left ventricular ejection fraction from 25% to 30% with a standard deviation of 5% using 95% confidence intervals with a power of 80% we would require 17 patients. RESULTS: Twenty-seven completed both treatment phases. There was no significant difference in left ventricular ejection fraction, cardiac volumes or hemodynamic and quality of life indices after treatment with coenzyme Q or placebo, although plasma coenzyme Q levels increased from 903 +/- 345 nmol/l(-1) to 2,029 +/- 856 nmol/l(-1). CONCLUSIONS: In patients with left ventricular dysfunction, treatment for three months with oral coenzyme Q failed to improve resting left ventricular systolic function or quality of life despite an increase in plasma levels of coenzyme Q to more than twice basal values.

N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps.

This investigation is part of an effort to develop chemoprevention for carcinogenesis of the large bowel. The agent investigated is N-acetylcysteine (NAC). We used as a predictive biomarker, the proliferative index (PI), in a short-term human study. Patients with previous adenomatous colonic polyps are a cohort with increased risk for colon cancer and an increased PI of colonic crypts. They were randomly assigned to an experimental group given 800 mg/day of NAC for 12 weeks or a placebo group. Using proliferative cell nuclear antigen immunostaining, the PI of colonic crypts was measured prior to and after the treatments. The PI of the NAC group was decreased significantly (P < 0.02) while the placebo group showed no difference (P > 0.45). Since this decrease in PI may be an indicator of decreased risk of colon cancer, more extensive studies of the potential of NAC as a chemopreventive agent for colon cancer appear warranted.

Healthy endings. A collaborative health promotion project for the elderly.

This article describes a collaborative health promotion project between a graduate nursing program at a state university and a small community hospital. The Healthy Endings program provided health promotion education to groups of older adults at a local senior center. Health promotion in this population is vital to prevent complications and decrease risks that affect quality of life. Health promotion programs were designed to be accomplished through three major components: education, health screenings/services, and the referral process. Specific project objectives focused on safety, sensory deprivation, exercise, screening, compliance with medications, and a variety of psychosocial issues. Graduate nursing students functioning proactively in a senior center on a consistent basis were viewed as valuable by both members and staff.

Are you overlooking oral rehydration therapy in childhood diarrhea? It's not just for use in developing countries.

In 1978, Lancet declared that development of effective oral rehydration solutions might prove to be the most important medical advance of the century. Since then, according to estimates of the World Health Organization, use of the solutions has saved a million children a year worldwide. Why, then, has this method of treating diarrhea-induced dehydration been so overlooked in the United States, where several hundred children still die annually of effects of diarrhea? One reason, the authors believe, is that physicians in developed countries have only limited exposure to serious dehydration and so are poorly informed on the principles of intervention. The authors provide practical advice on assessing dehydration in children, providing initial and maintenance rehydration, and reinstituting feeding.

Health care access and utilization among pregnant adolescents.

PURPOSE: To assess access to and use of health care by adolescents prior to their becoming pregnant. METHODS: An interviewer-administered questionnaire was completed by all pregnant adolescents (n = 65) entering the Rochester Adolescent Maternity Program (RAMP) between January and June 1994. Questions addressed access and utilization issues including routine care and other services used, and existence of a regular source of care prior to pregnancy. RESULTS: Sixty-one adolescents (94%) completed questionnaires. Almost all (93%) had made a doctor or clinic visit, and 77% had had a checkup in the prior year. Most had Medicaid (85%) or private insurance (13%). The median number of visits to a regular source of care was 2.0 (range 0-10). Most frequently reported sources of regular care were hospital clinics (43%), community health centers (26%), and private physician offices (15%). Two-thirds (66%) reported having used multiple sources of care. Of those who used other sources in addition to a primary care source, 40% used reproductive health clinics. Adolescents whose primary care source was a traditional physician's office were more likely to also use reproductive health clinics than those who reported using more comprehensive primary care sources. CONCLUSIONS: Most pregnant adolescents in this sample had previously used routine primary care, usually in hospital clinics or health centers. Many of those adolescents also use multiple sources of care, most often for reproductive services. Access to reproductive health services does not seem to have been a problem for these adolescents prior to their pregnancies.

PIP: An interviewer-administered questionnaire was administered to all 65 pregnant adolescents entering the Rochester Adolescent Maternity Program (RAMP) between January and June 1994 as part of a study to measure access to and the use of health care by respondents before they became pregnant. 61 (94%) young women completed the questionnaires. 93% had made a doctor or clinic visit and 77% had had a checkup in the prior year. 85% had Medicaid and 13% had private insurance. The median number of visits to a regular source of care was 2.0 in the range of 0-10. 43% reported receiving regular care from hospital clinics, 26% from community health centers, and 15% from private physician offices. 66% reported having used multiple sources of care. 40% of those who used other sources in addition to a primary care source used reproductive health clinics. Adolescents whose source of primary care was a traditional physician's office were more likely to also use reproductive health clinics than those who reported using more comprehensive primary care sources.

Diastolic ventricular interaction in chronic heart failure.

BACKGROUND: Diastolic ventricular interaction describes a situation in which the volume of one ventricle is directly influenced by the volume of the other ventricle. Such interaction is normally negligible, but it is accentuated in circumstances associated with pulmonary hypertension and volume overload. When this interaction occurs, acute volume unloading results in a reduction in right ventricular end-diastolic volume, as expected, but left ventricular end-diastolic volume paradoxically increases. Since chronic heart failure is a volume-overloaded state associated with pulmonary hypertension, we hypothesised that this interaction may be clinically important in patients with heart failure. METHODS: A radionuclide technique incorporating cardiac scintigraphy was used to measure the effect of acute volume unloading, achieved by 30 mm Hg lower-body suction, on right and left ventricular end-diastolic volumes in 21 patients with chronic heart failure and 12 healthy individuals (controls). FINDINGS: In nine heart-failure patients, there was a paradoxical increase in left ventricular end-diastolic volume in association with an expected decrease in right ventricular end-diastolic volume during lower-body suction. This response was not seen in the control group. The mean change in left ventricular end-diastolic volume differed significantly between the heart-failure patients and controls (6 [SD 19] vs -19 [12] mL, p = 0.0003). However, the change in right ventricular end-diastolic volume was similar in the two groups (-18 [11] vs -20 [8]%. p = 0.70). Patients who increased left ventricular end-diastolic volume during lower-body suction had higher resting pulmonary arterial and pulmonary capillary wedge pressures than the remaining heart-failure patients. INTERPRETATION: The response of nine patients in our study suggests diastolic ventricular interaction, which we believe could be common in patients with chronic heart failure. This finding is relevant to their management, since it emphasises the importance of venodilator therapy. The relation between stroke volume and left ventricular end-diastolic volume, by the Frank-Starting law of the heart, may explain why some patients with chronic heart failure paradoxically increase stroke volume when pulmonary capillary wedge pressure is lowered with vasodilators.

Recombination and the progression of meiosis in Saccharomyces cerevisiae.

Recombination is an essential part of meiosis: in almost all organisms, including Saccharomyces cerevisiae, proper chromosome segregation and the viability of meiotic products is dependent upon normal levels of recombination. In this article we examine the kinetics of the meiotic divisions in four mutants defective in the initiation of recombination. We find that mutations in any of three Early Exchange genes (REC104, REC114 or REC102) confer a phenotype in which the reductional division occurs earlier than in an isogenic wild-type diploid. We also present data confirming previous reports that strains with a mutation in the Early Exchange gene. MEI4 undergo the first division at about the same time as wild-type cells. The rec104 mutation is epistatic to the mei4 mutation for the timing of the first division. These observations suggest a possible relationship between the initiation of recombination and the timing of the reductional division. These data also allow these four Early Exchange genes examined to be distinguished in terms of their role in coordinating recombination with the reductional division.

An analysis of valve re-replacement after aortic valve replacement with biologic devices.

Biologic valve re-replacement was examined in a series of 1343 patients who underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve. A parametric model approach was used to simultaneously model the competing risks of death without re-replacement and re-replacement before death. One hundred eleven patients underwent a first re-replacement for a variety of reasons (69 patients with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and 14 patients with cryopreserved allograft valves). By multivariable analysis younger age at operation was associated with xenograft, 4 degrees C stored allograft, and cryopreserved allograft valve re-replacement. However, this effect was examined in the context of longer survival of younger patients, which increases their exposure to the risk of re-replacement as compared with that in older patients whose decreased survival reduced their probability of requiring valve re-replacement. In patients older than 60 years at the time of aortic valve replacement, the probability of re-replacement (for any reason) before death was similar for xenografts and cryopreserved allograft valves but higher for 4 degrees C stored valves. However, in patients younger than 60 years, the probability of re-replacement at any time during the remainder of the life of the patient was lower with the cryopreserved allograft valve compared with the xenograft valve and 4 degrees C stored allografts.