Intra-operative blood salvage in total hip and knee arthroplasty.

PURPOSE: To review records of 371 patients who underwent total hip or knee arthroplasty (THA or TKA) with intra-operative blood salvage to determine the allogeneic blood transfusion rate and the predictors for allogeneic blood transfusion. METHODS: Records of 155 male and 216 female consecutive patients aged 17 to 95 (mean, 70) years who underwent primary THA or TKA by a single surgeon with the use of intra-operative blood salvage were reviewed. RESULTS: The preoperative haemoglobin level was <120 g/dl in 15% of THA patients and 5% of TKA patients; the allogeneic transfusion rate was 24% in THA patients and 12% in TKA patients. Despite routine use of intra-operative blood salvage, only 59% of THA patients and 63% of TKA patients actually received salvaged blood, as a minimum of 200 ml blood loss was required to activate blood salvage. In multivariable analysis, predictors for allogeneic blood transfusion were female gender (adjusted odds ratio [OR]=2.8, p=0.02), age >75 years (adjusted OR=5.9, p<0.001), and preoperative haemoglobin level <120 g/l (adjusted OR=30.1, p<0.001), despite the use of intra-operative blood salvage. Patients who received allogeneic blood transfusion had a longer hospital stay and greater complication rate. CONCLUSION: Intra-operative blood salvage is not effective in preventing allogeneic blood transfusion in patients with a preoperative haemoglobin level <120 g/l. It should be combined with preoperative optimisation of the haemoglobin level or use of tranexamic acid.

Does the presence of sensory hypersensitivity influence outcomes of physical rehabilitation for chronic whiplash?--A preliminary RCT.

Patients with chronic whiplash associated disorders present with varied sensory, motor and psychological features. In this first instance it was questioned whether a multimodal program of physical therapies was an appropriate management to be broadly prescribed for these patients when it was known that some would have sensory features suggestive of a notable pain syndrome. A randomised controlled trial was conducted with 71 participants with persistent neck pain following a motor vehicle crash to explore this question. Participants were randomly allocated to receive either a multimodal physiotherapy program (MPT) or a self-management program (SMP) (advice and exercise). In the randomisation process, participants were stratified according to the presence or not of widespread mechanical or cold hyperalgesia. The intervention period was 10 weeks and outcomes were assessed immediately following treatment. Even with the presence of sensory hypersensitivity in 72.5% of subjects, both groups reported some relief of neck pain and disability (Neck Disability Index) and it was superior in the group receiving multimodal physiotherapy (p=0.04). Post-hoc observations however suggested that relief was marginal in the subgroup with both widespread mechanical and cold hyperalgesia. Further research is required to test the validity of this sub-group observation and to test the effect of the intervention in the long term.

A systematic review and meta-analysis of clinical trials on physical interventions for lateral epicondylalgia.

A systematic review of the literature on the effectiveness of physical interventions for lateral epicondylalgia (tennis elbow) was carried out. Seventy six randomised controlled trials were identified, 28 of which satisfied the minimum criteria for meta-analysis. The evidence suggests that extracorporeal shock wave therapy is not beneficial in the treatment of tennis elbow. There is a lack of evidence for the long term benefit of physical interventions in general. However, further research with long term follow up into manipulation and exercise as treatments is indicated.

Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia.

Between 1993 and 2001, 106 patients with esophageal cancer were reviewed at a multidisciplinary clinic and treated with palliative intent by chemoradiation therapy. This study assesses the palliative benefit on dysphagia and documents the toxicity of this treatment. The study population comprised 72 men and 34 women with a median age of 69 years. Patients were treated with a median radiation dose of 35 Gy in 15 fractions with a concurrent single course of 5 FU-based chemotherapy. Dysphagia was measured at the beginning and completion of treatment and at monthly intervals until death, using a modified DeMeester (4-point) score. Treatment was well tolerated, with only 5% of patients failing to complete therapy. The treatment-related mortality was 6%. The median survival for the study population was 7 months. The median baseline score at presentation was 2 (difficulty with soft food). Following treatment, 49% of patients were assessed as having a dysphagia score of 0 (no dysphagia). Seventy-eight per cent had an improvement of at least one grade in their dysphagia score after treatment. Only 14% of patients showed no improvement with treatment. Fifty-one per cent maintained improved swallowing until the time of last follow-up or death. This single-institution study shows that chemoradiation therapy administered for the palliation of malignant dysphagia is well tolerated and produces a sustainable normalization in swallowing for almost half of all patients.

Skin exposure during conventional phototherapy in preterm infants: A randomized controlled trial.

OBJECTIVE: To assess the effect of reduced skin exposure in preterm infants receiving overhead phototherapy treatment on total serum bilirubin (TSB). METHODS: Randomized controlled trial. Preterm infants (>1500 g birthweight and < or = 36 weeks gestation) were randomized to being nursed either partially clothed with only disposable nappies and in posturally supported positions (n = 30) or naked without postural support (n = 29). Primary outcome was mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment (irradiance of 6 microW cm(-2)/nm at a wavelength of 425-475 nm). The incidence of rebound jaundice, number of infants continuing to receive phototherapy treatment at 24 h periods, parental stress, mother-infant interaction and mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment were examined. RESULTS: Mean TSB percentage change at 24 h of completed treatment for the partially clothed group was 15.4% (+/-18) and for the naked group 19% (+/-15) (mean difference 3.6% 95% CI -5.1, 12.3). No other outcomes were significantly affected by reduced skin exposure to overhead phototherapy treatment. CONCLUSION: Our results show no statistically significant difference in TSB level change using either nursing practice.

Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study.

BACKGROUND: Pulmonary hypertensive crises (PHTC) are a major cause of morbidity and mortality after congenital heart surgery. Inhaled nitric oxide is frequently used as rescue therapy. We did a randomised double-blind study to investigate the role of routinely administered inhaled nitric oxide to prevent pulmonary hypertension in infants at high risk. METHODS: We enrolled 124 infants (64 male, 60 female; median age 3 months [IQR 1-5]), 76% with large ventricular or atrioventricular septal defects, who had high pulmonary flow, pressure, or both, and were undergoing corrective surgery for congenital heart disease. They were randomly assigned continuous low-dose inhaled nitric oxide (n=63) or placebo (n=61) from surgery until just before extubation. We measured the numbers of PHTC, time on study gas, and hours spent in intensive care. Analysis was done by intention to treat. FINDINGS: Compared with placebo, infants receiving inhaled nitric oxide had fewer PHTC (median four [IQR 0-12] vs seven [1-19]; relative risk, unadjusted 0.66, p<0.001, adjusted for dispersion 0.65, p=0.045) and shorter times until criteria for extubation were met (80 [38-121] vs 112 h [63-164], p=0.019). Time taken to wean infants off study gas was 35% longer in the nitric oxide group than in the placebo group (p=0.19), but the total time on the study gas was still 30 h shorter for the nitric oxide group (87 [43-125] vs 117 h [67-168], p=0.023). No important toxic effects arose. INTERPRETATION: In infants at high risk of pulmonary hypertension, routine use of inhaled nitric oxide after congenital heart surgery can lessen the risk of pulmonary hypertensive crises and shorten the postoperative course, with no toxic effects.

A cohort study of hormone replacement therapy given to women previously treated for breast cancer.

UNLABELLED: Women who have been previously treated for breast cancer are usually advised to avoid hormone therapy for fear of increasing their risk of tumor recurrence. However, for some women, menopausal symptoms are so severe that their quality of life is poor. Because ethic committees are reticent to permit a double-blind randomized trial, we performed a cohort study of hormone therapy after breast cancer. METHODS: The study group comprised 1472 women with breast cancer. A total of 167 subjects had used an oral or transdermal estrogen after their treatment for breast cancer. Amongst these estrogen users, 152 (91%) had also used a progestin. In total, 106 other women had used a progestin alone as a treatment for menopausal flushes and not as a treatment for breast cancer. Cox regression analysis was performed using estrogen as a time-dependent covariate with disease-free interval as the outcome. RESULTS: The uncorrected hazard ratio for the estrogen-progestin users was 0.67 (95% confidence interval (CI) 0.38-1.16) and for the progestin alone users was 0.85 (95% CI 0.44-1.65). CONCLUSIONS: This study was unable to demonstrate a significant increase in risk of breast cancer recurrence for women who used HRT and suggests that the time is now appropriate for a randomized prospective trial of hormone therapy after breast cancer.

Hemorrhagic complications of intravenous heparin use.

To document the incidence of bleeding complications occurring in patients admitted to a cardiology service treated with intravenous heparin and to identify the major risk factors for these adverse events. Intravenous heparin is effective treatment for a variety of cardiologic conditions but is associated with a number of adverse effects, including hemorrhage. During the study, 1,253 consecutive patients were admitted for acute cardiac care and of these, 416 were treated with intravenous heparin. A total of 39 complications occurred in 37 heparin-treated patients (8.9%), of which 23 were hemorrhagic complications occurring in 21 heparin-treated patients (5.5%). Of these hemorrhagic complications, 12 were directly related to a vascular access site and 11 were apparently "spontaneous" hemorrhages. There was no apparent relation between the dose (mean 1,021 U/hour [range 531 to 1,882]) or duration (6.7 +/- 5.7 days) of heparin therapy and hemorrhagic complications. In a multivariate analysis, female gender (odds ratio [OR] 4.76 [14.39 to 1.56]; p = 0.006), recent thrombolytic therapy (OR 12.9 [4.1 to 40.6]; p <0.0001), and a reduced admission hemoglobin (OR 1.41 [0.52 to 0.97]; p = 0.031) were significantly predictive of a hemorrhagic event. The incidence of cardiac catheterization procedures was not significantly higher in the complication group (OR 3.9 [0.84 to 18.4]; p = 0.082). Aspirin therapy, admission platelet count, and weight were noncontributory. Hemorrhagic complications occurred in 5.5% of patients receiving a continuous infusion of heparin. The use of thrombolytic therapy, female gender (independent of weight), and a reduced admission hemoglobin were significant independent predictors of hemorrhagic events.

Improved quality of life with megestrol acetate in patients with endocrine-insensitive advanced cancer: a randomised placebo-controlled trial. Australasian Megestrol Acetate Cooperative Study Group.

PURPOSE: To investigate the effect of two doses of megestrol acetate (MA) compared with placebo on quality of life (QoL) and nutritional status (NS) in patients with advanced endocrine-insensitive cancer. PATIENTS AND METHODS: Two hundred forty patients were randomised to double-blind MA 480 mg/day, MA 160 mg/day, or matching placebo for 12 weeks. Nutritional status (including weight, skinfold thickness and midarm circumference) and QoL (using 6 linear analogue self-assessment (LASA) scales) were assessed at randomisation and after four, eight and 12 weeks. A QoL ranking incorporating QoL and death was also used ranging from 1 = dead to 5 = much better QoL. RESULTS: One hundred seventy-four patients were assessable at week four, 136 at week eight and 103 patients at week 12. Patients receiving MA reported substantially better appetite (P = 0.001), mood (P = 0.001) and overall quality of life (P < 0.001), and possibly less nausea and vomiting (P = 0.08) than patients receiving placebo, based on a test for trend. A larger benefit was seen with the higher dose which (unlike the lower dose) was significantly better in pairwise comparisons with placebo for appetite, mood and overall QoL (each P < or = 0.001). Despite some missing data on QoL scores, QoL ranking was available on 227 (95%) of patients with significantly higher QoL ranking associated with MA (P = 0.002). Improvements in QoL occurred early within four weeks and were sustained. No statistically significant differences were observed in NS measurements, including weight (P = 0.29). Side effects of therapy were minor and did not differ significantly across treatments. CONCLUSION: Megestrol acetate given at 480 mg/day is useful palliation in patients with endocrine-insensitive advanced cancer. It improves appetite, mood and overall quality of life in these patients, although not through a direct effect on nutritional status.

A syndrome of hypotonia, psychomotor retardation, seizures, delayed and dysharmonic skeletal maturation, and congenital fibre type disproportion.

Three unrelated Puerto Rican boys, ranging in age from 3 to 4 years, had marked, central, non-progressive hypotonia, chronic constipation, severe psychomotor retardation, seizures or abnormal electroencephalograph or both, abnormal dermatoglyphics, delayed bone age, dysharmonic skeletal maturation, and preponderance and larger size of type 2 muscle fibres. Additional findings included narrow, high arched palate, prominent nasal root, long philtrum, distended abdomen, and drooling from open mouth. Two of the three patients also had undescended testes, hypertelorism, and tapered fingers. Birth weight, postnatal physical growth, and head size were average. Family and gestational histories and laboratory evaluations were normal. The combination of features observed in the three boys appears to be distinct and to represent a new syndrome.

Dynamic balanced randomization for clinical trials.

Common methods of treatment allocation for multi-centre and/or stratified randomized clinical trials can result in substantial differences between the number of patients allocated to each treatment arm. This can occur in the overall trial for a permuted block design or within individual institutions/strata when using a minimization scheme. This may lead to a bias in the result. Also, these procedures can be predictable, with the possibility of an investigator-introduced selection bias. An easily implemented method of randomization is proposed which attempts to overcome these problems by balancing treatment allocations both within strata and across the trial as a whole. The method keeps a running tally on total treatment allocation numbers at all stratification levels. When a patient accrues a hierarchical decision rule is applied, and the allocation is deterministic if certain pre-defined limits are exceeded, and random otherwise. The method is an extension of the big stick design of Soares and Wu, and is related to both Zelen's key number randomization methods and the schemes of Nordle and Brantmark. Simulation studies are used to demonstrate that major imbalances possible with other schemes do not occur using this method, and that the potential for selection bias is much reduced.

The cycling of combination antirheumatic drug therapy in rheumatoid arthritis.

In this open pilot study a combination of hydroxychloroquine, prednisolone and alternating months of treatment with sulphasalazine or oral weekly pulse methotrexate has been investigated in 16 patients with rheumatoid arthritis (RA) refractory to a total of 67 disease suppressive medications. Results at 3 months indicated significant improvements in visual analogue score for pain, joint count, Ritchie index, scale of disability related to activities of daily living, ESR, rheumatoid factor and C-reactive protein. This degree of improvement, however, was not maintained 6 and 12 months after commencement of treatment. Pain score, Ritchie index and ESR were the only parameters demonstrating significant improvement at 12 months. Therapy was terminated in eight patients, half due to lack of efficacy and half because of side effects.

Correlation between tests of muscle involvement and clinical muscle weakness in polymyositis and dermatomyositis.

A correlation study was performed on the degree of muscle weakness in 36 patients with dermatomyositis and 69 with polymyositis in relation to muscle biopsy findings, electromyography (EMG) abnormalities, and serum concentrations of creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes. Statistically significant correlations were found between muscle weakness and EMG results in patients with polymyositis, and between muscle weakness and serum CK and AST levels in dermatomyositis. As expected, correlations were found between the results of the three enzyme determinations in both groups of patients.

Comparative controlled trial of low-dose weekly methotrexate versus azathioprine in rheumatoid arthritis: 3-year prospective study.

Fifty-three patients with rheumatoid arthritis who required immunosuppressive therapy were commenced in a randomized trial comparing azathioprine to weekly oral pulse methotrexate. After an initial 24-week period, both groups had significantly improved from baseline measures of pain and functional capacity and there were no significant differences in clinical outcomes between the two groups. Laboratory variables of disease activity showed a significant improvement in haemoglobin and ESR in the methotrexate group. Subsequently, the patients were followed for up to 3 years. After one year, more than half of the patients in both groups had discontinued therapy due to inefficacy or adverse events. Adverse effects were more frequent in the patients treated with methotrexate, but withdrawal rates were similar in both groups. From these data, the probability of a patient continuing therapy with either agent for greater than 18 months is low.

Infra-red surface thermography. Evaluation of a new radiometry instrument for measuring skin temperature over joints.

A study is reported of the evaluation of a new portable, light-weight, infrared thermometer, for the measurement of the skin temperature over joints. A high degree of reproducibility was observed, but no increase in heat was found over selected rheumatoid joints. The instrument will prove useful in detecting temperature changes in disease states where the changes are considerable, and where the ambient temperature can be strictly controlled.