Dietary protein restriction as a treatment for slowing chronic kidney disease progression: The case against

Low-protein diets (

Double-heater-wire circuits and heat-and-moisture exchangers and the risk of ventilator-associated pneumonia

Objective: To compare the incidence of ventilator-associated pneumonia (VAP) in patients ventilated in intensive care by means of circuits humidified with a hygroscopic heat-and-moisture exchanger with a bacterial viral filter (HME) or hot-water humidification with a heater wire in both inspiratory and expiratory circuit limbs (DHW) or the inspiratory limb only (SHW). Design: A prospective, randomized trial. Setting: A metropolitan teaching hospital's general intensive care unit. Patients: Three hundred eighty-one patients requiring a minimum period of mechanical ventilation of 48 hrs. Interventions: Patients were randomized to humidification with use of an HME (n = 190), SHW (n = 94), or DHW (n = 97). Measurements and Main Results. Study end points were VAP diagnosed on the basis of Clinical Pulmonary Infection Score (CPIS) (1), HME resistance after 24 hrs of use, endotracheal tube resistance, and HME use per patient. VAP occurred with similar frequency in all groups (13%, HME; 14%, DHW; 10%, SHW; p = 0.61) and was predicted only by current smoking (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1-3.9; p =.03) and ventilation days (AOR, 1.05; 95% Cl, 1.0-1.2; p =.001); VAP was less likely for patients with an admission diagnosis of pneumonia (AOR, 0.40; 95% Cl, 0.4-0.2; p =.04). HME resistance after 24 hrs of use measured at a gas flow of 50 L/min was 0.9 cm H2O (0.4-2.9). Endotracheal tube resistance was similar for all three groups (16-19 cm H2O min/L; p =.2), as were suction frequency, secretion thickness, and blood on suctioning (p =.32, p =.06, and p =.34, respectively). The HME use per patient per day was 1.13. Conclusions: Humidification technique does not influence either VAP incidence or secretion characteristics, but HMEs may have air-flow resistance higher than manufacturer specifications after 24 hrs of use.

Quality assurance experience with the randomized neuropathic bone pain trial (Trans-Tasman Radiation Oncology Group, 96.05)

Background and purpose: Trans-Tasman Radiation Oncology Group 96.05 is a prospective randomized controlled trial comparing a single 8 Gy with 20 Gy in five fractions of radiotherapy (RT) for neuropathic pain due to bone metastases. This paper summarizes the quality assurance (QA) activities for the first 234 patients (accrual target 270). Materials and methods: Independent audits to assess compliance with eligibility/exclusion criteria and appropriateness of treatment of the index site were conducted after each cohort of approximately 45 consecutive patients. Reported serious adverse events (SAEs) in the form of cord/cauda equina compression or pathological fracture developing at the index site were investigated and presented in batches to the Independent Data Monitoring Committee. Finally, source data verification of the RT prescription page and treatment records was undertaken for each of the first 234 patients to assess compliance with the protocol. Results: Only one patient was found conclusively not to have genuine neuropathic pain, and there were no detected 'geographical misses' with RT fields. The overall rate of detected infringements for other eligibility criteria over five audits (225 patients) was 8% with a dramatic improvement after the first audit. There has at no stage been a statistically significant difference in SAEs by randomization arm. There was a 22% rate of RT protocol variations involving ten of the 14 contributing centres, although the rate of major dose violations (more than +/- 10% from protocol dose) was only 6% with no statistically significant difference by randomization arm (P = 0.44). Conclusions: QA auditing is an essential but time-consuming component of RT trials, including those assessing palliative endpoints. Our experience confirms that all aspects should commence soon after study activation. Crown Copyright (C) 2003 Published by Elsevier Science Ltd. All rights reserved.

Controlled trial of multidisciplinary care teams for acutely ill medical inpatients: enhanced multidisciplinary care

Background: Acute hospital general medicine services care for ageing complex patients, using the skills of a range of health-care providers. Evidence suggests that comprehensive early assessment and discharge planning may improve efficiency and outcomes of care in older medical patients. Aim: To enhance assessment, communication, care and discharge planning by restructuring consistent, patient-centred multidisciplinary teams in a general medicine service. Methods: Prospective controlled trial enrolling 1538 consecutive medical inpatients. Intervention units with additional allied health staff formed consistent multidisciplinary teams aligned with inpatient admitting units rather than wards; implemented improved communication processes for early information collection and sharing between disciplines; and specified shared explicit discharge goals. Control units continued traditional, referral-based multidisciplinary models with existing staffing levels. Results: Access to allied health services was significantly enhanced. There was a trend to reduced index length of stay in the intervention units (7.3 days vs 7.8 days in control units, P = 0.18), with no change in 6-month readmissions. in-hospital mortality was reduced from 6.4 to 3.9% (P = 0.03); less patients experienced functional decline in hospital (P = 0.04) and patients' ratings of health status improved (P = 0.02). Additional staffing costs were balanced by potential bed-day savings. Conclusion: This model of enhanced multidisciplinary inpatient care has provided sustainable efficiency gains for the hospital and improved patient outcomes.

A randomised trial of home vs hospital intravenous antibiotic therapy in adults with infectious diseases

Objective. Despite widespread adoption of home care services, few randomised trials have compared health outcomes in the hospital and at home. We report a prospective, randomised trial of home versus hospital therapy in adults receiving intravenous (IV) antibiotics. Our objective was to show that home care is a feasible alternative to hospitalisation over a broad range of infections, without compromise to quality of life (QOL) or clinical outcomes. Methods. Consenting adults requiring IV antibiotics were randomised to complete therapy at home or in hospital. Short Form 36 and Perceived Health Competence Scale (PHCS) were used for assessment of QOL. Statistical analysis used unpaired t-tests, Mann-Whitney tests and ANOVA. Results. One hundred and twenty-nine admissions were referred. Recruitment was hampered by patient preference for one therapy over another. 82 (62%) were included and randomised: 44 to home, 38 to hospital; the two groups had comparable characteristics. There were no differences in improvements in QOL and PHCS scores between the two groups after treatment. Treatment duration was median 11.5 days (range 3 - 57) and 11 days (range 4 - 126) for home and hospital groups, respectively. Home therapy costs, approximately, half that of hospital therapy. Time to readmission was longer after hospital therapy. Conclusion. Out study showed that home IV therapy is welt tolerated, is less costly, is not associated with any major disadvantage to QOL or clinical outcomes compared to hospital therapy, and is an appropriate treatment option for selected patients. (C) 2003 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Effectiveness and safety of repeat courses of hylan G-F 20 in patients with knee osteoarthritis

Objective: To compare the effectiveness and safety of repeat treatment with hylan G-F 20 based on data from a randomized, controlled trial [Raynauld JP, Torrance GW, Band PA, Goldsmith CH, Tugwell P, Walker V, et al. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results. Osteoarthritis Cartilage 2002;10:506-17]. The hypotheses tested were whether the single-course and repeat-course subgroups would be superior to appropriate care and not different from each other. Method: A total of 255 patients with knee osteoarthritis were randomized to appropriate care with hylan G-F 20 or appropriate care without hylan G-F 20. The hylan G-F 20 group was partitioned into two subgroups: (1) patients who received a single course of hylan G-F 20; and (2) patients who received two or more courses of hylan G-F 20. Results: For the primary effectiveness measure, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score as a percent of baseline, the single-course subgroup improved by 41%, the repeat-course subgroup by 35%, and the appropriate care group by 14%. Both subgroups improved significantly more than the appropriate care group (P < 0.05), and were not statistically significantly different from each other (70% power to detect a 20% difference). Secondary effectiveness measures showed similar results. In the repeat-course subgroup, no statistically significant differences were found in the number of local adverse events, the number of patients with local adverse events, or arthrocentesis rates between the first and repeat courses of treatment. Conclusions: Although the study was neither designed nor powered to examine repeat treatment, this a posteriori analysis provides support for a favorable effectiveness and safety profile of hylan G-F 20 in repeat course patients. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Carvedilol reduces the costs of medical care in severe heart failure: An economic analysis of the COPERNICUS study applied to the United Kingdom

Background: The aim of this study was to determine the effects of carvedilol on the costs related to the treatment of severe chronic heart failure (CHF). Methods: Costs for the treatment for heart failure within the National Health Service (NHS) in the United Kingdom (UK) were applied to resource utilisation data prospectively collected in all patients randomized into the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Unit-specific, per them (hospital bed day) costs were used to calculate expenditures due to hospitalizations. We also included costs of carvedilol treatment, general practitioner surgery/office visits, hospital out-patient clinic visits and nursing home care based on estimates derived from validated patterns of clinical practice in the UK. Results: The estimated cost of carvedilol therapy and related ambulatory care for the 1156 patients assigned to active treatment was 530,771 pound (44.89 pound per patient/month of follow-up). However, patients assigned to carvedilol were hospitalised less often and accumulated fewer and less expensive days of admission. Consequently, the total estimated cost of hospital care was 3.49 pound million in the carvedilol group compared with 4.24 pound million for the 1133 patients in the placebo arm. The cost of post-discharge care was also less in the carvedilol than in the placebo group (479,200 pound vs. 548,300) pound. Overall, the cost per patient treated in the carvedilol group was 3948 pound compared to 4279 pound in the placebo group. This equated to a cost of 385.98 pound vs. 434.18 pound, respectively, per patient/month of follow-up: an 11.1% reduction in health care costs in favour of carvedilol. Conclusions: These findings suggest that not only can carvedilol treatment increase survival and reduce hospital admissions in patients with severe CHF but that it can also cut costs in the process.

Multi-centre Phase II trial of the polyamine synthesis inhibitor SAM486A (CGP48664) in patients with metastatic melanoma

Purpose: To determine the activity and tolerability of SAM496A, an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), in patients with metastatic melanoma who had not received prior chemotherapy. Selected patients were offered participation in two sub-studies examining early changes in tumor metabolism with FDG-PET and changes in tumor polyamine content. Patients and methods: Fifteen patients with measurable metastatic melanoma, normal cardiac function, and no known CNS metastases were eligible and received SAM486A by 1-hour IV infusion daily for 5 days every 3 weeks. Response was assessed by SWOG criteria. Results: No patient had a confirmed partial response. Fatigue/lethargy, myalgia and neutropenia were the main toxicities but no febrile neutropenia or grade 4 non-hematological toxicity occurred. Five patients had PET scans pre-treatment and on days 8-12 of cycle 1. No patient had reduction of tumor metabolism. Serial biopsy in one patient showed alterations in polyamines consistent with SAMDC inhibition. Conclusions: Using the present dose and schedule of administration, SAM486A does not have significant therapeutic potential in patients with metastatic melanoma.

Recombinant human activated protein C improves pulmonary function in ovine acute lung injury resulting from smoke inhalation and sepsis

Objective: To investigate the effects of recombinant human activated protein C (rhAPC) on pulmonary function in acute lung injury (ALI) resulting from smoke inhalation in association with a bacterial challenge. Design: Prospective, randomized, controlled, experimental animal study with repeated measurements. Setting: Investigational intensive care unit at a university hospital. Subjects: Eighteen sheep (37.2 +/- 1.0 kg) were operatively prepared and randomly allocated to either the sham, control, or rhAPC group (n = 6 each). After a tracheotomy had been performed, ALI was produced in the control and rhAPC group by insufflation of 4 sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live Pseudomonas aeruginosa bacteria (containing 2-5 x 10(11) colony forming units) was instilled into the lungs according to an established protocol. The sham group received only the vehicle, i.e., 4 sets of 12 breaths of room air and instillation of 30 mL normal saline. The sheep were studied in the awake state for 24 hrs and were ventilated with 100% oxygen. RhAPC (24 mu g/kg/hr) was intravenously administered. The infusion was initiated 1 hr post-injury and lasted until the end of the experiment. The animals were resuscitated with Ringer's lactate solution to maintain constant pulmonary artery occlusion pressure. Measurements and Main Results., In comparison with nontreatment in controls, the infusion of rhAPC significantly attenuated the fall in PaO2/FiO(2) ratio (control group values were 521 +/- 22 at baseline [BL], 72 +/- 5 at 12 hrs, and 74 +/- 7 at 24 hrs, vs. rhAPC group values of 541 +/- 12 at BL, 151 +/- 29 at 12 hours [p < .05 vs. control], and 118 +/- 20 at 24 hrs), and significantly reduced the increase in pulmonary microvascular shunt fraction (Qs/Qt; control group at BL, 0.14 +/- 0.02, and at 24 hrs, 0.65 +/- 0.08; rhAPC group at BL, 0.24 +/- 0.04, and at 24 hrs, 0.45 +/- 0.02 [p < .05 vs. control]) and the increase in peak airway pressure (mbar; control group at BL, 20 +/- 1, and at 24 hrs, 36 +/- 4; rhAPC group at BL, 21 +/- 1, and at 24 hrs, 28 +/- 2 [p < .05 vs. control]). In addition, rhAPC limited the increase in lung 3-nitrotyrosine (after 24 hrs [%]: sham, 7 +/- 2; control, 17 +/- 1; rhAPC, 12 +/- 1 [p < .05 vs. control]), a reliable indicator of tissue injury. However, rhAPC failed to prevent lung edema formation. RhAPC-treated sheep showed no difference in activated clotting time or platelet count but exhibited less fibrin degradation products (1/6 animals) than did controls (4/6 animals). Conclusions. Recombinant human activated protein C attenuated ALI after smoke inhalation and bacterial challenge in sheep, without bleeding complications.

Long-term increase in sunscreen use in an Australian community after a skin cancer prevention trial

Background. Given the public health burden of skin cancer in white populations, an increase in sun protective behavior is needed. In a highrisk community, we assessed long-term Sunscreen use among people who had participated in a randomized trial of daily Sunscreen application for prevention of skin cancer. Methods. In 1992, 1621 residents of the subtropical Australian township of Nambour were randomly allocated to either daily or discretionary sunscreen use until 1996. From 1997 to 2002, we monitored by questionnaires their ongoing sunscreen use. Results. People who had never or irregularly used sunscreen when in summer sun before the trial were more likely (P < 0.0001) to be sustaining regular application especially to their face (20% vs. 11%) and forearms (14% vs. 5%) if they had been allocated to daily, not discretionary, use of sunscreen for 5 years. Conclusions. Regular voluntary sunscreen use for skin cancer prevention can be sustained by sun-sensitive people in the long term. Habit formation appears to be an important goal for sun protection programs among those living, or on vacation, in sunny places. (c) 2005 Elsevier Inc. All rights reserved.

The treatment of pterygium

The treatment of pterygium is still quite controversial, with various treatments being advocated in the scientific literature. Unfortunately, there are very few well-conducted controlled clinical trials of treatments. However, years of anecdotal and noncontrolled studies have confirmed that some methods, such as bare scleral closure, are no longer acceptable in the treatment of pterygium and that other methods are likely to be more useful. In the future it will be important to develop a grading system, and surgeons will need to be conservative in the treatment of pterygium until such time as a single treatment provides a lower recurrence rate and complication rate.

Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer

Purpose: To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer. Methods: Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals. Results: All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible. Conclusion: Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience. If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and/or survival, then patients would view these therapeutic gains as worthwhile. Compliance with short-term goserelin was excellent, confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment. However, for more protracted androgen deprivation, survival advantages and deleterious effects need to be assessed in parallel, in order to determine the optimal duration of treatment. (C) 2003 Elsevier Ireland Ltd. All fights reserved.

Optimising exercise training in peripheral arterial disease

Peripheral arterial disease (PAD) is an obstructive condition where the flow of blood through peripheral arteries is impeded. During periods of increased oxygen demand (e.g. during exercise), peripheral limb ischaemia occurs, resulting in the sensation of muscle pain termed 'claudication'. As a result of claudication, subjects' ability to exercise is greatly reduced affecting their quality of life. Although many treatment options for patients with PAD exist, exercise training is an effective and low-cost means of improving functional ability and quality of life. Currently, there are limited specific recommendations to assist the exercise prescription and programming of these individuals. This review summarises data from 28 exercise training studies conducted in patients with PAD and formulates recommendations based on their results. Exercise training for patients with PAD should involve three training sessions per week comprising 45 minutes of intermittent treadmill walking in a supervised environment for a time period of 20 weeks or more. Encouragement and direction is given to further research aimed at investigating the effectiveness of training programmes in these patients.

The relative importance of vascular structure and function in predicting cardiovascular events

OBJECTIVES We sought to assess the prognostic utility of brachial artery reactivity (BAR) in patients at risk of cardiovascular events. BACKGROUND Impaired flow-mediated vasodilation measured by BAR is a marker of endothelial dysfunction. Brachial artery reactivity is influenced by risk factors and is responsive to various pharmacological and other treatments. However, its prognostic importance is uncertain, especially relative to other predictors of outcome. METHODS A total of 444 patients were prospectively enrolled to undergo BAR and follow-up. These patients were at risk of cardiovascular events, based on the presence of risk factors or known or suspected cardiovascular disease. We took a full clinical history, performed BAR, and obtained carotid intima-media thickness (IMT) and left ventricular mass and ejection fraction. Patients were followed up for cardiovascular events and all-cause mortality. Multivariate Cox regression analysis was performed to assess the independent association of investigation variables on outcomes. RESULTS The patients exhibited abnormal BAR (5.2 +/- 6.1% [mean +/- SD]) but showed normal nitrate-mediated dilation (9.9 +/- 7.2%) and normal mean IMT (0.67 +/- 0.12 mm [average]). Forty-nine deaths occurred over the median follow-up period of 24 months (interquartile range 10 to 34). Patients in the lowest tertile group of BAR (<2%) had significantly more events than those in the combined group of highest and mid-tertiles (p = 0.029, log-rank test). However, mean IMT (rather than flow-mediated dilation) was the vascular factor independently associated with mortality, even in the subgroup (n = 271) with no coronary artery disease and low risk. CONCLUSIONS Brachial artery reactivity is lower in patients with events, but is not an independent predictor of cardiovascular outcomes in this cohort of patients. (C) 2004 by the American College of Cardiology Foundation.