Nora Donaldson

Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study

BACKGROUNDnAlthough the Kings College Hospital (KCH) selection criteria for emergency liver transplantation in paracetamol-induced acute liver failure are widely used, strategies to improve sensitivity and facilitate earlier transplantation are required. We investigated the use of arterial blood lactate measurement for the identification of transplantation candidates.nnnMETHODSnIn a single-centre study, we measured arterial blood lactate early (median 4 h) and after fluid resuscitation (median 12 h) in patients admitted to a tertiary-referral intensive-care unit. Threshold values that best identified individuals likely to die without transplantation were derived in a retrospective initial sample of 103 patients with paracetamol-induced acute liver failure and applied to a prospective validation sample of 107 patients. Predictive value and speed of identification were compared with those of KCH criteria.nnnFINDINGSnIn the initial sample, median lactate was significantly higher in non-surviving patients than in survivors both in the early samples (8.5 [range 1.7--21.0] vs 1.4 [0.53--7.9] mmol/L, p<0.0001) and after fluid resuscitation (5.5 [1.3--18.6] vs 1.3 [0.26--3.2], p<0.0001). Applied to the validation sample, a threshold value of 3.5 mmol/L early after admission had sensitivity 67%, specificity 95%, positive likelihood ratio 13, and negative likelihood ratio 0.35; the corresponding values for a threshold of 3.0 mmol/L after fluid resuscitation were 76%, 97%, 30, and 0.24. Combined early and postresuscitation lactate concentrations had similar predictive ability to KCH criteria but identified non-surviving patients earlier (4 [3--13] vs 10 [3.5--19.5] h, p=0.01). Addition of postresuscitation lactate concentration to KCH criteria increased sensitivity from 76% to 91% and lowered negative likelihood ratio from 0.25 to 0.10.nnnINTERPRETATIONnArterial blood lactate measurement rapidly and accurately identifies patients who will die from paracetamol-induced acute liver failure. Its use could improve the speed and accuracy of selection of appropriate candidates for transplantation.

Alternative strategies for stroke care: a prospective randomised controlled trial

BACKGROUNDnOrganised specialist care for stroke improves outcome, but the merits of different methods of organisation are in doubt. This study compares the efficacy of stroke unit with stroke team or domiciliary care.nnnMETHODSnA single-blind, randomised, controlled trial was undertaken in 457 acute-stroke patients (average age 76 years, 48% women) randomly assigned to stroke unit, general wards with stroke team support, or domiciliary stroke care, within 72 h of stroke onset. Outcome was assessed at 3, 6, and 12 months. The primary outcome measure was death or institutionalisation at 12 months. Analyses were by intention to treat.nnnFINDINGSn152 patients were allocated to the stroke unit, 152 to stroke team, and 153 to domiciliary stroke care. 51 (34%) patients in the domiciliary group were admitted to hospital after randomisation. Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team (21/152 [14%] vs 45/149 [30%]; p<0.001) or domiciliary care (21/152 [14%] vs 34/144 [24%]; p=0.03), mainly as a result of reduction in mortality. The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team (129/152 [85%] vs 99/149 [66%]; p<0.001) or domiciliary care (129/152 [85%] vs 102/144 [71%]; p=0.002). These differences were present at 3 and 6 months after stroke.nnnINTERPRETATIONnStroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality, institutionalisation, and dependence after stroke.

A Randomized Controlled Trial of an Enhanced Balance Training Program to Improve Mobility and Reduce Falls in Elderly Patients

OBJECTIVES: To evaluate the effectiveness of an enhanced balance training program in improving mobility and well‐being of elderly people with balance problems.

Can differences in management processes explain different outcomes between stroke unit and stroke-team care?

BACKGROUNDnStroke units reduce mortality and dependence, but the reasons are unclear. We have compared differences in management and complications of patients with acute stroke who were admitted to a stroke unit or to a general ward as part of a previously reported randomised trial.nnnMETHODSn304 patients had been randomly assigned to stroke units (n=152) or to general wards supported by a specialist stroke team (152). We used a structured format to gather prospective data on the frequency of prespecified interventions in each of the major aspects of stroke care. Observations were undertaken daily for the first week and every week for the next 3 months by independent observers. The effect of differences in management on outcome at 3 months was assessed with the modified Rankin score, dichotomised to good (0-3) and poor (4-6) outcome.nnnFINDINGSnPatients in the stroke unit were monitored more frequently (odds ratio 2.1 [1.3-3.4]) and more patients received oxygen (2.0 [1.3-3.2]), antipyretics (6.4 [1.5-27.5]), measures to reduce aspiration (6.0 [2.3-15.5]), and early nutrition (14.4 [5.1-40.9]) than those in general wards. Complications were less frequent in patients in the stroke unit than those in general wards (0.6 [0.2-0.7]), with fewer patients having progression of stroke, chest infection, or dehydration. Measures to prevent aspiration, early feeding, stroke unit management, and frequency of complications independently affected outcome.nnnINTERPRETATIONnDifferences in management and complications between the stroke unit and general wards differ substantially, even when specialist support is provided. Such differences could be responsible for the more favourable outcome seen in patients on stroke units than those on general wards.

Fecal M2-Pyruvate Kinase (M2-PK): A Novel Marker of Intestinal Inflammation

Background: Surrogate markers of bowel inflammation are increasingly being recognized as important, not only as markers of disease activity in inflammatory bowel disease (IBD) but also to differentiate irritable bowel syndrome (IBS) from IBD. The dimeric M2‐isoform of pyruvate kinase (M2‐PK) has been reported to be elevated in fecal specimens from colorectal cancer (CA) patients, but its role in IBD is unknown. This study investigated the usefulness of fecal M2‐PK in cohorts of patients with IBD, IBS, and CA. Methods: Stool samples were obtained for calprotectin and M2‐PK measurements in patients with previously diagnosed IBD or new patients being investigated for lower gastrointestinal (GI) symptoms in a UK university hospital. Other investigations were performed as directed by the investigating physician and patients with known IBD were assessed for disease activity by a physician global assessment, Harvey–Bradshaw index (HBI), or endoscopic grading. Results: Fecal M2‐PK and calprotectin measurements were obtained for 148 patients: 50 with ulcerative colitis (UC); 31 with Crohns disease (CD), 43 with irritable bowel syndrome/functional bowel disorders (IBS); 7 with colorectal CA, and 17 with miscellaneous conditions (excluded from the analysis). Median M2‐PK values (U/mL) were significantly elevated in UC: 20.0 (95% confidence interval [CI] 5.4–69.0, P < 0.0001), CD: 24.3 (95% CI 6.4–44.0, P < 0.0001), and CA: 7.0 (95% CI 4.3–88.0, P < 0.0006) compared to IBS: 0.1 (95% CI 0.0–3.2). There was a strong linear correlation of M2‐PK with calprotectin levels. A predetermined cutoff level of 3.7 U/mL for a normal M2‐PK test produced a sensitivity, specificity, and positive predictive value (PPV) of 73%, 74%, and 89%, respectively, for organic disease. Furthermore, M2‐PK levels were significantly elevated in active, compared to inactive, disease for CD (30 versus 0.55 U/mL, P < 0.005) and UC (40 versus 1.2 U/mL, P = 0.006), respectively. Conclusions: Fecal M2‐PK is elevated in IBD as well as in CA patients and is a sensitive and relatively specific marker for organic GI pathology, with a PPV of 89%. Furthermore, it appears to be a potentially valuable, noninvasive marker of disease activity in IBD.

Cytomegalovirus infection after liver transplantation: viral load as a guide to treating clinical infection.

Background. Quantitative commercial assays for early and accurate detection of active cytomegalovirus (CMV) infection after liver transplantation are widely available. However, meaningful interpretation of viral load measurements is hampered by the lack of definitive cutoff points that correlate with clinically significant disease. Methods. One hundred fifty liver allograft recipients were prospectively monitored for the presence of CMV DNA for the first 12 weeks after orthotopic liver transplantation using the Murex hybrid capture system. The first CMV DNA value after liver transplantation, a weekly rise in CMV DNA (gradient value), and the CMV DNA value on clinical detection of active infection (critical value) were analyzed as risk factors for CMV infection. Results. Forty-four (29.3%) of 150 patients had detectable CMV DNA within 12 weeks of transplantation, and 20 (13.3%) experienced symptomatic CMV infection. Multiple regression analysis demonstrated that baseline CMV DNA level above 10 pg/mL, positive weekly increase in CMV DNA level, and critical CMV DNA level above 13 pg/mL were independent risk factors for clinically significant infection. Using Cox’s multiple regression model, the hazard ratio was 13.9 for baseline CMV DNA above 10 (P =0.0001; 95% confidence interval, 3.5–54) and 13 for a weekly increase in the gradient (P =0.0003; 95% confidence interval, 3.5–50). Critical CMV DNA level above 13 correlated with active infection (100% sensitivity, 98% specificity, 90% positive predictive value, 100% negative predictive value). Conclusion. Baseline and gradient CMV DNA viral load levels correlate with active CMV infection in liver allograft recipients. These data indicate that CMV viral load detection by hybridization methodology is useful in predicting active CMV infection and could be used in a preemptive strategy in liver allograft recipients.

Risk Score Predicting Decline in Renal Function Postliver Transplant: Role in Patient Selection for Combined Liver Kidney Transplantation

Background. A combined liver and kidney transplantation (CLKT) is advocated for selected individuals with chronic kidney disease undergoing liver transplantation (LT). The aim was to develop a risk score to identify the patients whose estimated glomerular filtration rate (eGFR) would decline during the year post-LT to aid future patient selection for CLKT. Methods. A training dataset of LT recipients was identified retrospectively from a prospectively compiled database (2000–2007). The eGFR was calculated at 1 year and those with an eGFR less than 30 mL/min were identified. Variables determined at the LT assessment were analyzed by logistic regression, discriminant function, and area under the receiver operating characteristic curve (AUC) analysis to develop the score. The score was validated in a prospective patient cohort. Results. Three hundred sixty-eight LT recipients were followed up for 1 year (training dataset). The mean eGFR declined by 11.2±23.5 mL/min during that time (P<0.001). A pre-LT risk score to predict an eGFR less than 30 mL/min at 1-year post-LT was generated: −1.8+(1.5 if a history of hypertension)+(0.65×proteinuria in g/24 hr)+(0.013×serum creatinine in &mgr;mol/L)+(0.001×duration of acute kidney injury or eGFR <60 mL/min in days). Reversible renal impairment should first be excluded. Progression was likely with a score more than 2.16. Sensitivity, specificity, and AUC were 99.2%, 100%, and 0.99, respectively. All, but one patient, in the validation cohort (n=149) were correctly classified. Conclusion. This information will complement previously published criteria for CLKT patient selection.

Effectiveness of short-term, enhanced, infection control support in improving compliance with infection control guidelines and practice in nursing homes: a cluster randomized trial.

In this prospective cluster randomized controlled trial we evaluated the impact of short-term provision of enhanced infection control support on infection control practice in nursing homes in South London. Twelve nursing homes were recruited, six each in intervention (300 residents) and control (265 residents) groups. Baseline observations of hand hygiene facilities, environmental cleanliness and safe disposal of clinical waste showed poor compliance in both groups. Post-intervention observations showed improvement in both groups. There was no statistical difference between the two groups in the compliance for hand hygiene facilities (P=0.69); environmental cleanliness (P=0.43) and safe disposal of clinical waste (P=0.96). In both groups, greatest improvement was in compliance with safe disposal of clinical waste and the least improvement was in hand hygiene facilities. Since infection control practice improved in intervention and control groups, we could not demonstrate that provision of short-term, enhanced, infection control support in nursing homes had a significant impact in infection control practice.