The levels of neopterin, biopterin and the neopterin/biopterin ratio in urine from control subjects and patients with Alzheimer’s disease and Down’s syndrome

The levels of neopterin, biopterin and the neopterin/biopterin ratio (N/B) were measured in urine samples taken from normal young and elderly control subjects, exceptionally healthy elderly control subjects classified according to the ‘Senieur’ protocol and patients with Down’s syndrome (DS) or Alzheimer’s disease (AD). The N/B ratio was approximately unity in control groups with the exception of the normal elderly controls. The levels of neopterin and biopterin declined with age in the exceptionally healthy ‘Senieur’ control group. The N/B ratio was elevated in young and old DS patients as a result of the significant increase in neopterin. Neopterin levels were significantly elevated in AD patients compared with the healthy elderly controls, but this did not result in a significant increase in the N/B ratio in these patients. The N/B ratio increased with age in AD patients as a result of a decline in biopterin. These results suggested that there is a cellular immune reponse in DS and AD patients which in DS, may precede the formation of beta-amyloid deposits in the brain. In addition, there may be a deficiency in tetrahydrobiopterin biosynthesis in AD which becomes more marked with age.

Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection

Peer reviewed

Ratio of hemocomponents in massive transfusion and mortality of trauma patients in a university hospital

Background: Nowadays, there are very few studies about massive transfusion in our country. This situation generates the necessity to the elevation of possible new strategies to diminish mortality and its adverse effects. Material and methods: All massive transfusions were evaluated in a retrospective way from October 2010 to October 2012. All diagnosis groups were recorded and the patients were divided into three groups depending on the ratio between packed red blood cells (PRBC) and fresh frozen plasma (FFP) units (ratios ≤2, >2, and without FFP). Their mortality and/or survival were evaluated 30 days after as well as all the factors associated with the event. Results: A total of 69 patients were included (37 trauma patients, 28 gunshot wounds and 4 with lacerated wounds); the groups (ratios ≤2, >2, and no plasma at all) were distributed as follows: 30, 30 and 9 patients each, with an overall mortality rate of 60.8% within 30 days. A lower survival rate (12%) in the no plasma group (P=.015) was found and systolic blood pressure during transfusion had a mean of 67.7 mmHg (P=.012) in this group. Fresh frozen plasma units were 136 and 249 for >2 and ≤2 ratios respectively (P<.01); 85.5% of all patients developed metabolic acidosis during the transfusion, and the number of days in the hospital after the event had a mean of 24.5 days in all patients. Conclusions: High rates of massive transfusion mortality are still being reported in our ield. The use of transfusion strategies contribute to elevate the survival rate in patients with massive transfusion treatment

Variability in the international normalised ratio (INR) in patients with antiphospholipid syndrome and positive lupus anticoagulant: should the INR targets be higher?

El síndrome antifosfolípido es un desorden autoinmune caracterizado por hipercoagulabilidad que requiere terapia anticoagulante como pilar fundamental, siendo la warfarina el tratamiento de elección en los casos que requieren manejo por largos periodos. Sin embargo, los pacientes con anticoagulante lúpico positivo representan un reto porque tienen mayor riesgo de presentar eventos trombóticos, sumado a que el seguimiento con el International Normalized Ratio (INR) no es confiable, ya que estos anticuerpos generan interferencia con las pruebas de laboratorio basadas en fosfolípidos, como es el caso del tiempo de protrombina (PT) con INR basal prolongado, incluso antes del inicio de la terapia anticoagulante. Por tal razón, se ilustra el caso de una paciente con síndrome antifosfolípido primario y anticoagulante lúpico positivo quien ha presentado múltiples episodios trombóticos, a pesar de recibir terapia anticoagulante. Además se hace una revisión de la literatura disponible y se postulan nuevas metas de INR en estos pacientes diferentes de las que se plantean actualmente.

Determinants of pre-hospital care non-usage for patients with emergency care needs [including commentary by Snooks H.]

Objective-To establish the demographic, health status and insurance determinants of pre-hospital ambulance non-usage for patients with emergency medical needs. Methods-Triage category, date of birth, sex, marital status, country of origin, method and time of arrival, ambulance insurance status, diagnosis, and disposal were collected for all patients who presented over a four month period (n=10 229) to the emergency department of a major provincial hospital. Data for patients with urgent (n=678) or critical care needs (n=332) who did not use pre-hospital care were analysed using Poisson regression. Results-Only a small percentage (6.6%) of the total sample were triaged as having urgent medical needs or critical care needs (3.2%). Predictors of usage for those with urgent care needs included age greater than 65 years (prevalence ratio (PR)=0.54; 95% confidence interval (CI)= 0.35 to 0.83), being admitted to intensive care or transferred to another hospital (PR=0.62; 95% CI=0.44 to 0.89) or ward (PR=0.72; 95% CI=0.56 to 0.93) and ambulance insurance status (PR=0.67; 95% CI=052 to 0.86). Sex, marital status, time of day and country of origin were not predictive of usage and non-usage. Predictors of usage for those with critical care needs included age 65 years or greater (PR=0.45; 95% CI=0.25 to 0.81) and a diagnosis of trauma (PR=0.49; 95% CI=0.26 to 0.92). A non-English speaking background was predictive of non-usage (PR=1.98; 95% CI=1.06 to 3.70). Sex, marital status, time of day, triage and ambulance insurance status were not predictive of non-usage. Conclusions-Socioeconomic and medical factors variously influence ambulance usage depending on the severity or urgency of the medical condition. Ambulance insurance status was less of an influence as severity of condition increased suggesting that, at a critical level of urgency, patients without insurance are willing to pay for a pre-hospital ambulance service.

Part 1. Chemical and Physical Restraints in the Management of Mechanically Ventilated Patients in the ICU: Contributing Factors

Chemical and physical restraints are frequently used in the intensive care unit (ICU) to control agitated patients and to prevent self-harm and unplanned extubations. Published work relating to the numerous issues of the care and treatment strategies for these patients remains conflicting and unclear. Literature regarding sedation and chemical restraint reveals a trend towards management with lighter sedation, use of sedation assessment tools and sedation protocols. It remains unclear which treatment is best for agitated and delirious patients, and the evidence on the effect of sedation is conflicting. A large portion of the literature on the use of physical restraint is from general hospital wards and residential homes, and not from the ICU environment. The purpose of this paper is to provide a summary of the existing literature on the use of physical and chemical restraints in the ICU setting. In Part 1 of this two-part paper, the evidence on chemical and physical restraints is explored with specific focus on definition of terms, unplanned

Which components of heart failure programs are effective? A meta-analysis of the outcomes of structured telephone support or telemonitoring as the primary component of heart failure management in 9,560 patients (Abridged Cochrane Review)

Aims--Telemonitoring (TM) and structured telephone support (STS) have the potential to deliver specialised management to more patients with chronic heart failure (CHF), but their efficacy is still to be proven. Objectives To review randomised controlled trials (RCTs) of TM or STS on all- cause mortality and all-cause and CHF-related hospitalisations in patients with CHF, as a non-invasive remote model of specialised disease-management intervention.--Methods and Results--Data sources:We searched 15 electronic databases and hand-searched bibliographies of relevant studies, systematic reviews, and meeting abstracts. Two reviewers independently extracted all data. Study eligibility and participants: We included any randomised controlled trials (RCT) comparing TM or STS to usual care of patients with CHF. Studies that included intensified management with additional home or clinic visits were excluded. Synthesis: Primary outcomes (mortality and hospitalisations) were analysed; secondary outcomes (cost, length of stay, quality of life) were tabulated.--Results: Thirty RCTs of STS and TM were identified (25 peer-reviewed publications (n=8,323) and five abstracts (n=1,482)). Of the 25 peer-reviewed studies, 11 evaluated TM (2,710 participants), 16 evaluated STS (5,613 participants) and two tested both interventions. TM reduced all-cause mortality (risk ratio (RR 0•66 [95% CI 0•54-0•81], p<0•0001) and STS showed similar trends (RR 0•88 [95% CI 0•76-1•01], p=0•08). Both TM (RR 0•79 [95% CI 0•67-0•94], p=0•008) and STS (RR 0•77 [95% CI 0•68-0•87], p<0•0001) reduced CHF-related hospitalisations. Both interventions improved quality of life, reduced costs, and were acceptable to patients. Improvements in prescribing, patient-knowledge and self-care, and functional class were observed.--Conclusion: TM and STS both appear effective interventions to improve outcomes in patients with CHF.

Structured Telephone Support or Telemonitoring Programs for Patients with Chronic Heart Failure

Background: Specialised disease management programmes for chronic heart failure (CHF) improve survival, quality of life and reduce healthcare utilisation. The overall efficacy of structured telephone support or telemonitoring as an individual component of a CHF disease management strategy remains inconclusive. Objectives: To review randomised controlled trials (RCTs) of structured telephone support or telemonitoring compared to standard practice for patients with CHF in order to quantify the effects of these interventions over and above usual care for these patients. Search strategy: Databases (the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database (HTA) on The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED and Science Citation Index Expanded and Conference Citation Index on ISI Web of Knowledge) and various search engines were searched from 2006 to November 2008 to update a previously published non-Cochrane review. Bibliographies of relevant studies and systematic reviews and abstract conference proceedings were handsearched. No language limits were applied. Selection criteria: Only peer reviewed, published RCTs comparing structured telephone support or telemonitoring to usual care of CHF patients were included. Unpublished abstract data was included in sensitivity analyses. The intervention or usual care could not include a home visit or more than the usual (four to six weeks) clinic follow-up. Data collection and analysis: Data were presented as risk ratio (RR) with 95% confidence intervals (CI). Primary outcomes included all-cause mortality, all-cause and CHF-related hospitalisations which were meta-analysed using fixed effects models. Other outcomes included length of stay, quality of life, acceptability and cost and these were described and tabulated. Main results: Twenty-five studies and five published abstracts were included. Of the 25 full peer-reviewed studies meta-analysed, 16 evaluated structured telephone support (5613 participants), 11 evaluated telemonitoring (2710 participants), and two tested both interventions (included in counts). Telemonitoring reduced all-cause mortality (RR 0.66, 95% CI 0.54 to 0.81, P < 0.0001) with structured telephone support demonstrating a non-significant positive effect (RR 0.88, 95% CI 0.76 to 1.01, P = 0.08). Both structured telephone support (RR 0.77, 95% CI 0.68 to 0.87, P < 0.0001) and telemonitoring (RR 0.79, 95% CI 0.67 to 0.94, P = 0.008) reduced CHF-related hospitalisations. For both interventions, several studies improved quality of life, reduced healthcare costs and were acceptable to patients. Improvements in prescribing, patient knowledge and self-care, and New York Heart Association (NYHA) functional class were observed. Authors' conclusions: Structured telephone support and telemonitoring are effective in reducing the risk of all-cause mortality and CHF-related hospitalisations in patients with CHF; they improve quality of life, reduce costs, and evidence-based prescribing.

Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients

Background: High-flow nasal cannulae (HFNC) create positive oropharyngeal airway pressure but it is unclear how their use affects lung volume. Electrical impedance tomography (EIT) allows assessment of changes in lung volume by measuring changes in lung impedance. Primary objectives were to investigate the effects of HFNC on airway pressure (Paw) and end-expiratory lung volume (EELV), and to identify any correlation between the two. Secondary objectives were to investigate the effects of HFNC on respiratory rate (RR), dyspnoea, tidal volume and oxygenation; and the interaction between body mass index (BMI) and EELV. Methods: Twenty patients prescribed HFNC post-cardiac surgery were investigated. Impedance measures, Paw, PaO2/FiO2 ratio, RR and modified Borg scores were recorded first on low flow oxygen (nasal cannula or Hudson face mask) and then on HFNC. Results: A strong and significant correlation existed between Paw and end-expiratory lung impedance (EELI) (r=0.7, p<0.001). Compared with low flow oxygen, HFNC significantly increased EELI by 25.6% (95% CI 24.3, 26.9) and Paw by 3.0 cmH2O (95% CI 2.4, 3.7). RR reduced by 3.4 breaths per minute (95% CI 1.7, 5.2) with HFNC use, tidal impedance variation increased by 10.5% (95% CI 6.1, 18.3) and PaO2/FiO2 ratio improved by 30.6 mmHg (95% CI 17.9, 43.3). HFNC improved subjective dyspnoea scoring (p=0.023). Increases in EELI were significantly influenced by BMI, with larger increases associated with higher BMIs (p<0.001). Conclusions: This study suggests that HFNC improve dyspnoea and oxygenation by increasing both EELV and tidal volume, and are most beneficial in patients with higher BMIs.

Editoral : Correspondence regarding Anker SD, Koehler F, Abraham WT. Telemedicine and remote management of patients with heart failure. The Lancet 2011; 378: 731–39. Published 20 August 2011.

We read the excellent review of telemonitoring in chronic heart failure (CHF)1 with interest and commend the authors on the proposed classification of telemedical remote management systems according to the type of data transfer, decision ability and level of integration. However, several points require clarification in relation to our Cochrane review of telemonitoring and structured telephone support2. We included a study by Kielblock3. We corresponded directly with this study team specifically to find out whether or not this was a randomised study and were informed that it was a randomised trial, albeit by date of birth. We note in our review2 that this randomisation method carries a high risk of bias. Post-hoc metaanalyses without these data demonstrate no substantial change to the effect estimates for all cause mortality (original risk ratio (RR) 0·66 [95% CI 0·54, 0·81], p<0·0001; revised RR 0·72 [95% CI 0·57, 0·92], p=0·008), all-cause hospitalisation (original RR 0·91 [95% CI 0·84, 0·99] p=0·02; revised RR 0.92 [95% CI 0·84, 1·02], p=0·10 ) or CHF-related hospitalisation (original RR 0·79 [95% CI 0·67, 0·94] p=0·008; revised RR 0·75 [95% CI 0·60, 0·94] p=0·01). Secondly, we would classify the Tele-HF study4, 5 as structured telephone support, rather than telemonitoring. Again, inclusion of these data alters the point-estimate but not the overall result of the meta-analyses4. Finally, our review2 does not include invasive telemonitoring as the search strategy was not designed to capture these studies. Therefore direct comparison of our review findings with recent studies of these interventions is not recommended.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

CD4+ tumor infiltrating lymphocytes are prognostic and independent of R-IPI in patients with DLBCL receiving R-CHOP chemo-immunotherapy

Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P = 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD4+ T-cell infiltration as the most significant predictor of outcome with ≥23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P = 0.007) and OS (P = 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD4+ T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P = 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP.

Perianal disease combined with NOD2 genotype predicts need for IBD-related surgery in Crohn’s Disease patients from a population-based cohort

Background: Patients with Crohn’s disease (CD) often require surgery at some stage of disease course. Prediction of CD outcome is influenced by clinical, environmental, serological, and genetic factors (eg, NOD2). Being able to identify CD patients at high risk of surgical intervention should assist clinicians to decide whether or not to prescribe early aggressive treatment with immunomodulators. Methods: We performed a retrospective analysis of selected clinical (age at diagnosis, perianal disease, active smoking) and genetic (NOD2 genotype) data obtained for a population-based CD cohort from the Canterbury Inflammatory Bowel Disease study. Logistic regression was used to identify predictors of complicated outcome in these CD patients (ie, need for inflammatory bowel disease-related surgery). Results: Perianal disease and the NOD2 genotype were the only independent factors associated with the need for surgery in this patient group (odds ratio=2.84 and 1.60, respectively). By combining the associated NOD2 genotype with perianal disease we generated a single “clinicogenetic” variable. This was strongly associated with increased risk of surgery (odds ratio=3.84, P=0.00, confidence interval, 2.28-6.46) and offered moderate predictive accuracy (positive predictive value=0.62). Approximately 1/3 of surgical outcomes in this population are attributable to the NOD2+PA variable (attributable risk=0.32). Conclusions: Knowledge of perianal disease and NOD2 genotype in patients presenting with CD may offer clinicians some decision-making utility for early diagnosis of complicated CD progression and initiating intensive treatment to avoid surgical intervention. Future studies should investigate combination effects of other genetic, clinical, and environmental factors when attempting to identify predictors of complicated CD outcomes.

Evaluating the dosimetric effect of treatment-induced changed in virally mediated head and neck cancer patients

Introduction Patients with virally mediated head and neck cancer (VMHNC) often present with advanced nodal disease that is highly radioresponsive as demonstrated by tumour and nodal regression during treatment. The resultant changes may impact on the planned dose distribution and so adversely affect the therapeutic ratio. The aim of this study was to evaluate the dosimetric effect of treatment-induced anatomical changes in VMHNC patients who had undergone a re-plan. Methods Thirteen patients with virally mediated oropharyngeal or nasopharyngeal cancer who presented for definitive radiotherapy between 2005 and 2010 and who had a re-plan generated were investigated. The dosimetric effect of anatomical changes, was quantified by comparing dose volume histograms (DVH) of primary and nodal gross target volumes and organs at risk (OAR), including spinal cord and parotid glands, from the original plan and a comparison plan. Results Eleven 3DCRT and 2 IMRT plans were evaluated. Dose to the spinal cord and brainstem increased by 4.1% and 2.6%, respectively. Mean dose to the parotid glands also increased by 3.5%. In contrast, the dose received by 98% of the primary and nodal gross tumour volumes decreased by 0.15% and 0.3%, respectively when comparing the initial treatment plan to the comparison plan. Conclusion In this study, treatment-induced anatomical changes had the greatest impact on OAR dose with negligible effect on the dose to nodal gross tumour volumes. In the era of intensity modulated radiotherapy (IMRT), accounting for treatment-induced anatomical changes is important as focus is placed on minimising the acute and long-term side effects of treatment.

Protocol for a randomised blocked design study using telephone and text-messaging to support cardiac patients with diabetes : a cross cultural international collaborative project

Background The prevalence of type 2 diabetes is rising internationally. Patients with diabetes have a higher risk of cardiovascular events accounting for substantial premature morbidity and mortality, and health care expenditure. Given healthcare workforce limitations, there is a need to improve interventions that promote positive self-management behaviours that enable patients to manage their chronic conditions effectively, across different cultural contexts. Previous studies have evaluated the feasibility of including telephone and Short Message Service (SMS) follow up in chronic disease self-management programs, but only for single diseases or in one specific population. Therefore, the aim of this study is to evaluate the feasibility and short-term efficacy of incorporating telephone and text messaging to support the care of patients with diabetes and cardiac disease, in Australia and in Taiwan. Methods/design A randomised controlled trial design will be used to evaluate a self-management program for people with diabetes and cardiac disease that incorporates the use of simple remote-access communication technologies. A sample size of 180 participants from Australia and Taiwan will be recruited and randomised in a one-to-one ratio to receive either the intervention in addition to usual care (intervention) or usual care alone (control). The intervention will consist of in-hospital education as well as follow up utilising personal telephone calls and SMS reminders. Primary short term outcomes of interest include self-care behaviours and self-efficacy assessed at baseline and four weeks. Discussion If the results of this investigation substantiate the feasibility and efficacy of the telephone and SMS intervention for promoting self management among patients with diabetes and cardiac disease in Australia and Taiwan, it will support the external validity of the intervention. It is anticipated that empirical data from this investigation will provide valuable information to inform future international collaborations, while providing a platform for further enhancements of the program, which has potential to benefit patients internationally.