Gastric Acid Suppressive Therapy and Community-Acquired Pneumonia, Etiology and Outcome

Background: Community acquired pneumonia (CAP) is an infection of the pulmonary parenchyma that can be caused by various microbial pathogens. Co-morbidity and medication are related to specific pathogens. Patients on gastric acid suppressive therapy have an increased risk to develop CAP. We aimed to assess whether there are specific pathogens independently associated with gastric acid suppressive therapy and its impact on infection severity. Methods: From December 2007 to January 2010, all subjects consulting the emergency care unit of a general hospital in the south of the Netherlands with a suspected CAP were prospectively registered. Each patient underwent chest radiography. Sputum, urine, nose swabs and blood samples were obtained for microbial culture, antigen detection and polymerase chain reaction techniques, respectively. To study the severity of CAP upon presentation, the validated CURB-65 score was calculated. Furthermore, we assessed hospital or intensive care admission, length of hospitalization and in-hospital mortality. We evaluated the association between use of acid suppressive therapy and microbial aetiology of CAP and severity of illness with logistic regression analysis. Results: The final cohort comprised 463 patients with CAP, defined as presence of infiltrate on chest radiography and/ or microbial aetiology. Overall 136 patients (29%) used acid suppressive therapy, mainly proton pump inhibitors (97%). Patients with acid suppressive therapy more frequently had an infection with Streptococcus pneumoniae (28% vs. 14%) and Haemophilus influenzae (10% vs. 6%), and less frequently with Coxiella burnetii (8% vs. 19%) or H1N1 influenza A virus (2% vs. 7%) in comparison to those without acid suppressive therapy. After adjustment for baseline differences, the risk of proton pump inhibitor users being infected with S. pneumonia was 2.18 times (95%Confidence Interval(CI): 1.2-3.6) higher compared to those not on acid suppressive therapy. Patients using more than one defined daily dose of a PPI had a 1.48-fold increased risk of a S. pneumoniae infection compared with patients using the defined daily dose (95%CI:1.1-2.0). No risk between PPI use and any other microbial pathogen was found. Patients with acid suppressive therapy had on average higher CURB-65 scores, longer hospital stay and subsequently a case fatality rate of 11% vs. 4% compared to those not using acid suppressive therapy. Conclusions. Proton pump inhibitor therapy predisposes with community acquired S. pneumoniae pneumonia, and was associated with higher morbidity

Multi-classifier prediction of knee osteoarthritis progression from incomplete imbalanced longitudinal data

Conventional inclusion criteria used in osteoarthritis clinical trials are not very effective in selecting patients who would benefit from a therapy being tested. Typically majority of selected patients show no or limited disease progression during a trial period. As a consequence, the effect of the tested treatment cannot be observed, and the efforts and resources invested in running the trial are not rewarded. This could be avoided, if selection criteria were more predictive of the future disease progression. In this article, we formulated the patient selection problem as a multi-class classification task, with classes based on clinically relevant measures of progression (over a time scale typical for clinical trials). Using data from two long-term knee osteoarthritis studies OAI and CHECK, we tested multiple algorithms and learning process configurations (including multi-classifier approaches, cost-sensitive learning, and feature selection), to identify the best performing machine learning models. We examined the behaviour of the best models, with respect to prediction errors and the impact of used features, to confirm their clinical relevance. We found that the model-based selection outperforms the conventional inclusion criteria, reducing by 20-25% the number of patients who show no progression. This result might lead to more efficient clinical trials.Comment: 22 pages, 12 figures, 10 table

Study protocol: effect of infection, Modic and inflammation on clinical outcomes in surgery for radiculopathy (EIMICOR)

Background: Evidence indicates that inflammatory processes are involved in radicular pain as well as in resorption of herniated disc tissue. Furthermore there are indications that the presence of vertebral end plate pathology (Modic changes; MC) is associated with a negative effect on inflammation. It is hypothesized that in patients with MC, the (possibly bacterial induced) inflammation will be accompanied by pro inflammatory cytokines that worsen the outcome, and that in patients without MC, the inflammation is accompanied by cytokines that induce a resorption process to accelerate recovery.Methods: This prospective cohort study will include 160 lumbar and 160 cervical patients (total of 320), which are scheduled for surgery for either a lumbar or cervical herniated disc with ages between 18 and 75. The main and interaction effects of local bacterial infection (culture), inflammatory cells in disc material (immunohistology), MC (MRI), and blood biomarkers indicating inflammation or infection (blood sample evaluation) will be evaluated. Clinical parameters to be evaluated are leg pain on the 11 point NRS pain scale, Oswestry (lumbar spine) or Neck (cervical spine) Disability Index, Global Perceived Recovery, Womac Questionnaire, and medication status, at baseline, and after 6, 16, 26 and 52 weeks.Discussion: Gaining insight in the aetiology of pain and discomfort in radiculopathy caused by a herniated disc could lead to more effective management of patients. If the type of inflammatory cells shows to be of major influence on the rate of recovery, new immunomodulating treatment strategies can be developed to decrease the duration and intensity of symptoms. Moreover, identifying a beneficial inflammatory response in the disc through a biomarker in blood could lead to early identification of patients whose herniations will resorb spontaneously versus those that require surgery.OV

Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study

<p>Abstract</p> <p>Background</p> <p>Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.</p> <p>Methods/Design</p> <p>In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.</p> <p>Discussion</p> <p>Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN16211826.</p

Longitudinal evaluation of synovial fluid and synovial fluid MSC transcript changes in subjects undergoing joint distraction.

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Risk factors for acute respiratory tract infections in general practitioner patients in The Netherlands: a case-control study

<p>Abstract</p> <p>Background</p> <p>Acute respiratory tract infections (ARTI) are an important public health problem. Improved identification of risk factors might enable targeted intervention. Therefore we carried out a case-control study with the aim of identifying environmental risk factors for ARTI consultations in the Dutch general population.</p> <p>Methods</p> <p>A subset of patients visiting their GP in the period of 2000–2003 with an ARTI (cases) and age-matched controls (visiting for other complaints) were included in a case-control study. They were asked to complete a questionnaire about potential risk factors. Conditional logistic regression was used to calculate odds ratio's (OR) and 95% confidence intervals (CI) to estimate the independent effect of potential risk factors.</p> <p>Results</p> <p>A total of 493 matched pairs of case and control subjects were enrolled. Exposure to persons with respiratory complaints, both inside and outside the household, was found to be an independent risk factor for visiting a GP with an ARTI (respectively OR_adj= 1.9 and OR_adj= 3.7). Participants exposed to dampness or mould at home (OR_adj=0.5) were significantly less likely to visit their GP. In accordance with the general risk of consultations for ARTI, participants with a laboratory-confirmed ARTI who were exposed to persons with respiratory complaints outside the household were also significantly more likely to visit their GP (OR_adj=2.5).</p> <p>Conclusion</p> <p>This study confirmed that heterogeneity in the general population as well as in pathogens causing ARTI makes it complicated to detect associations between potential risk factors and respiratory infections. Whereas it may be difficult to intervene on the risk posed by exposure to persons with respiratory complaints, transmission of ARTI in the general population might be reduced by improved hygienic conditions.</p