Current Pyuria Cutoffs Promote Inappropriate Urinary Tract Infection Diagnosis in Older Women

Background: Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women. Methods: Women ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity–specificity pairs were derived from a receiver operating characteristic curve. Results: We included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%. Conclusions: The degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women

Heterogeneous Adaptive Trajectories of Small Populations on Complex Fitness Landscapes

Background Small populations are thought to be adaptively handicapped, not only because they suffer more from deleterious mutations but also because they have limited access to new beneficial mutations, particularly those conferring large benefits. Methodology/Principal Findings Here, we test this widely held conjecture using both simulations and experiments with small and large bacterial populations evolving in either a simple or a complex nutrient environment. Consistent with expectations, we find that small populations are adaptively constrained in the simple environment; however, in the complex environment small populations not only follow more heterogeneous adaptive trajectories, but can also attain higher fitness than the large populations. Large populations are constrained to near deterministic fixation of rare large-benefit mutations. While such determinism speeds adaptation on the smooth adaptive landscape represented by the simple environment, it can limit the ability of large populations from effectively exploring the underlying topography of rugged adaptive landscapes characterized by complex environments. Conclusions Our results show that adaptive constraints often faced by small populations can be circumvented during evolution on rugged adaptive landscapes

Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies

Measurements of the cross section for exclusive virtual-photoproduction of rho^0 mesons from hydrogen are reported. The data were collected by the HERMES experiment using 27.5 GeV positrons incident on a hydrogen gas target in the HERA storage ring. The invariant mass W of the photon-nucleon system ranges from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with most of the previous data at W > 4 GeV are well described by a model that infers the W-dependence of the cross section from the dependence on the Bjorken scaling variable x of the unpolarized structure function for deep-inelastic scattering. In addition, a model calculation based on Off-Forward Parton Distributions gives a fairly good account of the longitudinal component of the rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class. Revisions: curves added to Fig. 1, several clarifications added to tex

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p &lt; 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections

Molecular diagnostics of intestinal parasites in returning travellers

A new diagnostic strategy was assessed for the routine diagnosis of intestinal parasites in returning travellers and immigrants. Over a period of 13 months, unpreserved stool samples, patient characteristics and clinical data were collected from those attending a travel clinic. Stool samples were analysed on a daily basis by microscopic examination and antigen detection (i.e. care as usual), and compared with a weekly performed multiplex real-time polymerase chain reaction (PCR) analysis on Entamoeba histolytica, Giardia lamblia, Cryptosporidium and Strongyloides stercoralis. Microscopy and antigen assays of 2,591 stool samples showed E. histolytica, G. lamblia, Cryptosporidium and S. stercoralis in 0.3, 4.7, 0.5 and 0.1% of the cases, respectively. These detection rates were increased using real-time PCR to 0.5, 6.0, 1.3 and 0.8%, respectively. The prevalence of ten additional pathogenic parasite species identified with microscopy was, at most, 0.5%. A pre-selective decision tree based on travel history or gastro-intestinal complaints could not be made. With increased detection rates at a lower workload and the potential to extend with additional parasite targets combined with fully automated DNA isolation, molecular high-throughput screening could eventually replace microscopy to a large extent

Psychosocial interventions for patients with advanced cancer – a systematic review of the literature

Advanced cancer is associated with emotional distress, especially depression and feelings of sadness. To date, it is unclear which is the most effective way to address these problems. This review focuses on the effects of psychosocial interventions on the quality of life (QoL) of patients with advanced cancer. It was hypothesised that patients will benefit from psychosocial interventions by improving QoL, especially in the domain of emotional functioning. The review was conducted using systematic review methodology involving a systematic search of the literature published between 1990 and 2002, quality assessment of included studies, systematic data extraction and narrative data synthesis. In all, 10 randomised controlled studies involving 13 trials were included. Overall interventions and outcome measures across studies were heterogeneous. Outcome measures, pertaining to the QoL dimension of emotional functioning, were most frequently measured. A total of 12 trials evaluating behaviour therapy found positive effects on one or more indicators of QoL, for example, depression. The results of the review support recommendation of behaviour therapy in the care of patients with advanced cancer

Psychosocial interventions for patients with advanced cancer – a systematic review of the literature

Advanced cancer is associated with emotional distress, especially depression and feelings of sadness. To date, it is unclear which is the most effective way to address these problems. This review focuses on the effects of psychosocial interventions on the quality of life (QoL) of patients with advanced cancer. It was hypothesised that patients will benefit from psychosocial interventions by improving QoL, especially in the domain of emotional functioning. The review was conducted using systematic review methodology involving a systematic search of the literature published between 1990 and 2002, quality assessment of included studies, systematic data extraction and narrative data synthesis. In all, 10 randomised controlled studies involving 13 trials were included. Overall interventions and outcome measures across studies were heterogeneous. Outcome measures, pertaining to the QoL dimension of emotional functioning, were most frequently measured. A total of 12 trials evaluating behaviour therapy found positive effects on one or more indicators of QoL, for example, depression. The results of the review support recommendation of behaviour therapy in the care of patients with advanced cancer

The reliability of postural balance measures in single and dual tasking in elderly fallers and non-fallers

BACKGROUND: The purpose of this study was to determine the reliability of a forceplate postural balance protocol in a group of elderly fallers and non-fallers. The measurements were tested in single and dual-task conditions, with and without vision. METHODS: 37 elderly (mean age 73 +/- 6 years) community-dwellers were included in this study. All were tested in a single (two-legged stance) and in a dual-task (two-legged stance while counting backwards aloud in steps of 7's) condition, with and without vision. A forceplate was used for registering postural variables: the maximal and the root-mean-square amplitude in medio-lateral (Max-ML, RMS-ML) and antero-posterior (Max-AP, RMS-AP) direction, mean velocity (MV), and the area of the 95% confidence ellipse (AoE). Reliability of the test protocol was expressed with intraclass correlation coefficients (ICC), with 95% limits of agreement (LoA), and with the smallest detectable difference (SDD). RESULTS: The ICCs for inter-rater reliability and test-retest reliability of the balance variables were r = 0.70-0.89. For the variables Max-AP and RMS-AP the ICCs were r = 0.52-0.74. The SDD values were for variable Max-ML and Max-AP between 0.37 cm and 0.83 cm, for MV between 0.48 cm/s and 1.2 cm/s and for AoE between 1.48 cm2 and 3.75 cm2. The LoA analysis by Bland-Altman plots showed no systematic differences between test-retest measurements. CONCLUSION: The study showed good reliability results for group assessment and no systematic errors of the measurement protocol in measuring postural balance in the elderly in a single-task and dual-task condition

Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin

Aims/hypothesis Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. Methods Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes. Results Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified. Conclusion/interpretation Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin