Knee disorders in primary care: design and patient selection of the HONEUR knee cohort.

BACKGROUND: Knee complaints are a frequent reason for consultation in general practice. These patients constitute a specific population compared to secondary care patients. However, information to base treatment decisions on is generally derived from specialistic settings. Our cohort study is aimed at collecting knowledge about prognosis and prognostic factors of knee complaints presented in a primary care setting. This paper describes the methods used for data collection, and discusses potential selectiveness of patient recruitment. METHODS: This is a descriptive prospective cohort study with one-year follow-up. 40 Dutch GPs recruited consecutive patients with incident knee complaints aged 12 years and above from October 2001 to October 2003. Patients were assessed with questionnaires and standardised physical examinations. Additional measurements of subgroups included MRI for recent knee traumas and device assessed function measurements for non-traumatic patients. After the inclusion period we retrospectively searched the computerized medical files of participating GPs to obtain a sample to determine possible selective recruitment. We assessed differences in proportions of gender, traumatic onset of injury and age groups between participants and non-participants using Odds Ratios (OR) and 95% confidence intervals. RESULTS: We recruited 1068 patients. In a sample of 310 patients visiting the GP, we detected some selective recruitment, indicating an underrepresentation of patients aged 12 to 35 years (OR 1.70; 1.15-2.77), especially among men (OR 2.16; 1.12-4.18). The underrepresentation of patients with traumatic onset of injury was not statistically significant. CONCLUSION: This cohort is unique in its size, setting, and its range of both age and type of knee complaints. We believe the detected selective recruitment is unlikely to introduce significant bias, as the cohort will be divided into subgroups according to age group or traumatic onset of injury for future analyses. However, the underrepresentation of men in the age group of 12 to 35 years of age warrants caution. Based on the available data, we believe our cohort is an acceptable representation of patients with new knee complaints consulting the GP, and we expect no problems with extrapolation of the results to the general Dutch population

Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction

Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics

The probable mechanisms of brain damage and epilepsy in febrile convulsions, Singapore syndrome and Reye's syndrome

Acta Paediatrica Japonica (Overseas Edition)313245-258APDJ

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease

BACKGROUND: The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer. METHODS: Cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure. We identified 69,984 patients with localized prostate cancer diagnosed from 2001 to 2015 treated with surgery or radiation. We coded receipt of TT after treatment as a time-dependent covariate; used the National Death Index to identify cause of death; and defined biochemical recurrence as PSA > 0.2 ng/mL after surgery and nadir + 2 ng/mL after radiation. We analyzed recurrence and mortality using cumulative incidence curves, Fine-Gray competing risk regression, and Cox regression. RESULTS: This cohort included 28,651 surgery patients and 41,333 radiation patients, of whom 469 (1.64%) and 543 (1.31%), respectively, received TT with a median follow-up of 6.95 years. Comparing testosterone users to nonusers, there were no between-group differences in biochemical recurrence, prostate cancer-specific mortality, or overall mortality after surgery [hazard ratios (HR): 1.07; HR: 0.72 (p = 0.43); and HR: 1.11 (p = 0.43), respectively] or radiation [HR: 1.07; HR: 1.02 (p = 0.95); and HR: 1.02 (p = 0.86), respectively]. Limitations included lack of detailed data on TT duration and serum testosterone concentrations. CONCLUSIONS: In this multi-ethnic national cohort, TT did not increase the risks of biochemical recurrence or prostate cancer-specific or overall mortality after surgery or radiation. These data suggest that TT is safe in appropriate men after definitive treatment of localized prostate cancer