Topical photodynamic therapy at low fluence rates--theory and practice.

Photodynamic Therapy (PDT), with topically applied 5-aminolaevulinic acid as the photosensitiser, is an effective treatment for various malignant and pre-malignant skin conditions. Several studies have shown the importance of fluence rate as well as fluence in the efficacy of PDT. We propose a measure of PDT efficacy, Photodynamic Damage Dose (PDD), which uses the product of instantaneous fluence rates, photosensitiser concentrations and oxygen concentrations in its calculation. We derive a qualitative numerical model of PDT and verify it by demonstrating an inverse fluence rate effect, increased efficacy of fractionated PDT, PDT induced hypoxia, and the dependence of photobleaching on fluence rate under certain circumstances. We recommend that fluence, fluence rate and any fractionation regime used should be detailed when reporting a trial as altering any of these has significant effects on PDT efficacy. The model predicts that low fluence rate irradiations should be as effective as high fluence rate irradiations if carried out over the same length of time. To test this we build a light emitting diode-based lamp (fluence rate of 7 mW cm(-2) at 635 nm) and used it to treat 32 superficial basal cell carcinomas on 22 patients (30 min treatment time, fluence 12.6 J cm(-2)). The complete response rate at one year was 84%, which is comparable to that achieved using higher fluence rate sources for similar treatment times. We conclude that this robust, inexpensive light source is effective for topical PDT.

Functional assessment of the elderly. A comparison of standard instruments with clinical judgment.

Using specific instruments and scales to measure mental status, nutritional state, visual acuity, gait, and activities of daily living, we studied 79 medical inpatients aged 70 years or older. We then interviewed the patients' primary physicians and nurses and asked them to rate their patients. The prevalence of functional impairment was high: 25 (32%) of the 79 patients were mentally impaired, 31 (39%) were malnourished, 18 (23%) were visually impaired, 31 (39%) had impaired gait, and 23 (29%) had problems with continence. Although clinicians recognized severe impairments, the sensitivity of their clinical judgment was poor in detecting moderate impairment in four categories: mental status sensitivity was 28% (5/18); nutrition, 54% (14/26); vision, 27% (4/15); and continence, 42% (5/12). With clinical judgment alone, physicians and nurses correctly identify severe impairment, but the more prevalent moderate impairments in mental status, nutrition, vision, and continence are poorly recognized. Comprehensive functional assessment instruments can detect these moderate impairments, which may be remediable through early intervention.