Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome

Objective

Adverse events (AEs) are health related events, reported by participants in clinical trials. We describe AEs in the PACE trial of treatments for chronic fatigue syndrome (CFS) and baseline characteristics associated with them.

Methods

AEs were recorded on three occasions over one year in 641 participants. We compared the numbers and nature of AEs between treatment arms of specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). We examined associations with baseline measures by binary logistic regression analyses, and compared the proportions of participants who deteriorated by clinically important amounts.

Results

Serious adverse events and reactions were infrequent. Non-serious adverse events were common; the median (quartiles) number was 4 (2, 8) per participant, with no significant differences between treatments (P = .47). A greater number of NSAEs were associated with recruitment centre, and baseline physical symptom count, body mass index, and depressive disorder. Physical function deteriorated in 39 (25%) participants after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC (P < .001), with no significant differences in worsening fatigue.

Conclusions

The numbers of adverse events did not differ significantly between trial treatments, but physical deterioration occurred most often after APT. The reporting of non-serious adverse events may reflect the nature of the illness rather than the effect of treatments. Differences between centres suggest that both standardisation of ascertainment methods and training are important when collecting adverse event data.     

The presence of water influences reproductive function in the song sparrow (Melospiza melodia morphna)

Cumulative evidence indicates that song sparrows, Melospiza melodia morphna, of western Washington State prefer territories close to water. Densities of territories were higher within 50m of open water and analysis of stomach contents revealed aquatic organisms. An unusually dry period (less open water) in May and June 1997 had no effect on latency of territorial males to respond to a simulated territorial intrusion (STI), but the number of songs and closest approach to the decoy were lower than those recorded in June 1988 (no major dry periods). A laboratory experiment was conducted in which males and females were exposed to long days to stimulate reproductive development. One group received a bath with water daily and the other group received a dry bath (both groups had ad libitum access to drinking water through a glass tube). Birds with a dry bath tended to show reduced photoperiodically-induced gonadal growth compared with birds that had access to water in the bath. Plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increased following photostimulation in all groups. However, LH levels were higher in females with access to water. There were no differences in hormone levels in any of the other groups. Taken together these novel data indicate that presence and access to open water could be an important environmental cue for song sparrows in western Washington State. Implications for global climate change and droughts are suggested.     

Tumor-specific but not nonspecific cell-free circulating DNA can be used to monitor disease response in lymphoma

Recently, nontumor specific circulating DNA was shown to be elevated in a broad range of lymphomas, implicating a role as a potential biomarker. Epstein-Barr virus' (EBV) presence within a proportion of lymphomas implies EBV-DNA has potential as a lymphoma-specific disease response biomarker. However, application would be restricted to EBV-associated lymphomas. Neither detailed comparison has been performed of lymphoma-specific versus nonspecific DNA as disease response biomarkers nor have the kinetics of circulating DNA during treatment been established, and the optimal methodology remains unknown. We prospectively evaluated DNA levels and clinical response of 63 lymphoma patients. DNA was measured in paired serum, plasma, and cell samples at five predetermined time-points taken prior, during and following treatment. Both cell-free (c-f) circulating EBV-DNA (in EBV-associated lymphoma) and nonspecific c-f DNA levels (in all lymphomas) were elevated and discriminatory at presentation compared to healthy controls. Nonspecific c-f DNA was significantly associated with baseline serum lactate dehydrogenase. Within EBV-associated lymphomas at presentation, there was a strong correlation between specific and nonspecific circulating c-f DNA (r = 0.9, P < 0.0001). However, only c-f EBV-DNA correlated with clinical/radiological response. In addition, c-f EBV-DNA, and not nonspecific c-f DNA, provided an early marker of relapsed and refractory disease. Serum versus plasma, and single versus multiple-copy EBV-gene targets were equivalent. Lymphoma-specific DNA is a disease response biomarker; however, nonspecific DNA reflected neither lymphoma-specific DNA nor therapeutic response. Lymphoma disease response can be monitored by blood tests, but new lymphoma-specific biomarkers need to be identified to broaden applicability.     

Subcellular Biochemical Investigation of Purkinje Neurons Using Synchrotron Radiation Fourier Transform Infrared Spectroscopic Imaging with a Focal Plane Array Detector

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