The PACE trial generated much criticism due to the broad Oxford criteria patient selection, the standards of outcome effectiveness were lowered during the study and that re-analysis of the data did not support the magnitude of improvements initially reported.Unlike pacing, APT is based on the cognitive behavioral model  of chronic fatigue syndrome and involves increasing activity levels, which it states may temporarily increase symptoms. In APT, the patient first establishes a baseline level of activity, which can be carried out consistently without any post-exertional malaise ("crashes"). APT states that persons should plan to increase their activity, as able. However, APT also requires patients to restrict their activity level to only 70% of what they feel able to do, while also warning against too much rest. This has been described as contradictory, and Jason states that in comparison with pacing, this 70% limit restricts the activities that patients are capable of and results in a lower level of functioning. Jason and Goudsmit, who first described pacing and the energy envelope theory for CFS, have both criticized APT for being inconsistent with the principles of pacing and highlighted significant differences. APT was promoted by Action for ME, the patient charity involved in the PACE trial, until 2019. Rintatolimod
Rintatolimod is a double-stranded RNA drug developed to modulate an antiviral immune reaction through activation of toll-like receptor 3. In several clinical trials of CFS, the treatment has shown a reduction in symptoms, but improvements were not sustained after discontinuation.
Each papule corresponds to the penetration site of a single parasite. After locating a bird, the parasite penetrates through the skin (usually the feet), dropping the forked tail in the process. Inside the circulatory system, the immature worms (schistosomula) develop into mature male and female worms, mate and migrate through the hosts circulatory system (or nervous system in case of T. regenti) to the final location (veins feeding the gastrointestinal tract) within the host body. There they lay eggs in the small veins in the intestinal mucosa from which they make their way into the lumen of the gut, and are dumped into the water when the bird defecates. One European species, Trichobilharzia regenti, instead infects the bird hosts nasal tissues and larvae hatch from the eggs directly in the tissue during drinking/feeding of the infected birds. Risk factors
Humans usually become infected after swimming in slow-moving rivers, lakes or ponds. Some laboratory evidence indicates snails shed cercariae most intensely in the morning and on sunny days, and exposure to water in these conditions may therefore increase risk. Duration of swimming is correlated with increased risk of infection in Europe and North America, and shallow inshore waters may harbour higher densities of cercariae than open waters offshore. Onshore winds are thought to cause cercariae to accumulate along shorelines.