Policy-makers are increasingly turning to behavioural science for insights about how to improve citizens' decisions and outcomes1. Typically, different scientists test different intervention ideas in different samples using different outcomes over different time intervals2. The lack of comparability of such individual investigations limits their potential to inform policy. Here, to address this limitation and accelerate the pace of discovery, we introduce the megastudy-a massive field experiment in which the effects of many different interventions are compared in the same population on the same objectively measured outcome for the same duration. In a megastudy targeting physical exercise among 61,293 members of an American fitness chain, 30 scientists from 15 different US universities worked in small independent teams to design a total of 54 different four-week digital programmes (or interventions) encouraging exercise. We show that 45% of these interventions significantly increased weekly gym visits by 9% to 27%; the top-performing intervention offered microrewards for returning to the gym after a missed workout. Only 8% of interventions induced behaviour change that was significant and measurable after the four-week intervention. Conditioning on the 45% of interventions that increased exercise during the intervention, we detected carry-over effects that were proportionally similar to those measured in previous research3-6. Forecasts by impartial judges failed to predict which interventions would be most effective, underscoring the value of testing many ideas at once and, therefore, the potential for megastudies to improve the evidentiary value of behavioural science.
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Latent syphilis is defined as syphilis characterized by seroreactivity without other evidence of primary, secondary, or tertiary disease. Persons who have latent syphilis and who acquired syphilis during the preceding year are classified as having early latent syphilis (early nonprimary, nonsecondary). Persons can receive a diagnosis of early latent syphilis if, during the year preceding the diagnosis, they had a documented seroconversion or a sustained (>2 weeks) fourfold or greater increase in nontreponemal test titers in a previously treated person; unequivocal symptoms of primary or secondary syphilis; or a sex partner documented to have primary, secondary, or early latent syphilis. In addition, for persons with reactive nontreponemal and treponemal tests whose only possible exposure occurred during the previous 12 months, early latent syphilis can be assumed.
Quantitative nontreponemal serologic tests should be repeated at 6, 12, and 24 months. These serologic titers should be compared with the titer at the time of treatment. Persons with at least a fourfold sustained increase in nontreponemal test titer persisting for >2 weeks or who experienced signs or symptoms attributable to primary or secondary syphilis were likely reinfected or experienced treatment failure. These persons should be retreated and reevaluated for HIV infection. Among persons who have neurologic findings after a thorough neurologic examination or among persons with no neurologic findings and no sexual exposure during the previous year, a CSF examination is recommended. Treatment should be guided by CSF findings. Among persons with no neurologic findings after neurologic examination and who are sexually active, treatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks is recommended.
Optimal management of persons who have less than a fourfold decrease in titers 24 months after treatment (i.e., an inadequate serologic response) is unclear, especially if the initial titer was 1:32) does not decrease at least fourfold 24 months after treatment, retreatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks is recommended. Because treatment failure might be the result of unrecognized CNS infection, CSF examination can be considered in such situations where follow-up is uncertain or initial high titers do not decrease after 24 months.
Persons with HIV infection and primary or secondary syphilis should be evaluated clinically and serologically for possible treatment failure at 3, 6, 9, 12, and 24 months after therapy; those who meet the criteria for treatment failure (i.e., signs or symptoms that persist or recur or a sustained [>2 weeks] fourfold or greater increase in titer) should be managed in the same manner as persons without HIV infection (i.e., depending on history of sexual activity and on findings of neurologic examination, either repeat treatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks or CSF examination and repeat treatment guided by CSF findings) (see Primary and Secondary Syphilis).
In addition, CSF examination and retreatment can be considered for persons whose nontreponemal test titers do not decrease fourfold within 24 months of therapy. If CSF examination is normal, treatment with benzathine penicillin G administered as 2.4 million units IM at weekly intervals for 3 weeks is recommended. Serologic titers might not decrease despite a negative CSF examination and a repeated 3-week course of therapy (599). Especially if the initial nontreponemal titer is low (
Patients with HIV and latent syphilis infection should be evaluated clinically and serologically at 6, 12, 18, and 24 months after therapy. Those persons who meet the criteria for treatment failure (i.e., signs or symptoms that persist or recur or a sustained [>2 weeks] fourfold or greater increase in titer) should be managed in the same manner as persons without HIV (i.e., depending on history of sexual activity and on findings of neurologic examination, either repeat treatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks or CSF examination and repeat treatment guided by CSF findings) (see Latent Syphilis).
A majority of women will not achieve a fourfold decrease in titers before delivery, although this does not indicate treatment failure (645). However, a fourfold increase in titer after treatment (e.g., from 1:8 to 1:32) that is sustained for >2 weeks is concerning for reinfection or treatment failure. Nontreponemal titers can increase immediately after treatment, presumably related to the treatment response. Therefore, unless symptoms and signs exist of primary or secondary syphilis, follow-up titer should not be repeated until approximately 8 weeks after treatment. Inadequate maternal treatment is likely if delivery occurs within 30 days of therapy, clinical signs of infection are present at delivery, or the maternal antibody titer at delivery is fourfold higher than the pretreatment titer.
Notwithstanding the above findings, the literature on alcohol and REM sleep has some inconsistencies (Table 2). For example, a meta-analysis examined six studies that did not consider covariates and four studies that controlled for variables such as age and sex (all participants abstinent for at least 3 weeks). Even though the analyses among all subjects showed no differences in REM measured as the percentage of total sleep (REM%), the analyses did find increased REM% in persons with AUD compared to controls when controlling for some variables [26]. Other studies have found no difference in REM% between chronic alcohol users and normal controls in the second [106] and third [83] week of abstinence. Additionally, supporting the finding of no difference in REM between chronic alcohol users and controls, a study examining REM time after 4 weeks of abstinence found no difference between subjects with AUD and normal controls [183]. Another discrepancyappears in the form of a study that found REM% among participants with AUD to be reduced after 12 weeks of abstinence in comparison with REM% after 4 weeks of abstinence, arguing against a lasting REM rebound [171].
Similar to clinical studies examining sleep latency and SWS, REM sleep measurements appear to be important in clinical outcomes, but with conflicting results. The differences observed here might be consistent with the differences in the measurement of REM sleep in persons with AUD described above. For instance, while one study indicated a positive correlation between low REM% with response rate in a button-press task to obtain an alcoholic drink [8], Gillin et al. showed increased REM% and shorter REM latency upon admission and upon discharge from a four-week admission among relapsers in comparison with abstainers [82]. Another study showed that increased REM latency decreased the odds of relapsing [34], and one study found no connection between REM latency measured at 19 weeks of abstinence and subsequent relapse [69]. The variation in results regarding REM sleep may be due to the different effect that acute and chronic use, have on REM sleep, and be due to changes in REM sleep as the number of days abstinent increases. Another important consideration is that achieving long periods of abstinence (e.g., like 19 weeks) is in general a good predictor of abstinence and does so to a much greater degree than the predictive qualities of other physiological measurements obtained early in abstinence.
Studies indicate that most withdrawal symptoms occur during the first four weeks of stopping antipsychotic drugs.8 They often start one to four days after discontinuing medication and last up to six weeks, sometimes lessening during that period. Symptoms associated with cessation of quetiapine can include interruptions in sleep and insomnia, paresthesia (burning or prickling sensations), nausea, vomiting, diarrhea, dizziness, hypertension (high blood pressure), an increased heart rate, agitation, anxiety, sweating, anorexia, and myalgia. Though rare, movement disorders can emerge upon abrupt withdrawal of neuroleptic medications. Restlessness or hyperkinesia may last longer, sometimes months.6,7,25 2ff7e9595c
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