to treat tics or ocd in the absence of active infection. evidence for antibiotic treatment is inconclusive for pans, pandas, pitand and cans. murphy, kurlan and leckman (2010) said, "the use of prophylactic antibiotics to treat pandas has become widespread in the community, although the evidence supporting their use is equivocal." as of 2019, there is no evidence supporting the use rituximab or mycophenolate mofetil for treating pandas/pans. there is inconclusive evidence supporting immunomodulatory therapies (intravenous immunoglobulin (ivig) or therapeutic plasma exchange (tpe)) for pans and pandas; most studies have methodological issues. ivig was perceived as effective based on a self-reported survey. kalra and swedo wrote in 2009, "because ivig and plasma exchange both carry a substantial risk of adverse effects, use of these modalities should be reserved for children with particularly severe symptoms and a clear-cut pandas presentation." studies of experimental treatments for pans and pandas (ivig, tpe, antibiotics, tonsillectomy, corticosteroids and nsaids) are "few and in general have moderate or high risk of bias", according to a sigra et al review published in 2018, which states: nevertheless, there are 3 recent papers proposing guidelines for how to treat pandas and pans using psychiatric and behavioral interventions (thienemann et al., 2017), immunomodulatory therapies (frankovich et al., 2017) and antibiotics (cooperstock et al., 2017). these guidelines are proposed by a consortium of clinicians and researchers ... for children who fulfill criteria for pandas or pans. we believe that our results are in line with the proposed guidelines, and that the lack of evidence for treatment is based not on the inefficacy of the treatments, but on lack of systematic research.— sigra et al (2018) guidelines following a 2014 meeting in the us of swedo and physicians from stanford university, treatment guidelines for pans and pandas were published in 2017, in three parts. in a 2018 review, sigra et al said of the 2017 guidelines that treatment consensus was lacking and that results were inconclusive. a 2019 review by wilbur et al said that evidence for treatment of children with pandas/pans is lacking, and remission rates in symptoms after treatment "may represent the natural history of cases rather than true treatment effect". the wilbur et al 2019 review found no evidence to support tonsillectomy or prophylactic antibiotics, recommended standard approved therapies known to be effective for ocd, and cautioned against immunomodulatory therapies except in clinical trials. gilbert (2019) stated: "skeptics have concluded that treatment studies do not support antibiotic or immunomodulatory interventions for pandas. advocates published treatment guidelines supporting both." the guideline status in the uk is similar. the pandas and pans physicians network published guidelines in 2018 on a private healthcare platform, e-hospital. in april 2021, the british paediatric neurology association (bpna) issued a consensus statement with the child and adolescent psychiatry faculty of the royal college of psychiatrists stating that there is an absence of evidence for recommending immunomodulatory or prophylactic antibiotic treatments. this consensus statement was issued in place of a guideline as the authors stated that there was insufficient evidence for developing a typical guideline. it noted no previous guidelines for pandas existed or had been endorsed by official bodies in the uk, including the national institute for health and care excellence (nice), and that the 2018 guidelines available at a pandas/pans uk charity website and the private platform (e-hospital) had been developed independently of the bpna. similarly, the april 2021 treatment guidelines for nordic countries (denmark, norway, sweden and the uk) do not recommend tonsillectomy, antibiotic prophylaxis, or experimental immunomodulatory therapies outside of a specialist setting. a swedish review published in 2021 found a moderate potential for adverse effects, and a "very low certainty of evidence of beneficial effects", for treating individuals meeting the research definition of pans with antibiotics, anti-inflammatory medications, or immunomodulatory agents. the swedish review states that, "some researchers in the united states, on the basis of an assumption of an underlying neuroinflammation, recommend anti-inflammatory drugs, antibiotics and immunomodulatory treatment in the clinical management of these patients, swedish national guidelines imply that these treatments shall only be provided within the framework of research and development". the american academy of neurology 2011 guidelines say there are "inadequate data to determine the efficacy of plasmapheresis" and "insufficient evidence to support or refute the use of plasmapheresis", for treating ocd and tics "in the setting of pandas". the medical advisory board of the tourette syndrome association (now the tourette association of america) said in 2006, and reiterated in 2021: "treatment with antibiotics should not be initiated without clinical evidence of infection and a positive throat culture. experimental treatments based on the autoimmune theory, such as plasma exchange, immunoglobulin therapy, or prophylactic antibiotic treatment, should not be undertaken outside of formal clinical trials." the american heart association's 2009 guidelines state that they do "not recommend routine laboratory testing for gas to diagnose, long-term antistreptococcal prophylaxis to prevent, or immunoregulatory therapy (such as intravenous immunoglobulin, plasma exchange) to treat exacerbations of this disorder". society and culture the debate surrounding the pandas hypothesis has societal implications; the media and the internet have played a role in the pandas controversy. the news and other media report the difficulties of families who believe their children have pandas or pans. attempts to influence public policy have been advanced by advocacy networks such as the usa-based pandas network and canadian pandashelp. swerdlow (2005) summarized the societal implications of the hypothesis, and the role of the internet in the debate surrounding the pandas hypothesis: ... perhaps the most controversial putative ts trigger is exposure to streptococcal infections. the ubiquity of strep throats, the tremendous societal implications of over-treatment (e.g., antibiotic resistance or immunosuppressant side effects) versus medical implications of under-treatment (e.g., potentially irreversible autoimmune neurologic injury) are serious matters. with the level of desperation among internet-armed parents, this controversy has sparked contentious disagreements, too often lacking both objectivity and civility. murphy, kurlan and leckman (2010) discussed the influence of the media and the internet in a paper that proposed a "way forward" with the "group of disorders collectively described as pandas":of concern, public awareness has outpaced our scientific knowledge base, with multiple magazine and newspaper articles and internet chat rooms calling this issue to the public's attention. compared with ~ 200 reports listed on medline—many involving a single patient, and others reporting the same patients in different papers, with most of these reporting on subjects who do not meet the current pandas criteria—there are over 100,000 sites on the internet where the possible streptococcus–ocd–td relationship is discussed. this gap between public interest in pandas and conclusive evidence supporting this link calls for increased scientific attention to the relationship between gas and ocd/tics, particularly examining basic underlying cellular and immune mechanisms. history pandas was first described in 1998 by susan swedo and a group of researchers at the us national institute of mental health (a branch of the nih). a similar clinical picture was proposed for pitands (pediatric infection-triggered autoimmune neuropsychiatric disorders) for those who met the swedo et al criteria for pandas, but with symptoms triggered by an infection other than gas. michael pichichero (2009) noted several reasons that pandas had not been validated as a disease classification. its proposed age of onset and clinical features reflected a particular group of patients chosen for research studies, with no systematic studies of the possible relationship of gas to other neurologic symptoms. there was dispute over whether its symptom of choreiform movements was distinct from the similar movements of sc. it was not known whether the pattern of abrupt onset was specific to pandas. finally, there was controversy over whether a temporal relationship between gas infections and pandas symptoms existed. in light of controversies in establishing a basis for the hypothesis, a 2010 paper calling for "a way forward", murphy, kurlan and leckman said: "it is time for the national institutes of health, in combination with advocacy and professional organizations, to convene a panel of experts not to debate the current data, but to chart a way forward. for now we have only to offer our standard therapies in treating ocd and tics, but one day we may have evidence that also allows us to add antibiotics or other immune-specific treatments to our armamentarium." a 2011 paper by singer proposed cans, childhood acute neuropsychiatric symptoms—a new, "broader concept" in favor or requiring only acute-onset. cans removes the requirement for gas infection, allowing for multiple causes, which singer proposed because of the "inconclusive and conflicting scientific support" for pandas, including "strong evidence suggesting the absence of an important role for gabhs, a failure to apply published criteria, and a lack of scientific support for proposed therapies". by 2012, with limitations of the pandas hypothesis published, the broader pediatric acute-onset neuropsychiatric syndrome (pans) was proposed (also by swedo and colleagues, following a conference) to create a better defined condition for research purposes. it describes individuals with eating disorders or rapid onset of ocd along with other neuropsychiatric symptoms, and postulates that the causes can be other than gas. the term pediatric was chosen over childhood because some cases described at the conference included adolescents. whether the pans hypothesis defines a distinct entity is unclear as of 2019. swedo retired from the nih in 2019, but serves on the scientific advisory board of the pandas physician network. as of 2020, the nih information pages (which swedo helped write) do not mention the studies that do not support the pandas hypothesis.