WEBVTT 00:00:06.859 --> 00:00:10.379 Good evening. 00:00:10.380 --> 00:00:13.410 thank you no doubt for 00:00:13.410 --> 00:00:17.119 Thank you Nora, for making possible this's evening's 00:00:17.119 --> 00:00:20.560 hopefully dialogue. Chronic fatigue syndrome 00:00:20.560 --> 00:00:23.660 is arguably one of the most 00:00:23.660 --> 00:00:27.519 controverted, misunderstood, misperceived 00:00:27.519 --> 00:00:32.119 fields in medicine today. Although 00:00:32.119 --> 00:00:36.550 it is clear that the health of millions of people 00:00:36.550 --> 00:00:40.700 has been compromised significantly by this disease, 00:00:40.700 --> 00:00:44.510 still, in medicine, we face situations 00:00:44.510 --> 00:00:49.190 where an extreme, even in our own medical community-- 00:00:49.190 --> 00:00:52.190 the diseased is not believed, that it is real. 00:00:52.190 --> 00:00:56.180 Which is a shame. So the one thing, if there is one thing 00:00:56.180 --> 00:01:00.260 of anyone in this audience here today, that I would like to 00:01:00.260 --> 00:01:05.890 have us a point to take home, of your family members, your friends, or yourself, 00:01:05.890 --> 00:01:09.880 is to not kid yourself--this is a real disease. 00:01:09.880 --> 00:01:13.920 And what I would like to do tonight is share with you 00:01:13.920 --> 00:01:17.400 the evolving understanding 00:01:17.400 --> 00:01:22.119 that here at Stanford we have put together. What we tell you today 00:01:22.119 --> 00:01:26.100 may not be true tomorrow, but what we tell you today 00:01:26.100 --> 00:01:30.530 hopefully is better than what we had as a model or as an understanding 00:01:30.530 --> 00:01:34.200 yesterday. And it is evolving. It's changing. 00:01:34.200 --> 00:01:37.289 But we have a simple goal, is--one day, 00:01:37.290 --> 00:01:41.360 one day, have CFS, 00:01:41.360 --> 00:01:46.600 a history of the past, so we do one day be able 00:01:46.600 --> 00:01:51.619 to conquer the disease, and be able to bring relief finally to the many patients 00:01:51.619 --> 00:01:52.450 who are suffering. 00:01:52.450 --> 00:01:56.390 I do not have the time frame for this, but trust me, 00:01:56.390 --> 00:01:59.600 we are working hard in making that time frame 00:01:59.600 --> 00:02:03.119 the shortest possible. Allow me to start the 00:02:03.119 --> 00:02:06.549 presentation with a real case. This is a patient-- 00:02:06.549 --> 00:02:11.540 I don't know if she's in the audience or not--but it's a 53-year-old woman 00:02:11.540 --> 00:02:14.709 who came to see us in 2008 00:02:14.709 --> 00:02:18.150 because she had had disabling fatigue 00:22:44.990 --> 00:22:48.400 of treatment. And what they found, if they gave 00:22:48.400 --> 00:22:52.220 the drug or placebo--so they would randomize to drug 00:22:52.220 --> 00:22:56.100 for month-and-a-half, or placebo for month-and-a-half, 00:22:56.100 --> 00:22:59.209 what they found is that there was no difference. But just 00:22:59.210 --> 00:23:03.100 put that in the in the back of your brain. The fact 00:23:03.100 --> 00:23:06.230 that that patient, those patients, got a month-and-a-half 00:23:06.230 --> 00:23:09.669 of antiviral treatment, or acyclovir. 00:23:09.669 --> 00:23:13.340 So the one thing that we changed at Stanford about 00:23:13.340 --> 00:23:17.100 seven years ago, was that we 00:23:17.100 --> 00:23:20.450 brought a new model. And we 00:23:20.450 --> 00:23:24.679 thought if the patients have been here for a long period of time, 00:23:24.679 --> 00:23:29.000 and if it's possible that an infectious agent is behind the symptoms 00:23:29.000 --> 00:23:32.120 at a chronic level, will it be possible that 00:23:32.120 --> 00:23:36.350 if we intervene with the appropriate agent--and finding that appropriate agent 00:23:36.350 --> 00:23:37.309 may be a really 00:23:37.309 --> 00:23:41.710 daunting task--is it possible that then long-term, 00:23:41.710 --> 00:23:46.409 with appropriate anti-microbial interventions, can improve the symptoms 00:23:46.409 --> 00:23:50.330 in subsets of patients, not to repeat the mistakes of the past, 00:23:50.330 --> 00:23:54.350 of treating all the patients as the same homogeneous group. 00:23:54.350 --> 00:23:57.658 And to our surprise, when we took patients and-- 00:23:57.659 --> 00:24:00.890 it's beyond the scope of tonight's conversation on how we 00:24:00.890 --> 00:24:06.260 ran into this surgroup--we found that if patients had high levels 00:24:06.260 --> 00:24:10.720 of antibodies against Epstein-Barr virus, the same virus that has been 00:24:10.720 --> 00:24:14.870 clearly tied to the onset of CFS, and another virus 00:24:14.870 --> 00:24:18.600 called Human Herpesvirus-6, if they have high levels against 00:24:18.600 --> 00:24:21.830 those two viruses, it looks like when we gave them 00:24:21.830 --> 00:24:25.210 another drug called Valganciclovir 00:24:25.210 --> 00:24:28.409 for six months in this abscissa. You have 00:24:28.409 --> 00:24:33.320 a year's, so goes all the way to six months, half a year here, 00:24:33.320 --> 00:24:37.830 and in the same abscissa, but for when the patients were starting before therapy, 00:24:37.830 --> 00:24:41.600 you have all the way up to twenty years. So the patient may have been sick for 00:24:41.600 --> 00:24:42.379 eighteen years, 00:24:42.380 --> 00:24:46.460 one year, five years--no matter how long they were sick 00:24:46.460 --> 00:24:49.580 when we gave this drug for six months, 00:24:49.580 --> 00:24:54.490 total surprise to us. They had this remarkable 00:24:54.490 --> 00:24:58.529 improvement in their physical and cognitive 00:24:58.529 --> 00:25:03.900 function. And to our surprise as well, 00:25:03.900 --> 00:25:06.279 the initial reaction to 00:25:06.279 --> 00:25:13.210 them was, they got worse. And then they improved. 00:25:13.210 --> 00:25:17.320 The worsening was a complete surprise to us. And we made a mistake initially 00:25:17.320 --> 00:25:21.879 because we let people believe that for patients to get 00:25:21.880 --> 00:25:25.529 better with this intervention who had these markers in the blood, 00:25:25.529 --> 00:25:29.800 they had to get worse. And that later on 00:25:29.800 --> 00:25:32.600 turns out to be not correct. There are patients who can get better 00:25:32.600 --> 00:25:36.340 without significant worsening, but still we see patients who get worse 00:25:36.340 --> 00:25:40.490 with the initial treatment. Now, we cannot 00:25:40.490 --> 00:25:45.200 be certain that this would have not been done because we perhaps 00:25:45.200 --> 00:25:46.529 validated the patients; we 00:25:46.529 --> 00:25:50.580 listened to them, so that we were doing a placebo effect. 00:25:50.580 --> 00:25:54.370 It's hard to argue that this is placebo when somebody has been sick for 00:25:54.370 --> 00:25:55.449 twenty years, 00:25:55.450 --> 00:25:59.900 or eighty years, they get an intervention for six months, and they suddenly get better. 00:25:59.900 --> 00:26:03.290 But granted, we have to go to what is called a 00:26:03.290 --> 00:26:06.450 randomized, placebo-controlled double-blind 00:26:06.450 --> 00:26:10.460 pilot study, to see if we could give the drug 00:26:10.460 --> 00:26:14.279 to patients when they didn't know they were getting the drug, 00:26:14.279 --> 00:26:17.330 or the sugar pill, and we the physicians 00:26:17.330 --> 00:26:20.490 will not know the same thing. So: double-blind. 00:26:20.490 --> 00:26:25.000 And we were fortunate to have the sponsorship. 00:26:25.000 --> 00:26:28.840 The answer for many of the questions we face 00:26:28.840 --> 00:26:32.539 with chronic fatigue syndrome is doing clinical trials, but those are 00:26:32.539 --> 00:26:35.890 very expensive things to do, enterprises to do, 00:26:35.890 --> 00:26:39.779 and we were lucky that we had the sponsorship from the manufacturer 00:26:39.779 --> 00:26:42.919 of the drug in this case. Like any 00:26:42.919 --> 00:26:46.980 intervention, we do need a team. 00:26:46.980 --> 00:26:50.750 Nothing can happen these days in research without having 00:26:50.750 --> 00:26:54.210 an outstanding team. And what we did is 00:26:54.210 --> 00:26:58.440 randomized the patients to two areas: to either placebo, 00:26:58.440 --> 00:27:02.270 sugar pill, or valacyclovir for six months, 00:27:02.270 --> 00:27:06.200 and then for three months we stayed blind still. 00:27:06.200 --> 00:27:10.220 At nine months, we took the data, put it in 00:27:10.220 --> 00:27:13.610 three CVs, shipped it to three different, 00:27:13.610 --> 00:27:17.209 three different places, so that nobody could touch the data 00:27:17.210 --> 00:27:20.210 after the blind code was broken, 00:27:20.210 --> 00:27:23.529 and then we broke the code and see how the patients did 00:27:23.529 --> 00:27:27.390 on the drug versus the sugar pill. 00:27:27.390 --> 00:27:31.260 This is a graph that shows what happened 00:27:31.260 --> 00:27:34.710 to the patients who are either on the 00:27:34.710 --> 00:27:39.289 placebo in red, or who are on the treatment 00:27:39.289 --> 00:27:42.460 in green. And in this scale, 00:27:42.460 --> 00:27:46.230 going down means you are getting better. 00:27:46.230 --> 00:27:49.270 So the patient who went on the treatment went down, 00:27:49.270 --> 00:27:52.360 meaning they got better, and that 00:27:52.360 --> 00:27:55.459 trend of going down was 00:27:55.460 --> 00:27:59.110 according to this statistical model, it's statistically significantly 00:27:59.110 --> 00:28:02.990 different than those in the placebo, suggesting here 00:28:02.990 --> 00:28:07.190 that the benefit that we have shown before, when we were giving this drug to 00:28:07.190 --> 00:28:08.149 patients, 00:28:08.149 --> 00:28:12.120 is mediated by something that the drug is doing, and not something that they 00:28:12.120 --> 00:28:12.870 are doing 00:28:12.870 --> 00:28:18.800 themselves through placebo. We also assessed 00:28:18.800 --> 00:28:22.189 their cognitive function, meaning we asked the patients 00:28:22.190 --> 00:28:26.290 how they felt in terms of their cognitive performance. 00:28:26.290 --> 00:28:29.720 And they say, I feel 100 percent, which no one will tell us 00:28:29.720 --> 00:28:33.429 when they were sick, or they will say 10 percent or 50 percent and so forth. 00:28:33.429 --> 00:28:37.820 That is very hard to correlate, because it also depends on how 00:28:37.820 --> 00:28:41.408 good their sleep (is) or what other medications they are taking. 00:28:41.409 --> 00:28:44.630 et cetera. So when we looked at 00:28:44.630 --> 00:28:47.909 what happened with their cognitive function--self-reported, 00:28:47.909 --> 00:28:51.110 but remember, under double-blind conditions, not knowing if they were 00:28:51.110 --> 00:28:52.600 getting treatment or placebo-- 00:28:52.600 --> 00:28:56.779 the trajectory also for those who went into treatment 00:28:56.779 --> 00:29:00.510 was better that those who were in the placebo. 00:29:00.510 --> 00:29:03.669 Now is one of those things-- 00:29:03.669 --> 00:29:09.120 the research--never stops either surprising you or fascinating you. 00:29:09.120 --> 00:29:13.610 The randomization for this study, meaning we allocated the patients 00:29:13.610 --> 00:29:17.729 to either group by pure chance-- 00:29:17.730 --> 00:29:20.760 the allocation of the patients to the two groups 00:29:20.760 --> 00:29:25.158 was done by somebody in Geneva, in Europe. So we will see a patient 00:29:25.159 --> 00:29:28.419 and we'll say, "That patient is a candidate for the study." 00:29:28.419 --> 00:29:32.710 We didn't allocate them to one group or the other. We will call Geneva, to a 00:29:32.710 --> 00:29:33.679 group there, 00:29:33.679 --> 00:29:36.929 and they would give us the answer the next day, or whatever time difference it was, 00:29:37.299 --> 00:29:41.220 and they would tell us, "This is the group the patient should go, group X." 00:29:41.220 --> 00:29:44.299 And they would call pharmacy and they would give us the appeals for that 00:29:44.299 --> 00:29:48.360 patient and so forth. Yet, despite that it was 00:29:48.360 --> 00:29:52.290 totally by chance and by pure randomization, 00:29:52.290 --> 00:29:55.279 if you'll notice, here, the baseline 00:29:55.279 --> 00:30:00.590 levels of cognitive function for the treatment group is slightly lower 00:30:00.590 --> 00:30:04.370 than the placebo. We were fortunate that that this was not statistically 00:30:04.370 --> 00:30:09.490 significant, but the patients in the treatment group started with a slight 00:30:09.490 --> 00:30:10.800 disadvantage 00:30:10.800 --> 00:30:14.340 over the placebo. And the same thing actually was for the fatigue. 00:30:14.340 --> 00:30:19.800 Remember that in this scale, I mentioned to you that the higher the worse, 00:30:19.800 --> 00:30:22.199 and again, the patients, 00:30:22.200 --> 00:30:25.559 well in this case, you know, the lower is the better, so the treatment is 00:30:25.559 --> 00:30:27.928 started at the right place. 00:30:27.929 --> 00:30:32.279 And then the other aspect that we did was to see how the cognitive did by 00:30:32.279 --> 00:30:35.659 a questioner. So the previous light was how they did 00:30:35.659 --> 00:30:39.290 with self-reported cognitive function; this is how they do 00:30:39.290 --> 00:30:42.500 with a questioner that assesses their mental capacity, 00:30:42.500 --> 00:30:46.289 and in this case, going down again is improving 00:30:46.289 --> 00:30:50.210 and again the treatment group is slightly worse 00:30:50.210 --> 00:30:53.419 than the starting place for the placebo, 00:30:53.419 --> 00:30:56.570 yet the trajectory of the treatment group 00:30:56.570 --> 00:31:00.279 is statistically significantly better--going down it's better-- 00:31:00.279 --> 00:31:03.440 than the placebo group. So in this study we 00:31:03.440 --> 00:31:06.630 offer perhaps what are the first 00:31:06.630 --> 00:31:11.290 evidences that if you intervene with an appropriate drug, 00:31:11.290 --> 00:31:14.110 with a specific biomarker in black like titers 00:31:14.110 --> 00:31:18.299 elevated against those two viruses, it appears that we can make 00:31:18.299 --> 00:31:21.559 a significant difference in these patients' physical 00:31:21.559 --> 00:31:26.590 and cognitive status, independent of placebo. 00:31:26.590 --> 00:31:29.809 We were not just happy with 00:31:29.809 --> 00:31:34.570 just seeing this and not being able to explain it. We wanted to go beyond that. 00:31:34.570 --> 00:31:37.970 And we have noticed that in patients who received the drug, 00:31:37.970 --> 00:31:42.710 these cells, called neutrophils, increase in a statistical manner, 00:31:42.710 --> 00:31:46.700 that is not seen in the patients who get placebo. 00:31:46.700 --> 00:31:50.210 So something is associated with neutrophils that 00:31:50.210 --> 00:31:55.299 maybe, maybe, (is) one potential explanation of why they get better. 00:31:55.299 --> 00:31:58.710 The other cells that change 00:31:58.710 --> 00:32:03.200 are the monocytes, in this case they go down in the patients who get the drug, 00:32:03.200 --> 00:32:07.500 and not in those who get the placebo. At at the same time, 00:32:07.500 --> 00:32:10.669 we took the serum of these patients, and through a 00:32:10.669 --> 00:32:14.720 technology that is available here at Stanford, and in collaboration 00:32:14.720 --> 00:32:18.909 with our colleagues in the immunology department, we were able to measure 00:32:18.909 --> 00:32:22.529 through this technique that is called Luminex technology, where you can 00:32:22.529 --> 00:32:27.429 measure a hundred cytokines, a hundred analytes, in a single well 00:32:27.429 --> 00:32:31.549 of a single patient at the same time, we were able to measure what we call 00:32:31.549 --> 00:32:33.820 cytokines. Cytokines are molecules 00:32:33.820 --> 00:32:37.290 that the immune system uses to talk from one cell 00:32:37.290 --> 00:32:41.110 to the other. And through this technology we were able to show 00:32:41.110 --> 00:32:45.769 that in those patients at baseline that I show you that they were slightly worse 00:32:45.769 --> 00:32:50.500 for the treatment group, we show that the certain cytokines were higher 00:32:50.500 --> 00:32:53.830 in those who were worse, than in those who were better--initially, 00:32:53.830 --> 00:32:57.720 like IL5 and IL17. And more importantly, 00:32:57.720 --> 00:33:01.169 over time, the patients on the treatment, 00:33:01.169 --> 00:33:04.210 on the Valganciclovir, on the drug, have 00:33:04.210 --> 00:33:07.500 elevation in cytokines that were not seen 00:33:07.500 --> 00:33:10.980 as much in the patient in the placebo. Cytokines like 00:33:10.980 --> 00:33:16.100 IL5, IL17, cytokines that attract neutrophils--the same cell 00:33:16.100 --> 00:33:20.689 that I mentioned to you that is elevated. Or cytokines that had to do 00:33:20.690 --> 00:33:24.330 with monocyte communication, the same cell that I mentioned to you 00:33:24.330 --> 00:33:27.539 that it goes down. And the drug was safe 00:33:27.539 --> 00:33:31.679 during the period of administration. And we concluded then 00:33:31.679 --> 00:33:35.220 that if the patients have high levels of these antibodies against 00:33:35.220 --> 00:33:38.279 HHV-6 and DBV, giving them 00:33:38.279 --> 00:33:41.740 Valganciclovir for six months 00:33:41.740 --> 00:33:45.240 appears to correlate with an improvement in cognitive and physical 00:33:45.240 --> 00:33:48.620 that is independent from placebo and we have 00:33:48.620 --> 00:33:52.510 a mechanism, proposed a mechanism 00:33:52.510 --> 00:33:57.440 through immunomodulation, meaning that sometime the drugs work; 00:33:57.440 --> 00:34:00.940 not necessarily through the fact that they are killing the organism, 00:34:00.940 --> 00:34:05.590 but by the fact that they are making the immune system (go) one direction 00:34:05.590 --> 00:34:08.918 that is beneficial to the patient. So... 00:34:08.918 --> 00:34:11.960 But I want to emphasize two things. 00:34:11.960 --> 00:34:16.699 Not all the patients have those blood markers. So not everybody will be 00:34:16.699 --> 00:34:20.109 in theory a candidate for that intervention. And unfortunately, not 00:34:20.109 --> 00:34:24.848 all the patients with the markers necessarily improve. 00:34:24.849 --> 00:34:27.969 so that let us, or has led us, 00:34:27.969 --> 00:34:31.290 at Stanford to identify what we call 00:34:31.300 --> 00:34:35.440 sub-groups of patients with CFS, those who 00:34:35.440 --> 00:34:38.829 meet that profile of the HSV-6, EBV, 00:34:38.829 --> 00:34:43.210 we have found other patients that have what we call the herpes simplex one 00:34:43.210 --> 00:34:46.349 or two sub-group. Patients who 00:34:46.349 --> 00:34:49.800 absolutely tell you that their CFS worsened 00:34:49.800 --> 00:34:53.149 when their oral herpes, the famous 00:34:53.149 --> 00:34:57.250 fever blisters, the oral blisters, or genital herpes, 00:34:57.250 --> 00:35:00.329 that when those exacerbate, 00:35:00.329 --> 00:35:03.970 and manifest in the way of painful lesions, those patients 00:35:03.970 --> 00:35:07.780 actually, their symptoms get much more worse, 00:35:07.790 --> 00:35:11.000 or that their disease began when they have the outbreak, the first outbreak 00:35:11.000 --> 00:35:14.100 with one of those two viruses. So that's what we have called a 00:35:14.100 --> 00:35:17.349 herpes simplex sub-group. We have had some Brucella 00:35:17.349 --> 00:35:20.940 patients, others with Q fever, like the ones that they 00:35:20.940 --> 00:35:24.890 found in Australia, mycoplasma, chlamydia, 00:35:24.890 --> 00:35:27.570 and we have found patients who have low titers 00:35:27.570 --> 00:35:30.820 against HSV-6, but have very high levels 00:35:30.820 --> 00:35:34.130 of this HSV-6 virus that 00:35:34.130 --> 00:35:38.619 have also clearly been associated with significant fatigue in these patients, 00:35:38.619 --> 00:35:41.859 and those patients are the ones that we call chromosomally 00:35:41.859 --> 00:35:45.420 integrated human herpes virus six. So this is another 00:35:45.420 --> 00:35:49.910 completely different sub-group. And it's a tougher group 00:35:49.910 --> 00:35:54.490 to treat. I'm sure you remember the first patient that I 00:35:54.500 --> 00:35:58.530 told you. The 50 year-old woman who came in 2008 00:35:58.530 --> 00:36:02.760 to see us, with the hope that we could find something, 00:36:02.760 --> 00:36:06.710 and we did all these titers, and they were low, or negative, 00:36:06.710 --> 00:36:10.900 but she's one of the patients who was found to have very high levels 00:36:10.900 --> 00:36:14.800 of the human herpes virus 6 in her blood. She one of the patients 00:36:14.800 --> 00:36:18.510 that we call, that the virus has found at clever way 00:36:18.510 --> 00:36:22.520 to get into the actual genome, into the genetic material 00:36:22.520 --> 00:36:26.900 of her own cells, in a clever way to hide, 00:36:26.100 --> 00:36:30.640 and to perhaps to produce the damage. So the patient that I mentioned to you 00:36:30.640 --> 00:36:35.520 in 2008, we were studying her--and this is a way to measure 00:36:35.520 --> 00:36:39.200 her fatigue and her cognitive abilities. 00:36:39.200 --> 00:36:42.300 Being 100 is being in complete misery. 00:36:42.300 --> 00:36:46.740 It's really being sick. The CDC has done studies with this questionnaire 00:36:46.740 --> 00:36:50.598 for physical and cognitive dysfunction. Most of the CFS patients 00:36:50.599 --> 00:36:53.920 are around 60. Being completely well 00:36:53.920 --> 00:36:57.760 is around 10. So if you are (a) 60, you are really sick. 00:36:57.760 --> 00:37:00.940 She was around (an) 80. This is the same woman, 00:37:00.940 --> 00:37:05.609 patient, wife, mother, that I talked to you at the beginning. 00:37:05.609 --> 00:37:09.890 We started with the antiviral, and you can see how 00:37:09.890 --> 00:37:13.150 by different antivirual interventions of certain kinds, 00:37:13.150 --> 00:37:16.599 finally she has some relief here. Where 00:37:16.599 --> 00:37:19.670 her level of function going from 80 00:37:19.670 --> 00:37:24.210 to almost 25 is significantly improved. 00:37:24.210 --> 00:37:27.290 She went from not been able to run errands, 00:37:27.290 --> 00:37:31.990 to now go out, and travel, and enjoy the graduation of her 00:37:31.990 --> 00:37:35.959 daughter, et cetera, et cetera. However, those drugs, 00:37:35.960 --> 00:37:39.000 for us to be able to achieve this resolution 00:37:39.000 --> 00:37:42.640 we had to give them at very high doses, and you can only go 00:37:42.640 --> 00:37:46.859 with this drug so long. So we have to move her to other medications that are not 00:37:46.859 --> 00:37:47.640 so effective. 00:37:47.640 --> 00:37:51.250 And unfortunately she has relapsed recently. 00:37:51.250 --> 00:37:55.740 For her, we're going to try hopefully a clever way 00:37:55.740 --> 00:37:59.310 to measure what is in her blood that changes that makes her feel 00:37:59.310 --> 00:38:02.660 so much better, going from 80 which is 00:38:02.660 --> 00:38:06.240 near hell, to around 20 which is near 00:38:06.240 --> 00:38:09.490 health. So hopefully we'll be able to 00:38:09.490 --> 00:38:13.649 achieve that, but I just want to show you this as an example 00:38:13.650 --> 00:38:17.339 that there is something there that we can improve. 00:38:17.339 --> 00:38:20.940 All we have to do is devote resources and more people 00:38:20.940 --> 00:38:24.430 to be able to unveil this mystery. 00:38:24.430 --> 00:38:27.759 So that has been, so far, our experience. 00:38:27.760 --> 00:38:31.760 I would like to mention two things quickly because I'm sure you have 00:38:31.760 --> 00:38:33.500 questions about it. 00:38:33.500 --> 00:38:36.810 It is what recently has been reported as the famous 00:38:36.810 --> 00:38:40.560 XMRV virus. The XMRV virus 00:38:40.560 --> 00:38:44.770 was--that, and the Lancet study about degraded 00:38:44.770 --> 00:38:47.890 exercise. So I'm going to comment on those two things, because they are very 00:38:47.890 --> 00:38:52.420 timely. So the XMRV is a virus that was found 00:38:52.420 --> 00:38:56.480 in prostatic tumors, and it was thought that it could be associated with 00:38:56.480 --> 00:39:00.750 prostatic cancer. But then the surprise came in 2009 00:39:00.750 --> 00:39:04.550 when it was reported by a group from Nevada that patients with 00:39:04.550 --> 00:39:10.490 the disease had 70 percent--it's 67 percent, but you can't remember a 70 percent-- 00:39:10.490 --> 00:39:14.720 the CFS patient had the virus. Well yes, only four percent 00:39:14.720 --> 00:39:18.310 of healthy controls had it. So that caused a major splash 00:39:18.310 --> 00:39:21.570 and hope of the possibility that this agent 00:39:21.570 --> 00:39:25.470 could be behind, also, in addition to the other ones that I showed you, 00:39:25.470 --> 00:39:29.629 and in addition to the ones that we are going after at Stanford. 00:39:29.630 --> 00:39:33.700 The problem has been, that following that study, 00:39:33.700 --> 00:39:37.109 there have been two others supporting those findings 00:39:37.109 --> 00:39:41.600 and about six others that show that the association 00:39:41.600 --> 00:39:47.359 is not there. So there is one, this is one study from the U.S., the 70 percent 00:39:47.359 --> 00:39:50.730 versus the four percent that I mentioned to you 00:39:50.730 --> 00:39:55.630 that have the 70 percent in the patients versus four percent in the controls. 00:39:55.630 --> 00:39:59.119 The other study that was positive is a study from Boston 00:39:59.119 --> 00:40:03.420 when it was not 70 percent, it was almost 87 percent, 00:40:03.420 --> 00:40:06.520 and in controls it was about 7 percent. 00:40:06.520 --> 00:40:10.509 All the other studies, all the studies in Europe have been negative; 00:40:10.510 --> 00:40:15.210 the other studies, other than those two in the United States, have been negative, 00:40:15.210 --> 00:40:21.329 except one small one that has not been fully reported that was also positive from New York City. 00:40:21.329 --> 00:40:25.450 so it is a mystery, it's a challenge, it's a controversy, 00:40:25.450 --> 00:40:28.649 and we just have to step up to the challenge and solve it 00:40:28.650 --> 00:40:33.500 for the patients and not shy away and not take a position 00:40:33.500 --> 00:40:36.970 he has been really disappointing to me to see how 00:40:36.970 --> 00:40:40.930 colleagues who do not find the same thing that others do 00:40:40.930 --> 00:40:44.910 step up to the podium and said, "The other findings are wrong; 00:40:44.910 --> 00:40:49.200 we find the truth," et cetera. We are not going to be able able to solve this disease 00:40:49.200 --> 00:40:53.390 through taking dogmatic positions like this. So it is controversial 00:40:53.390 --> 00:40:56.910 but no group has produced proof 00:40:56.910 --> 00:41:01.180 that the association is there; nor any group has produced proof 00:41:01.180 --> 00:41:06.210 that it's not there. The retroviruses--this is a retrovirus-- 00:41:06.210 --> 00:41:09.839 they have a great capacity to hide and to do 00:41:09.839 --> 00:41:13.910 bad things, either in a long period of range 00:41:13.910 --> 00:41:17.700 or very short. It's the same group with the HIV virus 00:41:17.700 --> 00:41:21.210 but it's not HIV. A kind of 00:41:21.210 --> 00:41:25.500 unique life cycle where they can get very cleverly 00:41:25.500 --> 00:41:28.960 inside the cell and they can integrate into the human 00:41:28.960 --> 00:41:32.000 genetic material, hence their ability to hide 00:41:32.000 --> 00:41:35.700 and to cause, in a very sneaky way, 00:41:35.700 --> 00:41:39.359 disease (in) us. There are several kinds; 00:41:39.359 --> 00:41:44.600 this XMRV virus came from mice--no question about it-- 00:41:44.600 --> 00:41:48.890 and some of those viruses have mutated to the point that they are only 00:41:48.890 --> 00:41:49.819 able to stay in humans; 00:41:49.819 --> 00:41:53.190 there are others that can be in mice and humans, 00:41:53.190 --> 00:41:57.109 and there are others that cannot be in humans. So there are different kinds, 00:41:57.109 --> 00:42:00.609 but the reality is that the question is out there 00:42:00.609 --> 00:42:04.339 and it needs to be solved. And we as America 00:42:04.339 --> 00:42:07.640 and the scientific community need to step up and 00:42:07.640 --> 00:42:12.569 solve the mystery. There are different ways to measure the virus, so that's 00:42:12.569 --> 00:42:16.740 possibly part of the problem. There are ways to measure the actual virus; 00:42:16.740 --> 00:42:20.848 with measuring the nuclear acid to look at the proteins, 00:42:20.849 --> 00:42:23.990 to look at the cultural dividers, to look at 00:42:23.990 --> 00:42:29.740 how the antibody responds in humans to the virus, as a way to detect the virus-- 00:42:29.740 --> 00:42:33.439 So there are different methods that make it a little bit more difficult, but not 00:42:33.440 --> 00:42:37.530 impossible, to understand what is happening. Also, 00:42:37.530 --> 00:42:40.890 people, or different laboratories, using different 00:42:40.890 --> 00:42:44.348 reagents; they use different 00:42:44.349 --> 00:42:49.329 positive or negative controls; the virus appears to be in very small amounts, 00:42:49.329 --> 00:42:52.990 so that makes it hard for people to find it. 00:42:52.990 --> 00:42:57.959 And also, the studies come from different geographical areas. 00:42:57.960 --> 00:43:01.100 Infectious diseases is characterized by this. 00:43:01.100 --> 00:43:05.900 There are infections that present only in the United States and ever seen in Europe. 00:43:05.900 --> 00:43:10.569 There are infections that are only seen in Latin America, never seen outside 00:43:10.569 --> 00:43:14.170 the Americas. So this is not news-- 00:43:14.170 --> 00:43:17.290 that an infectious agent could be restricted to certain geographical 00:43:17.290 --> 00:43:21.890 locales, and it could be the case in this situation as well. 00:43:21.890 --> 00:43:25.200 So what is the bottom line? What is the bottom line with this 00:43:25.200 --> 00:43:28.609 XMRV virus? It can be present 00:43:28.609 --> 00:43:33.310 in people who have no disease. And it could be, according to the study so far 00:43:33.310 --> 00:43:37.650 up to seven percent. It can be present in patients with prostate cancer: 00:43:37.650 --> 00:43:41.750 up to 27 percent. It can can be present in patients with CFS: 00:43:41.750 --> 00:43:47.230 up to 87 percent. All the European studies have been negative so far. 00:43:47.230 --> 00:43:51.390 In the study from Boston, there were patients who were positive 00:43:51.390 --> 00:43:54.480 in blood samples that had been taken fifty years 00:43:54.480 --> 00:43:58.390 ago--they went to those patients again, they got blood again, and they were 00:43:58.390 --> 00:43:59.710 positive again. 00:43:59.710 --> 00:44:02.780 so we know that the virus can be there 00:44:02.780 --> 00:44:06.890 for long periods of time. And obviously 00:44:06.890 --> 00:44:09.520 we need to have the right studies 00:44:09.520 --> 00:44:13.670 in a smart way and we are fortunate, the Stanford group is fortunate, 00:44:13.670 --> 00:44:18.000 to be associated now with a group at Columbia 00:44:18.000 --> 00:44:22.990 with directions, and the directions of the NIH, to hopefully be able 00:44:22.990 --> 00:44:25.220 to provide the right kind of data that will help 00:44:25.220 --> 00:44:29.578 to support one way or the other. And another possibility 00:44:29.579 --> 00:44:34.130 is to do a specific intervention, because the drugs that work against a virus 00:44:34.130 --> 00:44:38.490 are very specific. In the next few minutes, 00:44:38.490 --> 00:44:44.149 I would like to share with you how at Stanford we have tried to put this together 00:44:44.150 --> 00:44:47.680 as a model of pathogenesis of this disease. 00:44:47.680 --> 00:44:52.180 So as I told you before, it is known that some patients start with infection 00:44:52.180 --> 00:44:55.440 and that the more severe the infection at the beginning, 00:44:55.440 --> 00:44:59.290 the higher is the chance that they go into chronic fatigue syndrome. 00:44:59.290 --> 00:45:03.690 Most of the infections that have associated with 00:45:03.690 --> 00:45:07.180 chronic fatigue syndrome are intracellular: they hide 00:45:07.180 --> 00:45:11.328 inside the cell. They like to go to the brain; 00:45:11.329 --> 00:45:15.230 they like to go to the lymph nodes. So I think that they are telling us something 00:45:15.230 --> 00:45:19.390 there from a mechanistic point of view. Several 00:45:19.390 --> 00:45:22.720 infections can do the same thing; they can 00:45:22.720 --> 00:45:26.189 trigger CFS. I think that this is telling us 00:45:26.190 --> 00:45:29.190 that what is most likely responsible for 00:45:29.190 --> 00:45:33.490 the problem it's not the organism itself attacking the patient, but it's the 00:45:33.490 --> 00:45:35.980 immune response to them. 00:45:35.990 --> 00:45:38.500 Several of them can do it; the severe ones seem to be 00:45:38.500 --> 00:45:43.140 doing it more successfully, so it's likely that is the immune response against them 00:45:43.140 --> 00:45:46.339 what is doing it. It's possible 00:45:46.339 --> 00:45:49.900 that it is doing it because they all share something in common 00:45:49.900 --> 00:45:53.000 that triggers the same immune response that is damaging 00:45:53.000 --> 00:45:56.810 or that they00:02:18,150 --> 00:02:21,330 for 23 years. 00:02:21.330 --> 00:02:24.940 Twenty-three years. She had a wonderful life; 00:02:24.940 --> 00:02:28.780 she has a supporting and loving husband-- 00:02:28.780 --> 00:02:32.319 still he's with her--who works for a high-tech company, 00:02:32.319 --> 00:02:37.470 two super children, enjoy her full-time jobs as a sales manager 00:02:37.470 --> 00:02:42.450 and as a housemaker. Being a housewife or a housemaker, as you know, is 00:02:42.450 --> 00:02:43.950 a full-time job on its own. 00:02:43.950 --> 00:02:48.738 She had two full-time jobs. And she was the source of constant joy 00:02:48.739 --> 00:02:53.120 for her family and friends. She had probably achieved what many will call the 00:02:53.120 --> 00:02:54.900 "American Dream." 00:02:54.900 --> 00:02:57.879 In 1985, that dream came to a stop. 00:02:57.879 --> 00:03:02.140 At the age of 30, and after giving birth to her first child, 00:03:02.140 --> 00:03:06.679 she developed fatigue--fatigue that became worse over the 00:03:06.680 --> 00:03:10.340 next 23 years, becoming disabling 00:03:10.340 --> 00:03:14.100 in 2003. She can only do 30 00:03:14.100 --> 00:03:17.329 percent of what she was capable of doing before she fell ill. 00:03:17.330 --> 00:03:20.730 Even running small errands, like going to grocery 00:03:20.730 --> 00:03:25.230 shopping, has become a major ordeal. Here we have 00:03:25.230 --> 00:03:28.768 a life that has come to a standstill: 00:03:28.769 --> 00:03:33.610 Thirty percent of what she's capable of doing for 23 years. 00:03:33.610 --> 00:03:38.209 So I want you to carefully weigh everything that is being presented to you; this is 00:03:38.209 --> 00:03:39.430 a real case. 00:03:39.430 --> 00:03:43.120 So how is it possible to live with a disease 00:03:43.120 --> 00:03:47.129 that makes you be thirty percent of who you are, and still 00:03:47.129 --> 00:03:50.409 be able to live with that for 23 years? 00:03:50.409 --> 00:03:53.579 In addition to that primary, persistant 00:03:53.580 --> 00:03:56.939 fatigue, she develops other worrisome symptoms: 00:03:56.939 --> 00:04:00.870 Brain fog. It's not uncommon for patients to tell you 00:04:00.870 --> 00:04:06.300 they have brain fog. And it's expressed by significant cognitive impairment-- 00:04:06.300 --> 00:04:11.430 all the way to 30 percent. So 70 percent of her brain function 00:04:11.430 --> 00:04:14.459 was taken, or has been taken, by her illness. 00:04:14.459 --> 00:04:20.250 mental tasks leave her fatigued; compiling information became extremely difficult; 00:04:20.250 --> 00:04:25.330 she feels jumbled and confused. She in addition has had headaches, 00:04:25.330 --> 00:04:28.960 cough, sore throats, unrefreshing sleep. 00:04:28.960 --> 00:04:32.210 She wakes up in the morning as if she would have not slept-- 00:04:32.210 --> 00:04:35.710 she had not slept the night before--with the same level 00:04:35.710 --> 00:04:41.390 of tiredness as when she bed. Post-exertional malaise. 00:04:41.400 --> 00:04:46.540 Not many diseases--and I see respectable physicians here in the audience-- 00:04:46.540 --> 00:04:51.320 not many diseases will give you what the patients with chronic fatigue syndrome 00:04:51.320 --> 00:04:52.330 experience 00:04:52.330 --> 00:04:56.650 when they overdo it. And overdoing it can be just running a small errand. 00:04:56.650 --> 00:05:00.710 Overdoing can be walking a mile. But after that 00:05:00.710 --> 00:05:04.000 level of exercise, or that level 00:05:04.000 --> 00:05:07.889 of, of putting the body through that stress--and it could be mental, 00:05:07.889 --> 00:05:11.440 could be emotional, cognitive 00:05:11.440 --> 00:05:14.680 or physical--they go into a crash 00:05:14.680 --> 00:05:18.380 period. It's not the physical 00:05:18.380 --> 00:05:21.630 sort of strain that you experience when you go and run 00:05:21.630 --> 00:05:25.639 a whole mountain, around miles when you are healthy, your feel tired afterwards 00:05:25.639 --> 00:05:26.370 but you have the 00:05:26.370 --> 00:05:29.690 endorphin kick that makes you feel good because you did a lot of 00:05:29.690 --> 00:05:33.160 exercise or physical activity. It is not that. 00:05:33.160 --> 00:05:37.110 It's a crash where the patient feels sick, many times with the feeling 00:05:37.110 --> 00:05:40.180 of having a flu. In addition to 00:05:40.180 --> 00:05:44.330 post-exertional malaise, she feels muscle pain, 00:05:44.330 --> 00:05:48.440 joint pain. Her primary care provider 00:05:48.440 --> 00:05:52.560 is arguably one of the best internists in the Bay Area. 00:05:52.560 --> 00:05:57.360 And she has been fortunate to have him, because he has been there for her 00:05:57.360 --> 00:06:01.680 for all this period, being sure she doesn't have a cancer, 00:06:01.680 --> 00:06:05.270 low thyroid, a rheumatological disease-- 00:06:05.270 --> 00:06:10.130 he has been so careful in being sure that we don't treat her as (having) chronic fatigue syndrome 00:06:10.130 --> 00:06:13.990 when in fact she could have had something else that can be put in a box, 00:06:13.990 --> 00:06:18.539 and it can be treated from, you know, day one to day X. 00:06:18.539 --> 00:06:22.289 And, most importantly, he believes that her 00:06:22.289 --> 00:06:26.370 illness is real. I cannot tell you that-- 00:06:26.370 --> 00:06:30.900 --whatever we are doing at Stanford that may have worked, and we are 00:06:30.900 --> 00:06:34.720 pleased with those results, may have worked for some patients-- 00:06:34.720 --> 00:06:38.169 it could be still (up) for debate. We still have to do a lot of more work 00:06:38.169 --> 00:06:38.789 to understand 00:06:38.789 --> 00:06:41.900 what are we doing to the patients, that some of them have 00:06:41.900 --> 00:06:46.698 gotten better. But the one thing: a hundred percent of--and not all of the 00:06:46.699 --> 00:06:48.330 patients get better, unfortunately-- 00:06:48.330 --> 00:06:51.340 --but the one thing that I can tell you, that a hundred percent of the patients 00:06:51.340 --> 00:06:52.530 are grateful, 00:06:52.530 --> 00:06:56.490 is when we tell them, "You have a real disease." 00:06:56.500 --> 00:06:59.990 And they break down there. Because for the first time they find somebody in the 00:06:59.990 --> 00:07:01.740 medical community 00:07:01.740 --> 00:07:05.990 telling them, "You are not lying, you are not faking, you are not malingering; 00:07:05.990 --> 00:07:09.940 you have a disease you have no control on." 00:07:09.940 --> 00:07:14.219 And then, then they feel at least validated. So it's very important for-- 00:07:14.220 --> 00:07:18.849 hopefully, one day, my dream is that our medical community 00:07:18.849 --> 00:07:22.830 will produce a formal apology to the patients 00:07:22.830 --> 00:07:26.280 for not having believed them all these years, that they were facing 00:07:26.280 --> 00:07:31.309 a real illness. It's true that currently we don't have a single way 00:07:31.310 --> 00:07:34.610 to determine that somebody has CFS in an objective way. 00:07:34.610 --> 00:07:37.660 It's true that we don't have a single treatment, but 00:07:37.660 --> 00:07:41.840 the patients do have a real disease. 00:07:41.840 --> 00:07:44.948 The fact that the patients give you so much 00:07:44.949 --> 00:07:48.940 history of suffering, and that is incapacitating, 00:07:48.940 --> 00:07:53.160 that when you try to look for objective signs that 00:07:53.160 --> 00:07:58.300 that, that correlates with what they are telling you--that dichotomy between 00:07:58.300 --> 00:08:01.330 they telling you, "I am so sick, I cannot 00:08:01.330 --> 00:08:04.780 even leave the house." But then when you do testing, 00:08:04.780 --> 00:08:08.680 when you examine them, you do not find anything that is 00:08:08.690 --> 00:08:11.810 palpable or tangile, that is not new. 00:08:11.810 --> 00:08:15.759 Even back in the 1900s, when physicians 00:08:15.759 --> 00:08:19.340 who had this special skill 00:08:19.340 --> 00:08:24.200 for having, for finding diseases in the physical exam, like William Osler 00:08:24.200 --> 00:08:28.620 famously said, "In all forms there is a striking lack of accordance 00:08:28.620 --> 00:08:32.140 between the symptoms of which the patients complain and the objective 00:08:32.140 --> 00:08:36.990 changes discoverable by the physician." So it has been more than two hundred years that 00:08:36.990 --> 00:08:42.760 that discordance is known, but what is sad is that it has been equated 00:08:42.760 --> 00:08:46.339 to the patient has something that is in their head, something that they have 00:08:46.339 --> 00:08:50.250 control, just with their minds. So CFS 00:08:50.250 --> 00:08:53.830 is a real disease. It's experienced by 00:08:53.830 --> 00:08:59.620 one to four million Americans, perhaps 17 or more million people (it's worldwide); 00:08:59.620 --> 00:09:04.459 there are no diagnostic tests that can identify with certainty 00:09:04.459 --> 00:09:09.199 the patient. Pneumonia: pneumonia, for example, 00:09:09.200 --> 00:09:12.360 is an infection. And when a patient has cough, 00:09:12.360 --> 00:09:15.899 and fever, and tired, and sore throat, 00:09:15.899 --> 00:09:19.209 we do a chest X-ray and we see something. We see 00:09:19.209 --> 00:09:23.699 a shadow in that chest X-ray, and we say the patient has pneumonia. 00:09:23.700 --> 00:09:27.790 We don't have the equivalent to that shadow in CFS. 00:09:27.790 --> 00:09:31.899 We desperately need that, and this is one of the goals that we have set 00:09:31.899 --> 00:09:35.980 our group at Stanford, is to one day be able to tell our patients, 00:09:35.980 --> 00:09:40.230 "Yes, you have a shadow in your chest X-ray, CFS disease, 00:09:40.230 --> 00:09:43.810 and yes, that validates you. There are no 00:09:43.810 --> 00:09:46.890 definitive treatments, and I'll tell you the 00:09:46.890 --> 00:09:50.890 small progress that we have made at Stanford with some groups of patients in 00:09:50.890 --> 00:09:51.959 this regard, 00:09:51.959 --> 00:09:55.290 and it's true that some patients spontaneously improve, 00:09:55.290 --> 00:10:00.579 but after a certain period of time, their rate of improvement really is small. 00:10:00.580 --> 00:10:04.440 It could be as high as seventy, eighty percent 00:10:04.440 --> 00:10:09.190 in the first year of disease, but it becomes really much lower 00:10:09.190 --> 00:10:12.870 as the years come (pass). 00:10:12.870 --> 00:10:16.950 So what makes CFS such a difficult challenge? 00:10:16.950 --> 00:10:20.990 We have, of course, compassionate colleagues and 00:10:20.990 --> 00:10:24.459 people who are extremely smart in our schools and 00:10:24.459 --> 00:10:27.859 in offices, but what makes it so hard 00:10:27.860 --> 00:10:31.690 not to see it many times as a real disease, for one side, 00:10:31.690 --> 00:10:35.930 is the fact that there are so many symptoms coming from so many angles. 00:10:35.930 --> 00:10:40.290 We physicians have this thinking that if you give us a symptom, 00:10:40.290 --> 00:10:43.310 we try to look for what organ it's coming from. 00:10:43.310 --> 00:10:46.790 So the cough could be coming from the lungs, 00:10:46.790 --> 00:10:51.560 from the heart, from a medication, occasionally from some area of the brain, 00:10:51.560 --> 00:10:55.420 so we start to see where the organ that is involved. 00:10:55.420 --> 00:10:58.550 And many times the symptoms sort of like, 00:10:58.550 --> 00:11:02.670 are [related] to a single system, to an organ, but when the patient 00:11:02.670 --> 00:11:07.180 gives you, with validity, the symptoms coming from so many organs: 00:11:07.180 --> 00:11:10.349 muscle pain, joint pain, brain fog, 00:11:10.350 --> 00:11:14.899 fatigue, et cetera, then it's hard for a physician to take, 00:11:14.899 --> 00:11:18.649 "What do I do with this?" So it's the constellation, 00:11:18.649 --> 00:11:22.430 it's the complexity, it's the fact that they are so hetereogeneous 00:11:22.430 --> 00:11:26.510 that has made this disease difficult to deal with. 00:11:26.510 --> 00:11:29.680 And things will only get worse when we have 00:11:29.680 --> 00:11:33.479 health care systems that only allow physicians for the first visit 00:11:33.480 --> 00:11:37.680 45 minutes or 60 minutes, and for follow-up, 15 minutes or 20 minutes. 00:11:37.680 --> 00:11:38.459 That's going to get 00:11:38.459 --> 00:11:42.250 only worse. The disease is disabling, 00:11:42.250 --> 00:11:46.589 the combination of symptoms--not only is the fatigue the central core 00:11:46.589 --> 00:11:50.519 of the symptom, but what I refer to you as brain fog. 00:11:50.519 --> 00:11:53.950 Unfortunately, the name "chronic fatigue syndrome" 00:11:53.950 --> 00:11:57.589 has not served well the disease or the patients. 00:11:57.589 --> 00:12:01.000 There are other symptoms. It's not just the fatigue. 00:12:01.000 --> 00:12:04.850 And the most and the recognized symptom in patients with chronic fatigue 00:12:04.850 --> 00:12:07.000 syndrome is the cognitive impairment. 00:12:07.000 --> 00:12:11.339 It is real. It is there. It incapacitates patients. 00:12:11.339 --> 00:12:14.380 Patients say that they have difficulty concentrating, 00:12:14.380 --> 00:12:18.230 finding words; they cannot produce the same level 00:12:18.230 --> 00:12:21.230 of executive function that they used to exercise, 00:12:21.230 --> 00:12:24.540 and they cannot sustain those activities for much. 00:12:24.540 --> 00:12:29.120 They also have sleep problems and pains in the joints and muscles. 00:12:29.120 --> 00:12:33.200 They usually have the disease for six months or longer. 00:12:33.200 --> 00:12:37.610 So we are trying to differentiate those situations where you get the fatigue 00:12:37.610 --> 00:12:41.490 and fortunately it goes away 00:12:41.490 --> 00:12:45.860 within a short period of time. So it has generally been agreed upon 00:12:45.860 --> 00:12:49.820 that if you have the fatigue for more than six months is when you have to worry 00:12:49.820 --> 00:12:53.190 about the possibility that initial illness 00:12:53.190 --> 00:12:56.470 could have been the beginning of the nightmare 00:12:56.470 --> 00:13:00.160 that will ensue months or years later. 00:13:00.160 --> 00:13:03.920 Many patients--many patients will tell you 00:13:03.920 --> 00:13:07.240 that their nightmare began with a 00:13:07.240 --> 00:13:10.389 viral-like illness. They will tell you that. They are-- 00:13:10.389 --> 00:13:13.930 you know, the way I see this disease is that, 00:13:13.930 --> 00:13:18.469 it is speaking to us. It is telling us the clue--it's giving us the clues, 00:13:18.470 --> 00:13:21.649 we just have not had the patience 00:13:21.649 --> 00:13:24.980 and the time 00:13:24.980 --> 00:13:28.000 to really listen to the clues that the disease is giving us there. 00:13:28.000 --> 00:13:31.350 But they tell us, "I was totally fine." 00:13:31.350 --> 00:13:35.220 And they give you the month. Sometimes they give you the date, 00:13:35.220 --> 00:13:38.490 the day of the month, and the year, when their whole 00:13:38.490 --> 00:13:42.600 life crumbled, like the patient that I illustrated to you. 00:13:42.600 --> 00:13:47.240 It is important, however, every time that somebody says that they have 00:13:47.240 --> 00:13:47.949 chronic fatigue syndrome, 00:13:47.949 --> 00:13:51.760 that we rule out other potential explanations 00:13:51.760 --> 00:13:55.370 that are more circumscribed to a single 00:13:55.370 --> 00:14:00.880 ideology or cause that can be fixed relatively quick. 00:14:00.880 --> 00:14:04.709 This is this study that validates what the patients have been telling us 00:14:04.709 --> 00:14:08.239 all along. This is a study that was done in Australia, 00:14:08.240 --> 00:14:12.649 where they have the capacity and resources, that as soon as somebody gets 00:14:12.649 --> 00:14:14.500 diagnosed with acute 00:14:14.500 --> 00:14:18.720 infectious mononucleosis, or Epstein-Barr virus infection, 00:14:18.720 --> 00:14:22.250 or another infection that they have common in Australia called 00:14:22.250 --> 00:14:25.290 Q fever. Q fever can go into the lungs, 00:14:25.290 --> 00:14:29.939 can go into the heart. It's called Q fever, caused by an organism called 00:14:29.940 --> 00:14:31.649 Coxiella burnetii. 00:14:31.649 --> 00:14:35.610 Or another infection they call Ross River virus. 00:14:35.610 --> 00:14:39.790 For the purposes of this conversation, these physicians in Australia have the 00:14:39.790 --> 00:14:40.990 capacity 00:14:40.990 --> 00:14:45.149 to register and capture patients who have been dianogised 00:14:45.149 --> 00:14:48.320 with acute infection of any of those three 00:14:48.320 --> 00:14:51.699 kinds: either infectious mononucleosis, 00:14:51.699 --> 00:14:54.939 Q fever, or the Ross River virus. 00:14:54.940 --> 00:14:58.889 And to their surprise, the people who, 00:14:58.889 --> 00:15:02.610 the patients who were followed over time prospectively-- 00:15:02.610 --> 00:15:06.310 and this is the participants that remain 00:15:06.310 --> 00:15:09.899 having fatigue after the acute infection 00:15:09.899 --> 00:15:13.790 was diagnosed here--so in the, in the 00:15:13.790 --> 00:15:16.949 X axis . . . you can follow 00:15:16.949 --> 00:15:21.250 the time after acute infection, six months, twelve months after, 00:15:21.250 --> 00:15:25.149 and here in the . . . Y axis, 00:15:25.149 --> 00:15:29.600 you can see the patients who have fatigue, and you can see obviously patients 00:15:29.600 --> 00:15:30.459 getting better, 00:15:30.459 --> 00:15:34.149 and less having fatigue, but look at the proportion of cases 00:15:34.149 --> 00:15:39.540 that remain fatigued after 12 months. And they follow those patients later; 00:15:39.540 --> 00:15:42.759 Eleven percent of the patients 00:15:42.759 --> 00:15:46.680 develop chronic fatigue syndrome after these acute 00:15:46.680 --> 00:15:50.219 infections. Our patients were telling us that 00:15:50.220 --> 00:15:55.680 all along. And a study had to be done to prove that they were right. 00:15:55.680 --> 00:15:59.420 So it looks like at least in some cases of CFS 00:15:59.420 --> 00:16:03.149 there is an infectious insult at the beginning 00:16:03.149 --> 00:16:06.980 of the illness. Whether it's the infectious agent per se 00:16:06.980 --> 00:16:10.870 or the immune response against that agent, what (affects) it that much 00:16:10.870 --> 00:16:14.829 is unknown at this time. But hopefully one day we'll be able 00:16:14.829 --> 00:16:18.130 to solve that puzzle. 00:16:18.130 --> 00:16:21.509 This is another study done in the United States 00:16:21.509 --> 00:16:25.910 Similar idea. These are other lessons--these are kids. 00:16:25.910 --> 00:16:30.959 They have also been able to capture them at the time they had the acute infection 00:16:30.959 --> 00:16:34.508 and they find that about four percent after 00:16:34.509 --> 00:16:39.240 24 months--four percent--they have had but they have met the criteria 00:16:39.240 --> 00:16:42.769 of chronic fatigue syndrome. So clearly 00:16:42.769 --> 00:16:45.920 there is now proof 00:16:45.920 --> 00:16:50.600 that a patient can go into this mysterious disease, an illness, 00:16:50.600 --> 00:16:53.170 after they have had an acute infection. And 00:16:53.170 --> 00:16:56.509 please note that many of those infections 00:16:56.509 --> 00:17:00.220 also have what we call an asymptomatic phase. In other words, 00:17:00.220 --> 00:17:05.890 people, patients, can get those infections, and not have symptoms. 00:17:05.890 --> 00:17:08.208 What they have found is that in general, 00:17:08.209 --> 00:17:13.750 the more acute, severely ill the patients are, the more severe the disease is 00:17:13.750 --> 00:17:17.348 at the time when they have developed for the first time, 00:17:17.348 --> 00:17:23.539 the higher is the likelihood that they will go into chronic fatigue syndrome. 00:17:23.539 --> 00:17:28.600 So it is really important, and this is just to make one point-- 00:17:28.600 --> 00:17:31.719 is that before we declare someone 00:17:31.720 --> 00:17:36.890 as having chronic fatigue syndrome, not only that six months have passed, 00:17:36.890 --> 00:17:40.620 for now--maybe in the future we will learn to identify 00:17:40.620 --> 00:17:43.789 those who will go into chronic fatigue syndrome very early so we can 00:17:43.789 --> 00:17:45.600 intervene early--but for now, 00:17:45.600 --> 00:17:48.709 the only way we can do it is by waiting. We don't have a way to 00:17:48.710 --> 00:17:49.490 distinguish those 00:17:49.490 --> 00:17:53.340 except that you can say, the more severe cases perhaps, you will have to pay more 00:17:53.340 --> 00:17:54.830 attention to them. 00:17:54.830 --> 00:17:58.899 But it's important that a very good internist, primary care provider, 00:17:58.900 --> 00:18:02.910 family medicine physician, does a comprehensive 00:18:02.910 --> 00:18:06.200 job looking for alternative explanations-- 00:18:06.200 --> 00:18:09.129 psychiatric, psychologic, neurological-- 00:18:09.130 --> 00:18:13.160 Because those can be relatively easily fixed. Be sure that we don't have a 00:18:13.160 --> 00:18:14.929 cancer that has not been diagnosed 00:18:14.929 --> 00:18:18.140 that is causing the fatigue, that is not a low thyroid, 00:18:18.140 --> 00:18:21.830 hormone production. Once that has been done, 00:18:21.830 --> 00:18:25.850 then we look at patients who have had the fatigue for more than six months 00:18:25.850 --> 00:18:30.230 and who have other symptoms. Unfortunately, there is no other way 00:18:30.230 --> 00:18:33.789 to do it. We don't have that shadow in the chest X-ray 00:18:33.789 --> 00:18:36.940 that (lets) you see pneumonia--yet. And 00:18:36.940 --> 00:18:40.260 We couple the fatigue that has lasted for six months 00:18:40.260 --> 00:18:45.270 plus four of any of this impaired concentration of the brain fog, 00:18:45.270 --> 00:18:48.299 sore throat, lymph nodes that are enlarged 00:18:48.299 --> 00:18:51.330 and painful, muscle pain, joint pain, 00:18:51.330 --> 00:18:56.270 new headaches, the unrefreshing sleep, and the post-exertional malaise. 00:18:56.270 --> 00:18:59.490 They are often with symptoms of depression. 00:18:59.490 --> 00:19:03.640 It's not that the depression causes chronic fatigue syndrome. 00:19:03.640 --> 00:19:07.300 It's that they are depressed because their lives have been been ruined, 00:19:07.300 --> 00:19:10.639 their life has been taken away, and they want that life back 00:19:10.640 --> 00:19:14.610 and they cannot have it. So it is unfortunate that 00:19:14.610 --> 00:19:17.879 we tend to see the periphery and not see how 00:19:17.880 --> 00:19:21.650 it evolved. Clinically, 00:19:21.650 --> 00:19:25.900 those patients, their fatigue is not 00:19:25.900 --> 00:19:28.350 alleviated by resting, 00:19:28.350 --> 00:19:32.439 and it's not the result of, because they are doing something 00:19:32.440 --> 00:19:36.630 something and they are not stopping. And in many cases, 00:19:36.630 --> 00:19:39.950 they lose their previous levels of occupational, 00:19:39.950 --> 00:19:43.470 educational, social, or personal activities. 00:19:43.470 --> 00:19:47.320 It's very important to note that many of them 00:19:47.320 --> 00:19:51.129 give you neurological symptoms 00:19:51.130 --> 00:19:54.320 that are hard to put in any category. 00:19:54.320 --> 00:19:58.580 At a meeting we were participating last night 00:19:58.580 --> 00:20:02.260 in, in the Washington area, we were sitting with 00:20:02.260 --> 00:20:06.870 neurologists and other physicians, and it became very clear 00:20:06.870 --> 00:20:10.490 that everybody's seeing the same thing. 00:20:10.490 --> 00:20:13.330 Not only the fatigue, not only the brain fog, 00:20:13.330 --> 00:20:18.100 but these funny tremors, twitches, that we call 00:20:18.100 --> 00:20:22.250 myoclonus fasciculations, things that normally will trigger the possibility of a 00:20:22.250 --> 00:20:23.169 neurlogical disease-- 00:20:23.169 --> 00:20:27.230 these patients are having something in that area. 00:20:27.230 --> 00:20:31.390 so again, it seems like the disease is speaking to us 00:20:31.390 --> 00:20:35.450 in soft tones, and we're just not able to listen to it 00:20:35.450 --> 00:20:39.419 in a careful way. So it is a real disease, 00:20:39.419 --> 00:20:43.100 but it's an infectious, it is immunological, 00:20:43.100 --> 00:20:47.289 it's endocrine, neurological, cardiac, psychiatric, 00:20:47.289 --> 00:20:50.480 and so everybody seems to be looking at it from the wrong angle 00:20:50.480 --> 00:20:53.820 depending on what their area is. And 00:20:53.820 --> 00:20:57.350 hopefully one day will be able to see it three hundred and sixty 00:20:57.350 --> 00:21:01.719 to be able to comprehend better what is really is, what it's doing-- 00:21:01.720 --> 00:21:05.690 the disease to these patients. And part of the problem 00:21:05.690 --> 00:21:10.150 is that, as I said, it's a constellation of systems, so it's a systemic 00:21:10.150 --> 00:21:15.419 challenge; it lasts! It can go on for decades. 00:21:15.419 --> 00:21:20.190 Is it possible that the CFS that one patient has is different than the other? 00:21:20.190 --> 00:21:21.809 Of course it could be possible. 00:21:21.809 --> 00:21:25.639 Like in pneumonia, you have this same shadow in two patients 00:21:25.640 --> 00:21:28.730 but it's caused by a different organism. 00:21:28.730 --> 00:21:32.490 So when you study CFS patients in the air, in general, 00:21:32.490 --> 00:21:36.380 it could be that you are studying different subgroups, and as you try to 00:21:36.380 --> 00:21:37.409 make it a one, 00:21:37.409 --> 00:21:41.159 your findings could be diluted for that reason. 00:21:41.159 --> 00:21:44.390 Also is very likely that the disease evolves. 00:21:44.390 --> 00:21:47.980 It changes. The patient who has illness for less than a year 00:21:47.980 --> 00:21:52.900 possibly will have a different kind of test, positive or negative, 00:21:52.900 --> 00:21:58.408 than someone who has had the disease for ten or twenty years. 00:21:58.409 --> 00:22:01.789 I have to bring up this study. Because in 00:22:01.789 --> 00:22:05.640 our infectious diseases community--so I told you that many patients tell you 00:22:05.640 --> 00:22:07.210 that there is an 00:22:07.210 --> 00:22:11.270 infection at the beginning of the illness--this is this study that has been 00:22:11.270 --> 00:22:16.940 cited as a study that shows that an anti-microbial intervention 00:22:16.940 --> 00:22:20.570 does not work for patients with chronic fatigue syndrome. It was a study that was 00:22:20.570 --> 00:22:22.129 published in the late 80s, 00:22:22.130 --> 00:22:27.940 where they took 27 patients. They had high titers against Epstein-Barr virus 00:22:27.940 --> 00:22:31.230 virus; they had been ill for at least seven years; 00:22:31.230 --> 00:22:34.610 and they gave those patients acyclovir for thirty 00:22:34.610 --> 00:22:37.908 days. So they got IV for seven days, 00:22:37.909 --> 00:22:41.250 and oral for thirty days. So no more 00:45:56.810 --> 00:46:00.730 similar mechanisms of damaging, or immunopathology, 00:46:00.730 --> 00:46:07.140 as also is known. The fact that the disease can be pressing for so many years 00:46:07.140 --> 00:46:10.598 is telling us something. It's whispering to us something. 00:46:10.599 --> 00:46:14.810 The fact that somebody could have a disease and not die of it 00:46:14.810 --> 00:46:19.109 for so long is giving us clues of the mechanism. 00:46:19.109 --> 00:46:22.339 If it's an infection that is doing it, it will mean 00:46:22.339 --> 00:46:26.390 that the infectious agent is capable of coming out of the hiding place 00:46:26.390 --> 00:46:31.400 at a low level. And the immune system attacks the infection, 00:46:31.400 --> 00:46:34.290 successfully puts that pathogen back in the hiding place, 00:46:34.290 --> 00:46:37.859 but it's the same immune response perhaps that is making the patients sick. 00:46:37.859 --> 00:46:41.670 Ad it just perpetuates the cycle. The patients tell us, 00:46:41.670 --> 00:46:45.450 they had been telling us for years, 00:46:45.450 --> 00:46:49.399 "I get this fluctuating level(s) of disease." 00:46:49.400 --> 00:46:53.240 And I think the immune system is acting as a double-edged sword; 00:46:53.240 --> 00:46:57.290 it's putting that organism back in (its) hiding place, but it's making the patient 00:46:57.300 --> 00:46:59.420 possibly sick. 00:46:59.420 --> 00:47:04.290 So the other observation is that most of the patients are women; 00:47:04.290 --> 00:47:07.349 most of them get better during pregnancy 00:47:07.349 --> 00:47:10.640 and most of them get worse after birth. 00:47:10.640 --> 00:47:13.670 Remember that patient that I mentioned to you: that she got the disease 00:47:13.670 --> 00:47:17.170 after the birth of her son. So that suggests 00:47:17.170 --> 00:47:21.540 an autoimmune disease, or an HLA association. Many diseases 00:47:21.540 --> 00:47:24.670 that have been found to be autoimmune had that exact 00:47:24.670 --> 00:47:27.950 same behavior. Lastly, 00:47:27.950 --> 00:47:32.290 I wanna comment to you, comment with you, 00:47:32.300 --> 00:47:35.869 the highly publicized study 00:47:35.869 --> 00:47:39.790 that came out of London where they 00:47:39.790 --> 00:47:42.920 did what is called adaptive pacing therapy, 00:47:42.920 --> 00:47:47.440 cognitive behavior therapy, or graded exercise therapy, 00:47:47.440 --> 00:47:50.960 or simply, a specialized medical care 00:47:50.960 --> 00:47:55.590 for patients with chronic fatigue syndrome. Adaptive pacing therapy 00:47:55.590 --> 00:47:58.550 is to tell the patient, "Do what you feel, but do not 00:47:58.550 --> 00:48:01.780 overdo it. Cognitive behavioral therapy 00:48:01.780 --> 00:48:05.270 is they work with a counselor, with a psychologist, 00:48:05.270 --> 00:48:10.470 to be sure that they overcome the fear of doing things, because they would crash, 00:48:10.470 --> 00:48:13.759 but they also get the same message: avoid the crashes. 00:48:13.760 --> 00:48:16.930 But this time they do it under cognitive 00:48:16.930 --> 00:48:21.400 behavioral intervention. Graded exercise therapy 00:48:21.400 --> 00:48:24.690 is they work with physical therapy individuals 00:48:24.690 --> 00:48:28.880 with the same goal--not to crash--but they do have some kind of 00:48:28.880 --> 00:48:32.440 schedule, graded exercise activity. 00:48:32.440 --> 00:48:36.100 in all the groups, either adaptive pacing therapy, 00:48:36.100 --> 00:48:40.200 cognitive behavior, graded exercise therapy, the main goal was to 00:48:40.200 --> 00:48:43.640 avoid the patient crashing, however the idea 00:48:43.640 --> 00:48:47.348 was to achieve that through these different means that I described to you. 00:48:47.349 --> 00:48:51.490 And a fourth group, a specialist medicare care-- 00:48:51.490 --> 00:48:55.459 those patients simply got a good physician who new chronic fatigue syndrome 00:48:55.460 --> 00:48:58.500 but did nothing other than just provide general medical care. 00:48:58.500 --> 00:49:01.710 And this is what was found. 00:49:01.710 --> 00:49:05.809 So. The patients who got the adaptive pacing therapy 00:49:05.809 --> 00:49:09.880 just don't don't crash, trust your instincts-- 00:49:09.880 --> 00:49:13.339 basically did not, so, in this score-- 00:49:13.339 --> 00:49:16.869 in this score, going down is getting better. 00:49:16.869 --> 00:49:20.380 and really, these patients are really 00:49:20.380 --> 00:49:23.450 Sick. And in this case... 00:49:23.450 --> 00:49:27.790 In this case, it was clearly that the patients did not improve 00:49:27.790 --> 00:49:31.509 by simply telling them, "Trust your instincts." 00:49:31.510 --> 00:49:34.700 The patients who had the cognitive behavioral therapy, 00:49:34.700 --> 00:49:38.430 they actually improved their performance 00:49:38.430 --> 00:49:41.500 but they did not get cured from CFS. 00:49:41.500 --> 00:49:45.250 It is so sad that this study is being cited 00:49:45.250 --> 00:49:48.390 as "cognitive behavorial therapy is curing CFS." 00:49:48.390 --> 00:49:53.660 It's not true. The patients simply got better, and it's good that the patients got better, 00:49:53.660 --> 00:49:57.828 it was statistically significant, but they were far from going back to 00:49:57.829 --> 00:49:59.260 their normal levels. 00:49:59.260 --> 00:50:03.500 The same thing with the graded exercise therapy--they got better 00:50:03.500 --> 00:50:07.650 in a statistically significant manner, but they were far from being completely well. 00:50:07.650 --> 00:50:11.540 And the same thing, the same findings were for the physical 00:50:11.540 --> 00:50:15.940 function in that regard. So that the 00:50:15.940 --> 00:50:19.700 same authors of the papers said, "Our finding that 00:50:19.700 --> 00:50:23.890 (the) study treatments, like those, were only moderately 00:50:23.890 --> 00:50:26.529 effective," they are not saying that they are curing CFS, 00:50:26.530 --> 00:50:32.430 also suggests that researching to more effective treatments are needed 00:50:32.430 --> 00:50:37.569 and that the fact that behavioral intervention means that patients get better 00:50:37.569 --> 00:50:40.680 by no means means that this is psychological in nature. 00:50:40.680 --> 00:50:45.900 And I have to say that, because I had a very sad conversation with a family 00:50:45.100 --> 00:50:46.530 member of a patient who 00:50:46.530 --> 00:50:49.720 was doubting that our patient had the disease, 00:50:49.720 --> 00:50:53.200 and cited this study to say that now 00:50:53.200 --> 00:50:56.160 there was proof that "CFS was psychological" 00:50:56.160 --> 00:51:00.240 and that with psychological intervention, the patients "could get cured." This is far 00:51:00.240 --> 00:51:01.109 from truth, 00:51:01.109 --> 00:51:04.839 from the actual findings of the study. So I think we have 00:51:04.839 --> 00:51:08.819 lots of work to do; we need 00:51:08.819 --> 00:51:13.160 all the best minds at Stanford, and we are gathering the best minds at Stanford 00:51:13.160 --> 00:51:16.920 around the team. We need to find an objective, 00:51:16.920 --> 00:51:20.430 a form of saying, "yes,the patient has CFS"; 00:51:20.430 --> 00:51:23.558 we need to find black levels-- 00:51:23.559 --> 00:51:27.740 biomarkers that can identify the situation; we need to find ways to 00:51:27.740 --> 00:51:31.580 identify the subgroup, which is the pathogen behind-- 00:51:31.590 --> 00:51:35.579 it's possible that there are patient with CFS that are not infectious as well. 00:51:35.579 --> 00:51:39.520 We need to find those agents and to the right trials. 00:51:39.520 --> 00:51:43.109 The attitude that was have taken at Stanford 00:51:43.109 --> 00:51:47.529 reminds me of what we want to do, is similar to what's found in this 00:51:47.530 --> 00:51:50.790 late 70s movie (The Wild Child) from Francois Truffaut: 00:51:50.790 --> 00:51:54.450 they have found this child in the forest of France. 00:51:54.450 --> 00:51:59.439 it was wild. Did not know how to speak, perhaps couldn't even hear. 00:51:59.440 --> 00:52:03.869 Basically it was a wild child with an entity of behavior 00:52:03.869 --> 00:52:07.329 that was not understood at all. However, 00:52:07.329 --> 00:52:11.690 when he was brought to a room where a physician who wanted to really 00:52:11.690 --> 00:52:14.890 help him and understand him, was trying to describe 00:52:14.890 --> 00:52:19.890 the length of his hair, teeth, numbers of scars in his skin, 00:52:19.890 --> 00:52:22.160 et cetera; made, uh, 00:52:22.160 --> 00:52:25.308 (an) observation. The kid 00:52:25.309 --> 00:52:28.420 did not react when a heavy noise 00:52:28.420 --> 00:52:31.730 was produced in the room. And he said, "Did you notice?" 00:52:31.730 --> 00:52:36.590 He didn't react to that loud noise. He's deaf. 00:52:36.590 --> 00:52:40.300 Then, another man who has seen the kid in the wild, 00:52:40.300 --> 00:52:44.200 from the village, says, "How can he be deaf 00:52:44.200 --> 00:52:47.430 when in the large I've seen him turn around 00:52:47.430 --> 00:52:50.770 when a nut was cracked behind him?" 00:52:50.770 --> 00:52:55.400 So the physician who is trying to make the observation says, "Write this: 00:52:55.400 --> 00:52:58.900 Indifferent to loud noises... whereas he turns around 00:52:58.900 --> 00:53:02.170 when a nut is cracked behind him." So 00:53:02.170 --> 00:53:06.339 it's really having a candid attitude towards this disease: 00:53:06.339 --> 00:53:10.200 observing what is there, what the disease is telling us, what I think that one day, 00:53:10.200 --> 00:53:14.790 hopefully, we'll be able to (use to) make a difference. And that would not be possible with a team. 00:53:14.790 --> 00:53:18.819 So we're very grateful to the Brennan and Taskey families for their support; 00:53:18.819 --> 00:53:23.359 Lindsey Merrihew, who is right here in the room--none of these things 00:53:23.359 --> 00:53:27.140 trust me, would have been possible without Lindsey. She's really the head 00:53:27.140 --> 00:53:31.290 and the mover and the doer in the team. And all the people 00:53:31.300 --> 00:53:35.460 below her: Jane Norris, Amber Ruiz, Dr. Marzie Zinn, who is also here, 00:53:35.460 --> 00:53:38.540 Dr. Marcie Zinn has given the challenge of 00:53:38.540 --> 00:53:42.500 helping us to understand the brain fog and how to measure. 00:53:42.500 --> 00:53:45.780 So none of those things would have happened without the intervention 00:53:45.780 --> 00:53:51.910 of this great team. Thank you. 00:53:51.910 --> 00:53:55.420 [Question asked] Now the doctor has asked the question that, 00:53:55.420 --> 00:53:58.470 you know, obviously, this, 00:53:58.470 --> 00:54:01.490 uh, we have a problem. 00:54:01.490 --> 00:54:04.609 And it's the waiting time. Lindsey, what is 00:54:04.609 --> 00:54:08.430 the waiting time now? 00:54:08.430 --> 00:54:13.440 Two to three years. So we are trying to desperately try to, 00:54:13.440 --> 00:54:16.609 um, to to cope with the high demand. 00:54:16.609 --> 00:54:20.440 There is a physician in the area, in El Camino Hospital, 00:54:20.440 --> 00:54:23.980 [Dr. Andreas Kogelnik]. So [K- 00:54:23.980 --> 00:54:27.690 0-G-E-L-N-I-K.] 00:54:27.690 --> 00:54:30.240 And Lindsey and I can give you his contact information, 00:54:30.240 --> 00:54:33.970 who is seeing now patients with chronic fatigue syndrome, with an approach 00:54:33.970 --> 00:54:37.649 similar to ours. So that has helped us, to 00:54:37.650 --> 00:54:40.900 have patients being seen by him. 00:54:40.900 --> 00:54:44.599 Thank you, yeah, you are correct, it's right here, his name: 00:54:44.599 --> 00:54:48.230 Kogelnik, actually. K-O-G. Kogelnik. 00:54:48.230 --> 00:54:52.190 Um, so, but... you know, our hope, 00:54:52.190 --> 00:54:55.790 our goal, in addition to one day 00:54:55.790 --> 00:54:59.220 be able to understand the disease and erradicate it, 00:54:59.220 --> 00:55:02.868 in addition to that dream, is that we need to desperately bring 00:55:02.869 --> 00:55:06.319 education our colleagues, medical students, 00:55:06.319 --> 00:55:09.720 fellows residents, so they can perpetuate that 00:55:09.720 --> 00:55:12.730 model. [Question asked] So the question was made that, 00:55:12.730 --> 00:55:17.309 what was the dose that was used in the study that we cited in the late 80s, 00:55:17.309 --> 00:55:20.849 where patients with chronic fatigue syndrome were treated with acyclovir, 00:55:20.849 --> 00:55:23.859 and the answer is that they used the standard dose 00:55:23.859 --> 00:55:26.930 for that time, that were not high doses. 00:55:26.930 --> 00:55:30.710 And what is striking is they used only five weeks, 00:55:30.710 --> 00:55:34.400 yet they went out and made that as the Bible, 00:55:34.400 --> 00:55:38.329 that antiviral intervention does not work for CFS. 00:55:38.329 --> 00:55:41.670 [Question asked] The question is, if valgancyclovir is available. 00:55:41.670 --> 00:55:46.150 Yes. It is available; it's approved by the FDA; 00:55:46.150 --> 00:55:49.470 when we did the trial, we went to the FDA, 00:55:49.470 --> 00:55:53.589 got the permission at the FDA to use it for this other indication. 00:55:53.589 --> 00:55:56.630 It needs medical supervision-- 00:55:56.630 --> 00:55:59.950 there is a safety issue with the blood cells, but 00:55:59.950 --> 00:56:03.529 if you have proper supervision, that usually is not an issue. 00:56:03.530 --> 00:56:06.990 There is a question mark on the long-term use about, 00:56:06.990 --> 00:56:11.529 in animals, it can cause cancer, we do not know if that happens in humans, but it 00:56:11.530 --> 00:56:12.900 has to always be 00:56:12.900 --> 00:56:16.890 discussed with your provider in that regard. 00:56:16.890 --> 00:56:19.339 [Question asked] So the question is, like--could people, knowing 00:56:19.339 --> 00:56:24.569 that some of these infections can do that devastation, can you do something 00:56:24.569 --> 00:56:28.359 in a prophylactic manner, to prevent that [you're] going to that 00:56:28.359 --> 00:56:32.390 unhealthy cascade. Not that we know of. 00:56:32.390 --> 00:56:37.848 If we were to write something in a magazine, in a journal, we 00:56:37.849 --> 00:56:41.619 would have to say "nothing is known." If we were having a 00:56:41.619 --> 00:56:45.910 coffee table conversation, then you could say some things like, 00:56:45.910 --> 00:56:50.149 "Please don't--you know, there are many patients who, when they are sick, they try 00:56:50.150 --> 00:56:53.900 to go to the extreme, they try to to back to work naturally. 00:56:53.900 --> 00:56:57.740 I would suggest that common-sense measures of rest when they have the 00:56:57.740 --> 00:56:58.759 acute illness 00:56:58.760 --> 00:57:03.859 be exaggerated, in fact--that they take more time to rest. 00:57:03.859 --> 00:57:07.790 The other thing that we have found, but this is totally anecdotal, is some of the 00:57:07.790 --> 00:57:11.710 kids of our colleagues at Stanford who have come down with the acute 00:57:11.710 --> 00:57:15.160 infections, and we have measured the [levels] and they had been positive; 00:57:15.160 --> 00:57:18.299 we had given the antibiotic right there 00:57:18.299 --> 00:57:21.780 and it seems like--but it's very anecdotal--that they 00:57:21.780 --> 00:57:25.329 recover. But, anecdotal. [Question asked] The question is about 00:57:25.329 --> 00:57:28.980 the levels of HSV-1, or HSV-2, 00:57:28.980 --> 00:57:33.730 and even with HSV-6--do they travel travel together? 00:57:33.730 --> 00:57:37.780 Preliminarily, it seems like the EBV and HSV-6, 00:57:37.780 --> 00:57:42.569 they travel together in a surgroup of patients. We thought that that surgroup was gonna be 00:57:42.569 --> 00:57:46.420 large, the one that we allegedly found, 00:57:46.420 --> 00:57:49.549 but he seems like it's a small surgroup. 00:57:49.549 --> 00:57:54.220 It's rare to have a patient with HSV-1 and HSV-6. 00:57:54.220 --> 00:57:58.240 We don't know why yet. Or HSV-2 and HSV-6. 00:57:58.240 --> 00:58:01.490 It's not not uncommon to have HSV-1 and HSV-2. 00:58:01.490 --> 00:58:05.118 And the levels of antibodies seems to be high. 00:58:05.119 --> 00:58:09.150 We have had a surgroup of patients with 00:58:09.150 --> 00:58:12.260 HSV-2, genital, HSV-1, 00:58:12.260 --> 00:58:16.890 oral blisters, and we have intervened them with acyclovir, which is a much 00:58:16.890 --> 00:58:19.180 simpler drug to give. 00:58:19.180 --> 00:58:22.419 And after a year, year-and-a-half intervention, 00:58:22.420 --> 00:58:26.240 It seems that we see these recoveries that are truly dramatic. 00:58:26.240 --> 00:58:30.618 In a surgroup of patients. Ideally we should do 00:58:30.619 --> 00:58:34.720 a randomized trial; I'm trying to see how we can come up with the funds 00:58:34.720 --> 00:58:38.640 to do the right study, similar to the other, to prove that that's the case. 00:58:38.640 --> 00:58:43.500 [Questions asked] Two questions: one is, if the drugs that I show you, the one that we have used, 00:58:43.500 --> 00:58:48.200 if they're anti-retroviral, meaning anti-HIV drugs, 00:58:48.200 --> 00:58:52.140 what I have shown you--emphasize that--what I have shown you 00:58:52.140 --> 00:58:55.540 they are not anti-retrovirals; they are not anti-HIV. 00:58:55.540 --> 00:58:58.710 And the second question: if there, 00:58:58.710 --> 00:59:01.920 if there is like a stem cell base for the disease, 00:59:01.920 --> 00:59:06.339 because the virus can get into, some other viruses can get into the genetic 00:59:06.339 --> 00:59:09.710 code, and the answer is, "not as far as we know." 00:59:09.710 --> 00:59:13.420 It seems like it has to do more with the germ line cells. 00:59:13.420 --> 00:59:16.460 The very early cells, but not stem cell 00:59:16.460 --> 00:59:21.530 based. And as far as we know it's not stem-cell based. 00:59:21.530 --> 00:59:24.960 But there is very litle known about that part. 00:59:24.960 --> 00:59:29.140 [Question asked] So the question is about: if long-term, 00:59:29.140 --> 00:59:33.290 careful, safe, thoughtful, 00:59:33.300 --> 00:59:37.619 antiviral or anti-microbial intervention can result in the improvement of 00:59:37.619 --> 00:59:43.890 chronic diseases like this. So that's the model that we are operating. So the-- 00:59:43.890 --> 00:59:46.890 if you see what we're doing behind, it suggests that 00:59:46.890 --> 00:59:50.240 infection at low levels can do a lot of stuff. That's 00:59:50.240 --> 00:59:53.259 the model that we are using. And then that's-- 00:59:53.260 --> 00:59:56.410 So pressing that for long periods of time should improve. So 00:59:56.410 --> 01:00:00.980 the question suggests the possibility that what about if we did that, 01:00:00.990 --> 01:00:05.640 for the long term effects of varicella-zoster virus, or shingles virus 01:00:05.640 --> 01:00:09.879 in terms of pain, this is well known, that it can do this problem. 01:00:09.880 --> 01:00:13.670 Preliminary--but again, just two small patients, but 01:00:13.670 --> 01:00:18.520 highly gratifying. We have patients who had come to us for five years of 01:00:18.520 --> 01:00:21.720 pain, that is clearly what we call the 01:00:21.720 --> 01:00:24.910 "herpes without rash." 01:00:24.910 --> 01:00:28.470 and this woman, after like a year and a half of acyclovir, is 01:00:28.470 --> 01:00:29.430 back to like, 01:00:29.430 --> 01:00:32.930 smile, bubbly personality, normal-- 01:00:32.930 --> 01:00:36.690 those are anecdotal. The point is, 01:00:36.690 --> 01:00:41.790 I think it calls for that. It calls for patients who have the shingles 01:00:41.790 --> 01:00:44.490 to be randomized to long term antiviral suppression 01:00:44.490 --> 01:00:49.598 versus not to show whether it has an impact on the post-herpetic pain 01:00:49.599 --> 01:00:52.690 or neuralgia. Very good point. [Question asked] What about 01:00:52.690 --> 01:00:57.300 families who share the same environment, who could have the same markers. And, 01:00:57.300 --> 01:01:01.599 the right study has not been done, though we do have, 01:01:01.599 --> 01:01:06.910 I think it's--correct me if I'm wrong, Lindsey, but we have four families now, 01:01:06.910 --> 01:01:11.490 four families, in whom they share the markers, 01:01:11.490 --> 01:01:14.400 and not all of them express the disease. So it looks like 01:01:14.400 --> 01:01:18.910 something else is needed. So we have four families who had that behavior. 01:01:18.910 --> 01:01:23.200 So it seems that you need more than the infection to express disease. 01:01:23.200 --> 01:01:26.500 [Question asked] The question is, are we testing patients for XMRV. 01:01:26.500 --> 01:01:30.990 So we asked the Microbiology Department at Stanford 01:01:30.990 --> 01:01:33.579 and they are stepping up to the plate. They are 01:01:33.579 --> 01:01:38.109 setting up the test. We need to find a few more resources, but they are, 01:01:38.109 --> 01:01:41.420 they are doing it. And some of our patients are doing it 01:01:41.420 --> 01:01:44.780 through the other--it is a commercial laboratory that now, 01:01:44.780 --> 01:01:48.170 that's it. Good question. [Question asked] The question is are there any 01:01:48.170 --> 01:01:52.430 clinical trials? There are clinical trials of (a) different nature and kind. 01:01:52.430 --> 01:01:55.848 There is, for example, a clinical trial with interferon. 01:01:55.849 --> 01:01:59.650 Interferon is an antiviral, and it's given to patients with the hope that they 01:01:59.650 --> 01:02:03.839 will recover. And that's (they are) the Nevada group. 01:02:03.839 --> 01:02:07.490 There are others in Europe that obviously our patients will not have access to. 01:02:07.490 --> 01:02:11.430 Our idea, our dream, is to have 01:02:11.430 --> 01:02:14.879 a whole group at Stanford that would just do 01:02:14.880 --> 01:02:18.440 clinical trials for these kinds of patients. But that is an 01:02:18.440 --> 01:02:22.839 infrastructure that is relatively large. And unfortunatel, the NIH 01:02:22.839 --> 01:02:26.420 does not give much money for clinical trials, and that's 01:02:26.420 --> 01:02:30.900 unfortunate. [Question asked] So the question is about the role of alternative treatments. 01:02:30.900 --> 01:02:35.180 What (I've) shown you, the role of cognitive-behavioral intervention, 01:02:35.180 --> 01:02:39.520 the, sort of like, physical therapy intervention, 01:02:39.520 --> 01:02:42.799 clearly points to the fact that there are 01:02:42.799 --> 01:02:46.920 things that patients can do that could be thoughtful, 01:02:46.920 --> 01:02:50.619 not expensive, that could work for the patient. 01:02:50.619 --> 01:02:53.900 So there are things that the patients can do, and they can 01:02:53.900 --> 01:02:57.240 be helped. The answer is yes. And they are in the alternative 01:02:57.240 --> 01:03:02.288 [Question asked] The relationship--is there any any relationship between fatigue, 01:03:02.289 --> 01:03:05.559 that is temporal, versus chronic fatigue, 01:03:05.559 --> 01:03:08.579 because as it's pointed (out), some interventions 01:03:08.579 --> 01:03:11.630 from a good cup of coffee, or provigil, 01:03:11.630 --> 01:03:14.960 or ritaline, make patients with short-term fatigue 01:03:14.960 --> 01:03:18.950 better. There is a subset of patients with chronic fatigue 01:03:18.950 --> 01:03:22.299 syndrome that experience that temporal improvement with those same 01:03:22.299 --> 01:03:23.369 interventions, 01:03:23.369 --> 01:03:27.390 but they are not lasting. All of them tell us, 01:03:27.390 --> 01:03:30.680 when they use those interventions, they basically lead them to 01:03:30.680 --> 01:03:33.788 overdo it and crash. And it's very 01:03:33.789 --> 01:03:38.000 short-term--the effect is very short-term. 01:03:38.000 --> 01:03:42.300 We don't know if the same thing that causes fatigue 01:03:42.300 --> 01:03:46.100 are the same mechanisms that cause chronic fatigue. Our suspicion is that there are 01:03:46.100 --> 01:03:50.510 two different things doing it. Because the patient who had the chronic fatigue, 01:03:50.510 --> 01:03:53.530 more than the fatigue, they have all these other other symptoms. 01:03:53.530 --> 01:03:56.910 Many of them describe--it's like having a bad flu 01:03:56.910 --> 01:04:00.618 going on for years, or for decades. [Question asked] So the question is, are we 01:04:00.619 --> 01:04:04.200 seeing family members of patients with chronic fatigue syndrome 01:04:04.200 --> 01:04:07.859 higher incidents of autoimmune problems? 01:04:07.859 --> 01:04:10.980 The answer is yes. It seems like they tell us stories 01:04:10.980 --> 01:04:14.900 about patients having a higher--the patients tend to have more 01:04:14.900 --> 01:04:18.410 thyroid problem(s) of the autoimmune type. Um, 01:04:18.410 --> 01:04:22.288 we are starting to pay attention to vitiligo, which is 01:04:22.289 --> 01:04:26.200 whitening of the skin when the melanocytes are attacked by 01:04:26.200 --> 01:04:29.680 antibodies. So it seems like there is another 01:04:29.680 --> 01:04:33.348 clue towardas autoimmunity there. 01:04:33.349 --> 01:04:36.480 [Question asked] Are the HSV-6 titers easily done and the answer is 01:04:36.480 --> 01:04:40.380 yes. We don't have any commercial tie with 01:04:40.380 --> 01:04:44.000 anybody. But there is a lot that we suggest 01:04:44.000 --> 01:04:47.130 where the HSV-6 titers can be done, and its 01:04:47.130 --> 01:04:50.609 focus, only because we are familiar with their numbers, 01:04:50.609 --> 01:04:55.470 we have learned to to know what is low, what is medium, what is high. 01:04:55.470 --> 01:04:59.240 But we have no commercial connection with them, but focus laboratory 01:04:59.240 --> 01:05:02.720 appears to be reliable in giving us titers that we can 01:05:02.720 --> 01:05:07.189 sort of like, act upon. [Question] So it's been said that there are, 01:05:07.190 --> 01:05:11.299 there is a support group based in Mountain View, 01:05:11.299 --> 01:05:14.390 that there is a sign up sheet outside here, 01:05:14.390 --> 01:05:17.450 and it's important to share 01:05:17.450 --> 01:05:20.618 these experiences. It's important to 01:05:20.619 --> 01:05:25.180 bring this together, and as it was shown in that study in The Lancet, 01:05:25.180 --> 01:05:29.379 it sounds like having interventional, behavioral intervention, 01:05:29.380 --> 01:05:31.160 cognitive intervention, 01:05:31.160 --> 01:05:34.279 it seems like it helps. And it's very important that, 01:05:34.280 --> 01:05:38.859 that--do not let people talking to--that study proves 01:05:38.859 --> 01:05:42.130 that CFS can be cured, or that that study proves 01:05:42.130 --> 01:05:45.849 that it's psychological. In addition to what you said, they excluded patients 01:05:45.849 --> 01:05:50.289 who couldn't come to the hospital, so the sickest patients didn't make it into the trial. 01:05:50.289 --> 01:05:53.930 Though their scores were really low in terms of performance, 01:05:53.930 --> 01:05:57.609 so in addition to the selection issues, 01:05:57.609 --> 01:06:01.470 the study does not prove a psychological (connection) and does not prove 01:06:01.470 --> 01:06:04.629 that that's the way to cure patients. [Question asked] Is there any 01:06:04.630 --> 01:06:08.240 there any neurological or phenotyping difference, phenotype difference, between 01:06:08.240 --> 01:06:10.709 those patients who come down with an 01:06:10.710 --> 01:06:14.380 illness, with CFS, after they have an acute illness, 01:06:14.380 --> 01:06:18.369 particularly an infectious illness, versus those who have their onset 01:06:18.369 --> 01:06:22.619 not associated with an infection? Not that we know of, 01:06:22.619 --> 01:06:26.390 but we are separating them by when we take the history, 01:06:26.390 --> 01:06:29.670 and in the analysis that we are doing, looking for pathogens, or for immune 01:06:29.670 --> 01:06:31.230 response abnormalities-- 01:06:31.230 --> 01:06:34.920 we are taking that into account. So hopefully we'll be able 01:06:34.920 --> 01:06:39.880 to answer--no, I think he's asking like, independent of (whether) it's a woman or man, 01:06:39.880 --> 01:06:43.750 is there a difference between those who started the illness with an infection, 01:06:43.750 --> 01:06:47.700 versus those do do not start the disease with an infection. 01:06:47.700 --> 01:06:51.180 It is well-known that 75 percent of the patients with 01:06:51.180 --> 01:06:55.780 CFS, 75 percent are women. Now 01:06:55.790 --> 01:06:59.520 if we were to take women alone, there are women who started their CFS 01:06:59.520 --> 01:07:04.849 without an infection. And so the sample size on the second study was very small. 01:07:04.849 --> 01:07:08.119 But women can start their CFS with not an infectious illness. 01:07:08.119 --> 01:07:11.460 And the question is, are there differences between those who, 01:07:11.460 --> 01:07:14.670 who tell you the precise time where they started, 01:07:14.670 --> 01:07:18.900 versus those who who did not. So the question is, when the patients get a 01:07:18.900 --> 01:07:20.100 viral illness, 01:07:20.100 --> 01:07:23.339 some of them go into CFS and some do not. 01:07:23.339 --> 01:07:28.200 The most common factor that has been associated in the study 01:07:28.200 --> 01:07:31.400 (that) have looked at this, is severity of the illness. 01:07:31.400 --> 01:07:34.799 So the more severe the illness, the more likely they are 01:07:34.799 --> 01:07:37.940 to go into having the illness-- 01:07:37.940 --> 01:07:42.130 as far as it's known. [Question asked] Well thanks to the support of one of our 01:07:42.130 --> 01:07:45.480 patients, we started, Lindsey actually, 01:07:45.480 --> 01:07:48.920 and Mrs. Kaski are really the people who 01:07:48.920 --> 01:07:52.490 we have to thank. We started a website 01:07:52.490 --> 01:07:56.599 where, at Stanford, and, Lindsey, the name of the website please? 01:07:56.599 --> 01:07:59.720 so http://chronicfatigue.stanford.edu/ 01:07:59.720 --> 01:08:03.578 ...and there we are starting to put up as many resources as 01:08:03.579 --> 01:08:06.950 we can, everything that we have learned about, 01:08:06.950 --> 01:08:10.868 of the disease for the past few years. [Question asked] We know that some patients 01:08:10.869 --> 01:08:14.630 crash. Have we measured the amount of dividers 01:08:14.630 --> 01:08:17.899 or cytokines during those crash periods? 01:08:17.899 --> 01:08:22.540 so we attempted to do that in the study that I showed you, where we found differences. 01:08:22.540 --> 01:08:26.350 But the numbers are so small, and we didn't see any differences. 01:08:26.350 --> 01:08:29.969 But I think it's a matter of just doing that. 01:08:29.969 --> 01:08:34.799 The tough part of studying that is, how can you justify 01:08:34.799 --> 01:08:39.890 to ask a patient, "Take this drug. It's gonna make you sick, 01:08:39.890 --> 01:08:42.620 and we'll study you." So ethically it's hard. [Question asked] 01:08:42.620 --> 01:08:46.799 These viruses are latent. They are there for the life of the patient. 01:08:46.799 --> 01:08:50.299 So we are not suggesting that with these long-term anti- 01:08:50.299 --> 01:08:53.509 viral interventions we are eradicating the 01:08:53.509 --> 01:08:57.549 virus out of the body, we are trying to, if our theory is correct, 01:08:57.549 --> 01:09:01.819 bring them under control. So--and you are absolutely correct-- 01:09:01.819 --> 01:09:04.969 I think that part of the reason it has eluded 01:09:04.969 --> 01:09:09.799 our understanding of the disease, is that they are at very low levels 01:09:09.799 --> 01:09:12.939 even when they are causing disease. That is correct. 01:09:12.939 --> 01:09:16.108 [Question asked] It's more common in women--have we seen mothers 01:09:16.109 --> 01:09:20.120 giving it to their daughters? So we have, 01:09:20.120 --> 01:09:24.599 sadly, a few cases where that has been the case. 01:09:24.600 --> 01:09:28.238 And mostly related to that situation, where dividers 01:09:28.238 --> 01:09:32.448 integrate into the chromosome, the human herpes--so herpes viruses 01:09:32.448 --> 01:09:35.689 normally do not integrate into the chromosome 01:09:35.689 --> 01:09:39.669 like HIV does, like the XMRV does, 01:09:39.670 --> 01:09:44.120 herpes viruses are known for not doing that. But the HSV-6 has found a 01:09:44.120 --> 01:09:48.839 clever way to do it, and they--those patients 01:09:48.839 --> 01:09:53.420 seem to pass their virus, particularly mothers to daughters, 01:09:53.420 --> 01:09:56.929 through their chromosomes. So there are situations, 01:09:56.929 --> 01:10:00.300 but that's the exception, luckily. But it's-- 01:10:00.300 --> 01:10:04.500 these are the tougher (cases) to deal with. [Question asked] So the question is very clever. So the same 01:10:04.500 --> 01:10:05.929 way we can prevent-- 01:10:05.929 --> 01:10:11.909 and that is true--we can prevent HIV-infected mothers from giving HIV to their babies. 01:10:11.909 --> 01:10:15.759 Can something like that be done for mothers with CFS? 01:10:15.760 --> 01:10:19.800 Unfortunately, the drugs 01:10:19.800 --> 01:10:22.540 can damage the baby, theratogenic, so that 01:10:22.540 --> 01:10:25.890 makes it very hard to justify doing it with our 01:10:25.890 --> 01:10:30.650 proper study setting. So that makes it very hard. But 01:10:30.650 --> 01:10:33.670 I was at a meeting last night in 01:10:33.670 --> 01:10:36.710 in Washington, with a patient who has 01:10:36.710 --> 01:10:40.730 her daughter with it, and she once--her daughter, 01:10:40.730 --> 01:10:44.919 through the treatment that we did, went back to complete normality after years of 01:10:44.920 --> 01:10:48.940 having the illness. And they are now desperate that she got married, 01:10:48.940 --> 01:10:52.990 newly married, and they want to have a baby, et cetera. How do you do it? 01:10:52.100 --> 01:10:55.550 At this point there is nothing we can do. Unfortunately. 01:10:55.550 --> 01:10:59.140 [Question asked] Two points: one is, do we have ways to 01:10:59.140 --> 01:11:03.469 standardize what we are doing, so other physicians can have easy access 01:11:03.469 --> 01:11:08.380 to doing those steps, and following the--the answer is yes. 01:11:08.380 --> 01:11:11.659 And we talk to other physicians who are-- 01:11:11.659 --> 01:11:15.230 So many physicians had doing this now, nationwide, 01:11:15.230 --> 01:11:19.590 and sometimes the patients, after they have been on the waiting list, they come to us 01:11:19.600 --> 01:11:22.190 after they have been treated. And we're just fine-tuning the issues. 01:11:22.190 --> 01:11:25.860 so we do have standard formats 01:11:25.860 --> 01:11:29.159 that we give out to physicians. 01:11:29.159 --> 01:11:32.509 And I think that I can say that, because 01:11:32.510 --> 01:11:37.190 it's legal, and medically viable, we can actually put those protocols in 01:11:37.190 --> 01:11:38.629 the website as well, 01:11:38.630 --> 01:11:42.110 because none of the drugs that we personally, 01:11:42.110 --> 01:11:45.710 we at the clinic are using, none of them are experimental. 01:11:45.710 --> 01:11:49.699 They are all FDA-approved. And as you know, 01:11:49.699 --> 01:11:54.849 any physician has the freedom to use any drug that is approved by the FDA for any 01:11:54.850 --> 01:11:56.890 other indication that is reasonable. 01:11:56.890 --> 01:12:01.179 so that is not illegal. And we put those protocols 01:12:01.179 --> 01:12:04.280 in the website so physicians can download them. 01:12:04.280 --> 01:12:07.730 But in the meantime, they can call us, and we give them out, and we talk to the 01:12:07.730 --> 01:12:11.610 physicians as well. Regarding the equilibrium-- 01:12:11.610 --> 01:12:14.809 That is a drug 01:12:14.810 --> 01:12:18.110 that comes from China, so we don't prescribe it because we we cannot 01:12:18.110 --> 01:12:23.259 guarantee what--how many milligrams and the purity of the drug, 01:12:23.260 --> 01:12:27.320 but if the suspicion is that other kinds of viruses called 01:12:27.320 --> 01:12:31.920 entero- or echoviruses are behind it, we highly suggest the patient to 01:12:31.920 --> 01:12:35.280 consult Dr. Chia in Southern California, because he 01:12:35.280 --> 01:12:39.120 really is the one with the expertise, and that's his baby, 01:12:39.120 --> 01:12:42.519 and I totally trust that what he has found is valid. 01:12:42.520 --> 01:12:46.489 But we don't have the expertise with the administration of the drug. 01:12:46.489 --> 01:12:47.500 Thank you. [Applause]