disulfiram

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Roxy
Berichten: 6387
Lid geworden op: Wo 29 Okt 2014, 12:14

Re: disulfiram

Berichtdoor Roxy » Ma 26 Okt 2020, 12:58

Henriëtte schreef:Disulfiram: Ein Test zur Symptomreduktion bei Patienten mit zuvor behandelter Lyme-Borreliose ;
Wissenschaftler entdeckten kürzlich, dass Disulfiram im Labor wirksam ist, um das zu töten Mikroben, die Lyme-Borreliose verursachen. Disulfiram ist allgemein bekannt als "Antabuse

Die meisten Bemerkenswert ist, dass Disulfiram nicht nur die aktiv replizierende Lyme wirksam abtötete Bakterien (dh diejenigen, die typischerweise durch mehrere Antibiotika abgetötet werden), aber auch die relativ ruhende oder ruhende Lyme-Bakterien (diese werden als "arzneimittelverträgliche Persistenten" bezeichnet) - Diese letzteren Spirochäten sind diejenigen, die für die Entwicklung der chronischen Lyme verantwortlich sein können Krankheitssymptome.

https://ichgcp.net/de/clinical-trials-r ... CT03891667

Ilads 2020
11 september 2020
Disulfiram In The Treatment Of Lyme & Babesiosis - Retrospective Review Of First 3 Years' Experience In One Medical Practice
Kenneth B Liegner, MD
BACKGROUND
High throughput screening found disulfiram more potent versus Bb than conventionally recommended antibiotics in vitro(1). This prompted off-label use of this agent as previously reported (2).

AIMS:
We report our subsequent experience with disulfiram between 3-15-2017 and 3-15-2020.

PATIENTS & METHODS:
Patients were evaluated in the ordinary course of clinical care. In addition to standard treatment methods disulfiram was mentioned as a possible option for the treatment of Lyme disease. For those preferring disulfiram, full discussion was held regarding potential risks, potential benefits and considerable uncertainties with novel application of this agent. 4 of 71 patients were 'lost to follow-up' resulting in 67 evaluable patients.

RESULTS:
Of 67 evaluable patients:
13 of 33 patients (39%) who completed one or two courses of high-dose disulfiram (> or = 4 mg/kg/day) were able to enjoy 'enduring remission' defined as remaining clinically well for > or = 6 months without further anti-infective treatment.
62 of 67 patients (92.5%) endorsed net benefit from the received course or courses of disulfiram, combining the low dose group (<4mg/kg/day), the high dose group and the 'cross-over' group.
5 of 67 patients (7.5%) reported either no benefit or unclear benefit from application of disulfiram. It is unclear whether a low dose regimen can yield 'enduring remission' after discontinuation of treatment.
10 of 67 patients (15%) reported development of paresthesias thought consistent with disulfiram-induced peripheral neuropathy. These symptoms completely or substantially resolved over weeks to months with only minimal if any residua in 7 of 10. Mild to moderate residual persisted in 3 of 10.
21 of 67 patients (31%) exhibited emotional instability ranging from hypomania to anxiety and/or depression. Mood disturbance resolved within days to weeks in all patients with cessation of disulfiram although a few required psychiatric intervention.
10 of 67 patients (15%) exhibited mild to moderate hepatic transaminitis which required cessation of treatment in 2 patients. Transaminitis fully resolved in all cases.

CONCLUSIONS:
Disulfiram monotherapy is useful in the treatment of Lyme disease. Regular laboratory monitoring and close clinical follow-up is necessary. Dosages of 4-5 mg/kg/day for 6-12 weeks appear to be optimal for attempting to achieve 'enduring remission' while minimizing adverse effects. Dosages as low as 0.06 - 2 mg/kg/day for indeterminate durations also conferred benefit with minimal adverse effects. An individualized and flexible approach with shared decision-making is particularly suitable in the use of this agent
Het betreft een kleine patiëntengroep van 67 patiënten. Het is onduidelijk of de resultaten blijvend zijn na de beëindiging van de behandeling.
In Lyme patiëntengroepen melden er mensen dat zij moeten stoppen met de behandeling omdat er ernstige bijwerkingen/klachten (neuropathie, hartproblemen, psychische klachten/psychose) ontstaan, de periode van 6-12 weken behandelen niet wordt gehaald, het middel niet goed wordt verdragen bij lage en hoge doseringen, sommigen op de spoed (SEH) in het ziekenhuis terecht zijn gekomen, dat de leverwaarden erg hoog worden. Farmacotherapeutisch Kompas - Disulfiram; Bron https://www.farmacotherapeutischkompas. ... jwerkingen

Frontiers in Medicine
20 April 2020
Alain Trautmann1*, Hugues Gascan2 and Raouf Ghozzi3* - 'Potential Patient-Reported Toxicities With Disulfiram Treatment in Late Disseminated Lyme Disease'; Bron https://www.frontiersin.org/articles/10 ... 00133/full
..However, in a recent talk at the 2019 ILADS Symposium, Dr. Liegner presented data on 30 Lyme Disease patients that he had treated with DSF. In 18 of them, DSF provoked either peripheral neuropathies or psychiatric problems, or both.

..It is necessary to understand why DSF toxicity appears particularly severe and frequent in patients with Lyme Disease, and to rapidly explore the reasons for such DSF toxicity in Lyme Disease animal models. Until we have the first answers to this question, it would be premature to consider DSF as the new miracle molecule for patients suffering from late disseminated Lyme Disease..

..The conclusions are: 13 out of 16 patients experienced DSF-induced toxic or side effects, mainly concerning the nervous system (neuropathies, headaches, dizziness, difficulty of concentration and expression, sleep disturbance, general pain increase, increase in general fatigue). Several patients reported a more specific increase in their osteo-articular pains, nausea or intestinal disorders..

..However, some patients, who had already experienced Jarisch Herxheimer reactions before, reported that some of the reactions encountered with DSF treatment were clearly of a different nature. Collectively, these observations suggest that patients with persistent Lyme Disease are more sensitive to the toxicity of DSF than people who have been treated for alcohol dependence, and that in these patients, DSF-induced toxicities are not all related to Jarish Herxeimer reactions..
~ I may not be there yet, but I'm closer than I was yesterday ~
~ The people who are meant to be in your life are the ones who know how to gently wait for you to heal ~
~ So encourage each other and build each other up - Positive connections ~

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Roxy
Berichten: 6387
Lid geworden op: Wo 29 Okt 2014, 12:14

Re: disulfiram

Berichtdoor Roxy » Di 12 Okt 2021, 22:58

Onderzoek
Initial Study - 'Disulfiram: A Test of Symptom Reduction Among Patients With Previously Treated Lyme Disease' by Brian A Fallon; Bron https://clinicaltrials.gov/ct2/show/NCT03891667
De resultaten van de pilot-studie (voorlopige studie ter verkenning) met 24 personen zijn uitgesteld naar 31 maart 2022.
..The investigators propose therefore a small 14-week randomized placebo-controlled pilot study enrolling 24 patients with persistent symptoms despite prior antibiotic treatment for Lyme disease (known as Post-treatment Lyme Disease Syndrome). Among the 24 disulfiram-treated patients, half will get 8 weeks of disulfiram and the other half will get a shorter duration of disulfiram for 4 weeks followed by 4 weeks of matching placebo. After week 8, patients will be off pills for 2 weeks for the primary week 10 evaluation and then for another 4 weeks for the week 14 follow-up evaluation. This will be a double-blinded study; neither physician nor patient will know which treatment group the patient is assigned to.

With this initial study, the investigators will be able to evaluate the side effects, tolerability and initial signs of the effectiveness of disulfiram in reducing symptoms among the 24 patients assessed. The results of this study will guide the investigators regarding whether a larger definitive randomized trial should be conducted and which treatment schedule is optimal..

Lymedisease.org
23 november 2020
By Dr Daniel A. Kinderlehrer MD (internist) - Patients can respond very differently to disulfiram. Be cautious (over 100 patients); Bron https://www.lymedisease.org/kinderlehre ... m-caution/

Lymedisease.org
8 februari 2021
Kinderlehrer videos discuss disulfiram treatment, mast cell, and more; Bron https://www.lymedisease.org/kinderlehre ... mast-cell/

8 oktober 2021
dr R.H is bezig met nieuw klinisch onderzoek waarbij er met een lagere dosering wordt behandeld; Bron https://www.facebook.com/drrichardhorowitz/
..We are now doing a new clinical trial combining lower dose DSF with higher dose pulsed dapsone x 4 days (neither DSF or dapsone has significant effects on the microbiome based on clinical experience) or trialing pulsed high dose dapsone. So far, the early clinical results are encouraging. Certain resistant patients are showing significant improvement. I plan on publishing the results at the beginning of next year once enough patients have enrolled and I see the long term efficacy. Stay tuned, but in my world, we are getting closer and closer to finding a durable regimen for long term remission..
~ I may not be there yet, but I'm closer than I was yesterday ~
~ The people who are meant to be in your life are the ones who know how to gently wait for you to heal ~
~ So encourage each other and build each other up - Positive connections ~

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Roxy
Berichten: 6387
Lid geworden op: Wo 29 Okt 2014, 12:14

Re: disulfiram

Berichtdoor Roxy » Vr 15 Okt 2021, 22:04

Lyme Disease.org
5 oktober 2021
LYME SCI: My re-cap of recent LDA/Columbia Lyme conference; Bron https://www.lymedisease.org/lda-columbi ... onference/
On October 2, I attended the 21st annual scientific conference put on by the Lyme Disease Association and Columbia University’s Vagelos College of Physicians & Surgeons. The virtual event was entitled Lyme & Other Tick-Borne Diseases: Research for a Cure.
Disulfiram
..Dr. Fallon made a point of stating the use of disulfiram is experimental and not currently approved for Lyme disease..
Een experimentele of verkeerde behandeling kan érg schadelijk zijn voor de gezondheid. Patiënten kunnen als gevolg van de behandeling ernstige langdurige (of blijvende) klachten (neurologische en of psychische) krijgen en of blijvende schade aan de darmen en de werking van het afweersysteem (immuunsyteem) krijgen. Mensen worden in dat geval niet beter maar zieker.

Opmerkelijk is dat dr R.H bezig is met nieuw klinisch onderzoek waarbij er met een lage dosering wordt behandeld; Bron https://www.facebook.com/drrichardhorowitz/
8 oktober2021:..We are now doing a new clinical trial combining lower dose DSF with higher dose pulsed dapsone x 4 days (neither DSF or dapsone has significant effects on the microbiome based on clinical experience) or trialing pulsed high dose dapsone. So far, the early clinical results are encouraging. Certain resistant patients are showing significant improvement.
I plan on publishing the results at the beginning of next year once enough patients have enrolled and I see the long term efficacy. Stay tuned, but in my world, we are getting closer and closer to finding a durable regimen for long term remission..
Forbes
26 februari 2020
Tipping Point: The Resistance Is Gaining In The Lyme Wars; Bron https://www.forbes.com/sites/marybethpf ... 352ee45d5a
Fred Verdult, a longtime activist who was knighted for his work in The Netherlands, exemplifies the problem and progress. He takes one pill daily for HIV infection and has never been ill from AIDS. He has been disabled by, and treated with dozens of pills daily, for Lyme disease. “The contrast with Lyme couldn’t be greater,” he wrote in answer to my survey.

He nonetheless sees a corner turning, in particular in the use of repurposed drugs; Bron https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627205/ that are helping patients like him. “It will take years,” he told me. “But the final result is very clear: In 2030, Lyme and other tick-borne diseases will be considered as normal diseases.”
~ I may not be there yet, but I'm closer than I was yesterday ~
~ The people who are meant to be in your life are the ones who know how to gently wait for you to heal ~
~ So encourage each other and build each other up - Positive connections ~

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Roxy
Berichten: 6387
Lid geworden op: Wo 29 Okt 2014, 12:14

Re: disulfiram

Berichtdoor Roxy » Do 12 Mei 2022, 22:24

8 oktober 2021
dr R.H is bezig met nieuw klinisch onderzoek waarbij er met een lagere dosering wordt behandeld; Bron https://www.facebook.com/drrichardhorowitz/
..We are now doing a new clinical trial combining lower dose DSF with higher dose pulsed dapsone x 4 days (neither DSF or dapsone has significant effects on the microbiome based on clinical experience) or trialing pulsed high dose dapsone. So far, the early clinical results are encouraging. Certain resistant patients are showing significant improvement. I plan on publishing the results at the beginning of next year once enough patients have enrolled and I see the long term efficacy. Stay tuned, but in my world, we are getting closer and closer to finding a durable regimen for long term remission..
Preprint (This version is not peer-reviewed)
Publicatie 29 april 2022
Case study - 'Efficacy of Short-Term High Dose Pulsed Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Literature Review' by Richard I. Horowitz and Phyllis R. Freeman; Bron https://www.preprints.org/manuscript/20 ... Tq0uMRfNBA
Bron https://www.facebook.com/drrichardhorowitz/ 4 mei 2022:..I just submitted for peer-review (last week), my new article on high dose pulsed dapsone combination therapy (HDDCT) for the treatment of CLD/PTLDS. Early results are very encouraging regarding having discovered a short term oral, generic treatment that is effective for not only Lyme, but some individuals suffering from Babesia and Bartonella, in the 50% who have failed double dose dapsone combination therapy, ie DDDCT.
If proven true, which will require much larger numbers of patients in a RCT, combining the results of this study with the study on DDDCT, it would mean approximately 66% of individuals could go into long term remission with CLD/PTLDS from 9-10 weeks of an antibiotic protocol using a high dose persister drug like dapsone with multiple biofilm agents, while addressing all abnormalities on the 16 point MSIDS map..
4. Discussion
..Our study has several limitations, as outlined below. Our cohort was too small to determine if adding disulfiram to dapsone prior or during HDDCT and using DSF in different dosages and lengths of treatment, significantly affected treatment outcomes. Larger numbers of patients in well-controlled, randomized studies will be needed to evaluate the efficacy of HDDCT after using DDDCT with or without DSF in those suffering from chronic Lyme/PTLDS, with or without Bartonellosis and babesiosis. Our follow-up and operational definition of remission was also evaluated at a three-month interval, as some patients were just finishing a third course of HDDCT, so efficacy and relapse rates long term is unknown. The efficacy of HDDCT was similarly evaluated in a very ill patient population with multiple overlapping medical problems, as noted in Figure 1, where up to 18 different variables on the MSIDS map were found to be present. It is possible efficacy will vary and potentially improve, in a cohort of patients who are not ill for 20+ years with so many overlapping sources of inflammation.

As an example, mold toxicity, with or without multiple chemical sensitivity, was found in 9/25 patients (36%), and mycotoxin exposure has been linked to Chronic Fatigue Syndrome (CFS/ME) [142], where some individuals with mold exposure had gliotoxins known to be immunosuppressive [143], potentially interfering with treatment response. POTS/dysautonomia was found in 7/25 patients (28%). Symptoms of POTS include fatigue, dizziness, palpitations, anxiety, and cognitive difficulties [144] [22] and may have influenced treatment results. One patient with mercury toxicity (blood level greater than 25 μg/L, upper range less than 10) noted significant help with resistant tinnitus, fatigue and cognition using HDDCT, but was simultaneously being chelated for his elevated level of mercury with low dose dimercaptosuccinic acid (DMSA) [145], so the treatment effects may have coincided. Multiple overlapping variables on the MSIDS map in this patient population thereby makes it difficult to get a full picture of the efficacy of HDDCT, and these variables will need to be accounted for in future studies.

We also did not regularly evaluate patients for the presence of other tick-borne infections including hard tick relapsing fever, Borrelia miyamotoi, nor exposure to the deer tick (Powassan) virus, which are emerging tick-borne infections [146] [147], which potentially can influence morbidity. Despite these challenges however, HDDCT appears to be a promising novel therapy, which should be explored with scientific rigor and randomized, controlled trials, as few effective options are now available for those suffering from CLD/PTLDS..
Een interessante case study over een kleine patiëntengroep (3 patiënten). R.H geeft daarbij ook duidelijk aan dat er vervolgens klinisch onderzoek nodig is met grote groepen mensen-patiënten. Dubbelblind gerandomiseerd placebo gecontroleerd onderzoek (Randomized Controlled Trial (RCT)) is nodig om het gestelde te kunnen bevestigen.
De behandeling is voorlopig een experimentele behandeling waar de huisartsen, de medisch specialisten en de Lyme artsen in Nederland niet mee kunnen werken. Het is eerst afwachten of er in de nabije toekomst aanvullend klinisch onderzoek zal worden gedaan en wat de resultaten daarvan zullen zijn.

Disulfiram - actuele paperback Lymeziekte 2021; Bron https://www.biomaatschappij.nl/product/lymeziekte/ en een gratis pdf van het boekje; Bron https://www.biomaatschappij.nl/wp-conte ... DF-DEF.pdf
..Meer recentelijk is er bij een kleine groep artsen interesse ontstaan om chronische lyme te behandelen met disulfiram, een geneesmiddel dat wordt ingezet bij de behandeling van alcoholverslaving. Los van de discussie over wat nou precies onder de term chronische lyme wordt verstaan (zie 3.2), is ook hiervan niet aangetoond dat het werkt. Wel wordt hier nog verder onderzoek naar gedaan. Met het oog op recente beschrijvingen van ernstige (en soms langdurige) bijwerkingen van patiënten die dit middel gebruiken ter verlichting van hun klachten, lijkt het verstandig de resultaten van dergelijk onderzoek af te wachten alvorens dit in de praktijk toe te passen..
Hetzelfde geldt voor Dapson. Farmacotherapeutisch Kompas - Dapson (indicaties: Lepra en Dermatitis herpetiformis (ziekte van Duhrin)); Bron https://www.farmacotherapeutischkompas. ... n/d/dapson
~ I may not be there yet, but I'm closer than I was yesterday ~
~ The people who are meant to be in your life are the ones who know how to gently wait for you to heal ~
~ So encourage each other and build each other up - Positive connections ~

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Roxy
Berichten: 6387
Lid geworden op: Wo 29 Okt 2014, 12:14

Re: disulfiram

Berichtdoor Roxy » Vr 13 Mei 2022, 16:10

ASM Journals
Publicatie 25 april 2022
Minireview - 'Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes' by Felipe C. Cabello, Monica E. Embers, Stuart A. Newman, Henry P. Godfrey; Bron https://journals.asm.org/doi/10.1128/mbio.03440-21
Bron https://www.facebook.com/drrichardhorowitz/ 30 april 2022 R.H: 'Monica Embers discusses persister mechanisms in a new published article below, yet there is no mention of dapsone's effect on resistant biofilm forms of Bb?
And questioning the mechanisms behind PTLDS even though we did a study in 200 patients looking at the different overlapping medical problems? See the articles below. These are peer-reviewed studies. I just don't get it.

Horowitz, R.I.; Freeman, P.R. Efficacy of Double-Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Dis-ease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Retro-spective Chart Review. Antibiotics 2020, 9, 725. https://doi.org/10.3390/antibiotics9110725

Horowitz, R.I., Murali, K., Gaur, G. et al. Effect of dapsone alone and in combination with intracellular antibiotics against the biofilm form of B. burgdorferi. BMC Res Notes 13, 455 (2020). https://doi.org/10.1186/s13104-020-05298-6
https://bmcresnotes.biomedcentral.com/a ... 20-05298-6

Horowitz, R.I.; Freeman, P.R. Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2. Healthcare 2018, 6, 129.
https://www.ncbi.nlm.nih.gov/pubmed/30400667 '
Opmerkelijk dat R.H het niet begrijpt. Ook in Amerika zal menig huisarts, medisch specialist, Lyme arts, wetenschapper/onderzoeker niet achter het behandel protocol staan met de gebruikte experimentele medicatie als 'disulfiram en dapson' (ernstige bijwerkingen) en de vele supplementen (waar evenmin goede medische en wetenschappelijke onderbouwingen en publicaties van zijn). De behandelingen worden niet vergoed en de gemiddelde Amerikaan zal de kostbare behandelingen (€10.000 - €20.000 (per jaar)) niet kunnen betalen.

De enkele en kleine studies waar naar wordt verwezen zijn onvoldoende om als medisch én wetenschappelijk bewijs te kunnen gelden.
De vraag lijkt al beantwoord.. R.H geeft zelf immers al duidelijk aan dat er vervolgens klinisch onderzoek (Randomized Controlled Trial (RCT)) nodig is met grote groepen mensen-patiënten. Dubbelblind gerandomiseerd placebo gecontroleerd onderzoek (Randomized Controlled Trial (RCT)) is nodig om het gestelde te kunnen bevestigen. Klinisch onderzoek vraagt veel tijd (jaren) en kost veel geld.
..If proven true, which will require much larger numbers of patients in a RCT..

..Our study has several limitations, as outlined below. Our cohort was too small to determine if adding disulfiram to dapsone prior or during HDDCT and using DSF in different dosages and lengths of treatment, significantly affected treatment outcomes. Larger numbers of patients in well-controlled, randomized studies will be needed to evaluate the efficacy of HDDCT after using DDDCT with or without DSF in those suffering from chronic Lyme/PTLDS, with or without Bartonellosis and babesiosis..
~ I may not be there yet, but I'm closer than I was yesterday ~
~ The people who are meant to be in your life are the ones who know how to gently wait for you to heal ~
~ So encourage each other and build each other up - Positive connections ~


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