Head-down tilt reduces the heart rate in postural tachycardia syndrome in acute setting: a pilot study

Abstract:

Background: Reduced preload and thoracic blood volume accompany postural tachycardia syndrome (POTS). Head-down tilt (HDT) increases both preload and intrathoracic blood volume. The objective of this study was to assess the safety and efficacy of HDT in POTS in acute settings.

Methods: This retrospective study evaluated POTS patients. Analyzed data included heart rate, blood pressure, cerebral blood flow velocity (CBFv) in the middle cerebral artery, and capnography. The baseline supine hemodynamic data were compared with the data obtained at the second minute of the -10° HDT. A linear mixed-effects model was used to assess the effect of HDT on hemodynamic variables.

Results: The HDT was explored in seven POTS patients and an additional seven POTS patients without HDT served as controls. In the HDT arm, four POTS patients had overlapping diagnoses of myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) and one patient had comorbidity of post-acute sequelae of SARS-CoV-2 infection (PASC). HDT lowered heart rate by 10% and increased end-tidal CO2 by 8%. There was no change in other cardiovascular variables.

Conclusions: In the acute setting, HDT is safe. HDT reduces the heart rate presumably by modulating baroreflex by enhancing preload and stroke volume, which in turn increases thoracic blood volume with a net effect of parasympathetic cardiovagal activation and/or sympathetic withdrawal. This pilot study provides a foundation to proceed with longitudinal studies exploring the long-term effect of repetitive HDT in conditions associated with preload failure such as POTS, ME/CSF, and PASC.

Source: Novak P. Head-down tilt reduces the heart rate in postural tachycardia syndrome in acute setting: a pilot study. Neurol Sci. 2023 Nov 3. doi: 10.1007/s10072-023-07153-5. Epub ahead of print. PMID: 37919442. https://pubmed.ncbi.nlm.nih.gov/37919442/

‘We have no services for you… so you have to make the best out of it’: A qualitative study of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients’ dissatisfaction with healthcare services

Abstract:

Introduction: People should have access to healthcare services that are effective, safe and secure, patient-centred, and coordinated and continuous. One group that has consistently reported negative experiences and feels dissatisfied with services are patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). The objective of this study was to develop a deeper understanding of the experiences of dissatisfaction among ME/CFS patients and explore the reasons for such dissatisfaction.

Methods: We conducted in-depth interviews with 48 people from 24 households (comprising patients and family members), providing insight into the experiences of 37 ME/CFS sufferers in Norway. The participants were purposively sampled and included persons of different ages, genders, time since having the condition (3-30 years), and severity.

Results: Four main themes were developed: (1) ‘Nonexistent services’ cover patients’ experience that healthcare services had nothing to offer them after receiving their ME/CFS-diagnosis. (2) ‘Nonpersonalised services’ documents experiences where patients did receive services, which in theory was appropriate for relieving a specific health problem, but in practice were experienced as inappropriate because they were not adapted to the patient’s need. (3) ‘Slow services’ address patients’ experience of getting services too late (or too little) to be useful. (4) ‘Wrong services’ comprise patients’ experiences of being offered and/or ‘forced’ to accept services that they felt were inappropriate for their health problems.

Conclusions: Providers’ lacking knowledge of the condition and lack of precise recommendations for follow up may partly explain unsatisfactory experiences. Providers’ belief (or disbelief) in the condition could furthermore influence caregiving. Also, systemic issues in the healthcare sector, like high workloads and bureaucracy, can negatively affect care provision. Finally, users’ unsatisfactory experiences may also be due to a lack of patient involvement in the design of such services. Further research should investigate how patients can be involved in service design, and also providers’ perspectives on caregiving and the barriers they experience for providing high-quality care.

Patient or public contribution: The ME-patient organisation suggested research topics to the call from which this study got funding. Patients and caregivers provided feedback during analysis and interpretation of data.

Source: Melby L, Nair RD. ‘We have no services for you… so you have to make the best out of it’: A qualitative study of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients’ dissatisfaction with healthcare services. Health Expect. 2023 Oct 31. doi: 10.1111/hex.13900. Epub ahead of print. PMID: 37905602. https://onlinelibrary.wiley.com/doi/10.1111/hex.13900 (Full text)

Fatigue in post COVID-19 patients: the P4O2 COVID-19 study

Abstract:

Background: Some patients do not fully recover after COVID-19 and have symptoms occurring 3 months after acute illness, lasting for >2 months, defined as post COVID-19. Fatigue seems most present in post COVID-19 and part of the patients might develop symptoms similar to chronic fatigue syndrome.

Aim: To determine the occurrence of fatigue and other symptoms in post COVID-19 patients.

Methods: In the prospective P4O2 COVID-19 cohort, post COVID-19 patients aged 40-65 years were recruited from outpatient post-COVID clinics in 5 Dutch hospitals between May 2021-September 2022. At 3-6 months post-COVID, patients completed the Fatigue Severity Scale (FSS). If the FSS score was ≥4 (the cut-off for severe fatigue), patients also completed the DePaul Symptom Questionnaire version 2 (DSQ-2). The FSS ranges from 1-7 and a higher score means more fatigued. The DSQ-2 rates frequency and severity of 79 symptoms on a 5-point Likert scale. Binary thresholds (if scored ≥2 on both severity and frequency, the threshold is met and the symptom is present) were calculated.

Results: The mean age of the 78 included patients was 53.9±6.2 and 51.7% were male. Median (IQR) FSS score was 5.6 (4.2-6.3) and 66 patients (84.6%) had a score ≥4. According to the DSQ-2 (n=61), patients reported a median (IQR) of 16 (8-23) symptoms. The majority of the patients experienced fatigue (85%). Furthermore, post-exertional malaise (PEM) (40%), sleep-related problems (37%), pain (21%) and neurocognitive problems (23%) were frequently reported.

Conclusion: The occurrence of severe fatigue 3-6 months after COVID-19 was 84.6% in our cohort. Patients with severe fatigue also frequently reported PEM, sleep related problems, pain and neurocognitive problems.

Source: Merel E.B. Cornelissen, Lizan D. Bloemsma, Nadia Baalbaki, Somayeh Bazdar, Jelle M. Blankestijn, Inés Beekers, Rosanne J.H.C.G. Beijers, Joop P. Van Den Bergh, Debbie Gach, J.J. Miranda Geelhoed, Sebastiaan Holverda, Laura Houweling, John J. Jacobs, Renée Jonker, Ivo Van Der Lee, Paulien M.A. Linders, Lieke C.E. Noij, Esther J. Nossent, Marianne A. Van De Pol, Daphne W. Schaminee, Annemie M.W.J. Schols, Lisanne T. Schuurman, Brigitte Sondermeijer, Anouk W. Vaes, Els J.M. Weersink, Yolanda De Wit-Van Wijck, Martijn A. Spruit, Anke H. Maitland-Van Der Zee. Fatigue in post COVID-19 patients: the P4O2 COVID-19 study. European Respiratory Journal 2023 62: PA4574; DOI: 10.1183/13993003.congress-2023.PA4574 https://erj.ersjournals.com/content/62/suppl_67/PA4574.abstract

Repetitive Transcranial Magnetic Stimulation Ameliorates Symptoms in Patients with Myalgic Encephalomyelitis (Chronic Fatigue Syndrome)

Highlights:

• Repetitive transcranial magnetic stimulation (rTMS) was applied to the brain in patients with myalgic encephalomyelitis.
• After therapy, the restriction of activity of daily living was ameliorated in most patients.
• rTMS alleviated various symptoms, especially orthostatic intolerance and disequilibrium.

Abstract:

Background: Central nervous system dysfunction has been postulated to cause debilitating symptoms in patients with myalgic encephalomyelitis (ME) (originally called “chronic fatigue syndrome”). Repetitive transcranial magnetic stimulation (rTMS) is a newly developed neuromodulatory procedure and has been suggested to facilitate the cortical neural activity.

Methods: This study enrolled 30 patients with ME (7 men and 23 women) with a mean age of 39±12 years, who received rTMS treatment of both the left dorsolateral prefrontal cortex and the left primary motor area in the brain. The performance status score (0–9) for restricting activities of daily living, orthostatic intolerance (OI) during a 10-min standing test, neurologic disequilibrium diagnosed as unstable standing with their feet together and eyes closed, neuropathic pain or fibromyalgia, and muscle weakness were compared before and after treatment.

Results: After therapy, favorable effects were observed with a decrease in performance status score or index for restriction of activities of daily living of ≥2 points in 20 patients (67%). OI with the inability to complete the 10-min standing test was resolved in 10 (83%) out of 12 patients, and disequilibrium was resolved in 15 (88%) out of 17 patients. Neuropathic pain or fibromyalgia was attenuated in seven (70%) out of 10 patients. Muscle weakness with grip power of <10 kg was resolved in two (50%) out of four patients. No untoward effects were encountered in all the study patients.

Conclusion: The treatment with rTMS is effective in alleviating various symptoms, especially OI and disequilibrium, and in improving the activities of daily living in patients with ME.

Source: Kunihisa Miwa, Yukichi Inoue. Repetitive Transcranial Magnetic Stimulation Ameliorates Symptoms in Patients with Myalgic Encephalomyelitis (Chronic Fatigue Syndrome). Published: October 30, 2023 DOI:https://doi.org/10.1016/j.ibneur.2023.10.008 https://www.sciencedirect.com/science/article/pii/S2667242123022777 (Full text)

Investigation into the Plasma Proteome Signature in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background: ME/CFS is a complex disease with unclear etiology. Current diagnostic criteria lack objective laboratory measures.

Aims: This study aimed to investigate the plasma proteomic profile of ME/CFS patients and determine any differentially expressed proteins compared to controls.

Methods: Plasma samples obtained from 19 ME/CFS patients and 9 controls underwent analysis (Somalogic, Inc, CO). The ME/CFS patients met the National Academy of Medicine criteria for the disease. Samples were collected from a mixed venous compartment. Statistical analysis and a Mixed Graphical Model were used to identify candidate biomarker.

Results: Among ~7000 proteins detected, ~400 were differentially expressed between patients and controls (False Discovery Rate<0.05 and Absolute Fold Change ≥1.5). Selectin E (SELE), ATP Synthase Subunit F6 (ATP5PF), and Transcobalamin 2 (TCN2) were identified as top candidates. A classifier of these proteins in pulmonary artery blood of patients were distinguishable from controls (AUC =0.99).

Conclusion: The study highlighted potential biomarkers for ME/CFS, the top candidates of which are involved in inflammation, cellular energy metabolism, and Vitamin B12 transport. The plasma proteomic signature identifies ME/CFS from normals and suggests that the disease’s pathophysiology is driven by abnormalities of aerobic metabolism, vascular dysregulation, and Vitamin B12 metabolism.

Source: Johanna Squires, Sarra Al-Zayer, Peng Li, Wenzhong Xiao, David Systrom. Investigation into the Plasma Proteome Signature in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). European Respiratory Journal Sep 2023, 62 (suppl 67) PA2960; DOI: 10.1183/13993003.congress-2023.PA2960 https://erj.ersjournals.com/content/62/suppl_67/PA2960.abstract

Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome using hydrogen gas: four case reports

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue and malaise that persist for more than 6 months with neuropsychiatric symptoms, including slight fever, headache, weakness, impaired thinking, and depression.[1,2] The onset and severity of these symptoms vary and reduce the quality of life as well as social, occupational, and personal activities of those affected, with some becoming bedridden.[1,2] The number of ME/CFS patients in the United States is estimated to be between 836,000 and 2.5 million.[3]

Although it currently remains unclear whether there are objective and biological abnormalities in ME/CFS, recent neuroimaging, blood marker analyses, and energy metabolism and mitochondrial studies detected these abnormalities in ME/CFS patients.[4] ME/CFS may be caused by the activation of the immune system, both within and outside the brain, which induces the release of inflammatory cytokines. ME/CFS is presumed to cause abnormalities in the central and autonomic nervous systems, systemic energy metabolism, and immune system and also involve oxidative and nitrosative stress.[4,5,6] Dysfunctions in systemic energy metabolism may be related to abnormalities in the structure and function of mitochondria.[7,8,9,10]

Molecular hydrogen (H2) is a gaseous molecule that selectively scavenges reactive oxygen and nitrogen species with strong oxidizing power, namely, hydroxyl radicals (·OH) and peroxynitrite, respectively.[11,12] H2 easily crosses the blood-brain barrier and biological membranes, reaches mitochondria, and protects cells from ·OH-induced cell damage.[11,12] A recent literature review revealed that H2 attenuated acute or chronic fatigue in animals and healthy subjects.[13] We also reported that the anti-fatigue effects of H2 involved the protection of mitochondria, which may also ameliorate the pathogenesis of ME/CFS.[13] Therefore, we conducted this case study to test this hypothesis by examining the efficacy of H2 gas inhalation in four patients with ME/CFS.

Source: Hirano, Shin-ichi*; Ichikawa, Yusuke; Sato, Bunpei; Takefuji, Yoshiyasu; Satoh, Fumitake. Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome using hydrogen gas: four case reports. Medical Gas Research 14(2):p 84-86, June 2024. | DOI: 10.4103/2045-9912.385441 https://journals.lww.com/mgar/fulltext/2024/14020/successful_treatment_of_myalgic.7.aspx (Full text)

Exercise capacity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) treated with long-term pyridostigmine

Abstract:

Background: The pathophysiology underlying exertional intolerance in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains poorly understood. Previously, a single-dose of 60 mg pyridostigmine, a reversible acetylcholinesterase inhibitor, was found to acutely improve aerobic capacity (Joseph, P. et al. Chest 2022; 162:1116–26).

Aims: To build upon these prior findings, this study aimed to evaluate the long-term effect (>1 month) of pyridostigmine treatment on exercise intolerance in ME/CFS.

Methods: Between 2017-2022, patients who met the National Academy of Medicine criteria for ME/CFS, and had a minimum of two clinical, constant load, submaximal exercise tests (Shape Medical System, MN) were evaluated. Patients who began pyridostigmine after their baseline test were considered the treatment group. Measurements were taken at baseline (T0) and most recent follow-up (T1).

Results: At the follow-up evaluation (690 ± 547 days), the treatment group (n=37, dose range: 24-360mg/d) demonstrated a significant increase in oxygen uptake efficiency slope (OUES) (T0: 1.82 ± 0.56, T1: 1.98 ± 0.53; p=0.044) and pulmonary vascular capacitance (PVCAP) (T0: 486.19 ± 169.89 ml*mmHg, T1: 540.03 ± 170.59 ml*mmHg; p=0.040). These differences were not observed in the control group (n=16) OUES (T0: 1.62 ± 0.40, T1: 1.77 ± 0.47; p=0.268) and PVCAP (T0: 446.94 ± 144.80 ml*mmHg, T1: 465.81 ± 124.34 ml*mmHg; p=0.590).

Conclusion: Long-term treatment with pyridostigmine improved aerobic capacity in ME/CFS as demonstrated by an increase in OUES, mediated by improvements in central hemodynamics (PVCAP).

Source: Johanna Squires, Sarra Al-Zayer, David Systrom. Exercise capacity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) treated with long-term pyridostigmine. European Respiratory Journal Sep 2023, 62 (suppl 67) PA4639; DOI: 10.1183/13993003.congress-2023.PA4639 https://erj.ersjournals.com/content/62/suppl_67/PA4639

Incidence and persistence of post-COVID condition in children – a matched cohort study in Germany

Abstract:

Introduction: Long-term health effects of COVID-19 have been investigated by several large cohort studies. As most of these studies have been conducted in adults, data on the incidence and persistence of post-COVID-19 condition (PCC) among children and adolescents are still limited.
Methods: Using routine healthcare data from statutory health insurance in Germany, children and adolescents with laboratory-confirmed COVID-19 in 2020 were matched to controls (neither documented nor clinically suspected COVID-19) and followed for incident health conditions until 2021-09-30. To study PCC in children we considered selected health outcomes including malaise/fatigue (R53), dyspnea (R06.0), and cognitive dysfunction (F06.7, U51, R41), developmental delay (F80-89), adjustment disorder (F43), chronic fatigue syndrome (CFS; G93.3), and altered smell/anosmia (R43). The incidence of PCC was determined based on the lack of related diagnoses in the 12 months preceding the index quarter. For each outcome incidence rate ratios (IRR) were estimated using Poisson regression.
Results: At 3-month-follow-up, about 40% more individuals with COVID-19 suffered from at least one of the specified health conditions compared to controls. IRR were highest for smell/anosmia and CFS. IRR were generally higher among adolescents (≥12 years) than among younger children. Only a minority of PCC diagnoses persisted for 12 months within the COVID cohort. Diagnoses were more frequently persistent in the younger age group after one year.
Conclusions: Despite that long-term consequences of COVID-19 are less common and usually less severe in children, a considerable share of those diagnosed with PCC still suffered from specific symptoms 12 months after acute infection. Considering the high number of infected persons our findings suggest a relevant PCC related burden for health care even among children and adolescents.
Key messages:

• In routine healthcare data adolescents showed stronger associations between COVID-19 and post COVID-19 related ICD-10 diagnoses than children < 12 years of age.

• Serious ICD-10 diagnoses persisted for a longer time in younger children than adolescents.

Source: F Ehm, D Wende, F Loser, A Vivirito, S Menzer, M Batram, T Buschmann, G Sarganas, C Scheidt-Nave, J Schmitt, Incidence and persistence of post-COVID condition in children – a matched cohort study in Germany, European Journal of Public Health, Volume 33, Issue Supplement_2, October 2023, ckad160.095, https://doi.org/10.1093/eurpub/ckad160.095 https://academic.oup.com/eurpub/article/33/Supplement_2/ckad160.095/7327923 (Full text available as PDF file)

The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

Abstract:

There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies.

Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity.

Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored.

Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.

Source: Li, J., Zhou, Y., Ma, J. et al. The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID. Sig Transduct Target Ther 8, 416 (2023). https://doi.org/10.1038/s41392-023-01640-z https://www.nature.com/articles/s41392-023-01640-z (Full text)

Long-term Prognosis at 1.5 years after Infection with Wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron Variants

Highlights:

  • Trajectory of long COVID in SARS-CoV-2 wild-type, Alpha, Delta, and Omicron
  • Similar patterns of symptoms and severity of long COVID across all four variants
  • No clinically significant decline in median severity up to 1.5 years after infection
  • More than 50% of long COVID patients failed to improve using any outcome measure
  • Patients infected with Omicron may experience severe non-improving long COVID

Abstract:

Objectives: Knowledge is limited on how changing SARS-CoV-2 variants may translate into different characteristics and affect prognosis of patients with long COVID, especially following Omicron variants. We compared long-term prognosis of patients in a Danish Post COVID Clinic infected with wild-type strain, Alpha, Delta, or Omicron variants as well as the pre-Omicron compared to the Omicron period.

Methods: At enrollment a Post COVID symptom Questionnaire (PCQ), and standard health scores, were registered, and repeated four times until 1.5 years after infection. PCQ was the primary outcome to assess severity of long COVID, and delta PCQ to assess failure to improve.

Results: A total of 806 patients were enrolled. Patients infected with Omicron and Delta variants presented with more severe long COVID (median PCQ 43 in Delta vs 38 in wild-type, P=0.003) and health scores (EQ5D-index was 0.70 in Omicron vs 0.76 in wild-type, P=0.009 and 0.78 pre-Omicron, P=0.006). At 1.5 year after infection patients had no clinically meaningful decline in severity of long COVID, and 57% (245/429) of patients failed to improve 1.5 years after infection, with no differences between variants.

Conclusions: More than half of patients referred to a Post COVID Clinic failed to improve in long COVID severity 1.5 years after infection regardless of variants of SARS-CoV-2.

Source: Jane Agergaard , Jesper Damsgaard Gunst , Berit Schiøttz-Christensen , Lars Østergaard , Christian Wejse , Long-term Prognosis at 1.5 years after Infection with Wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron Variants, International Journal of Infectious Diseases (2023), doi: https://doi.org/10.1016/j.ijid.2023.10.022 https://www.ijidonline.com/article/S1201-9712(23)00760-9/fulltext (Full text)