Tag: prognosis

Development of an expert system for the classification of myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe condition with an uncertain origin and a dismal prognosis. There is presently no precise diagnostic test for ME/CFS, and the diagnosis is determined primarily by the presence of certain symptoms. The current study presents an explainable artificial intelligence (XAI) integrated machine learning (ML) framework that identifies and classifies potential metabolic biomarkers of ME/CFS.

Metabolomic data from blood samples from 19 controls and 32 ME/CFS patients, all female, who were between age and body mass index (BMI) frequency-matched groups, were used to develop the XAI-based model. The dataset contained 832 metabolites, and after feature selection, the model was developed using only 50 metabolites, meaning less medical knowledge is required, thus reducing diagnostic costs and improving prognostic time. The computational method was developed using six different ML algorithms before and after feature selection. The final classification model was explained using the XAI approach, SHAP.

The best-performing classification model (XGBoost) achieved an area under the receiver operating characteristic curve (AUCROC) value of 98.85%. SHAP results showed that decreased levels of alpha-CEHC sulfate, hypoxanthine, and phenylacetylglutamine, as well as increased levels of N-delta-acetylornithine and oleoyl-linoloyl-glycerol (18:1/18:2)[2], increased the risk of ME/CFS. Besides the robustness of the methodology used, the results showed that the combination of ML and XAI could explain the biomarker prediction of ME/CFS and provided a first step toward establishing prognostic models for ME/CFS.

Source: Yagin FH, Shateri A, Nasiri H, Yagin B, Colak C, Alghannam AF. Development of an expert system for the classification of myalgic encephalomyelitis/chronic fatigue syndrome. PeerJ Comput Sci. 2024 Mar 20;10:e1857. doi: 10.7717/peerj-cs.1857. PMID: 38660205; PMCID: PMC11041999. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11041999/ (Full text)

Factors Influencing the Prognosis of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term debilitating multisystem condition with poor prognosis. Studies that examined predictors of ME/CFS outcomes yielded contradictory results. We aimed to explore epidemiological and clinical prognostic factors of ME/CFS using operationalized criteria for recovery/improvement.
Adult ME/CFS patients who attended the Internal Medicine Department of Angers University Hospital, Angers, France between October 2011 and December 2019, and were followed up until December 2020, were included retrospectively. Their medical records were reviewed for data collection. Patients were classified into two groups according to the presence or absence of recovery/improvement (R/I) and compared for epidemiological characteristics, fatigue features, post-exertional malaise severity, clinical manifestations, and comorbidities.
The subgroups of recovered and significantly improved patients were then compared. 168 patients were included. Recovery and improvement rates were 8.3% and 4.8%, respectively. Older age at disease onset was associated with R/I (OR 1.06 [95% CI 1.007–1.110] (p = 0.028)), while diagnostic delay was inversely associated with R/I (OR 0.98 [95% CI 0.964–0.996] (p = 0.036)). The study findings confirmed the poor prognosis of ME/CFS and the deleterious effect of diagnostic delay on disease progression. Interestingly, being older at disease onset was associated with better outcomes, which offers hope to patients for recovery/improvement even at an advanced age.
Source: Ghali A, Lacout C, Fortrat J-O, Depres K, Ghali M, Lavigne C. Factors Influencing the Prognosis of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Diagnostics. 2022; 12(10):2540. https://doi.org/10.3390/diagnostics12102540  https://www.mdpi.com/2075-4418/12/10/2540 (Full text available as PDF file)

Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study

Abstract:

Background: The purpose of this study was to follow-up an Australian cohort of adolescents newly-diagnosed with ME/CFS at a tertiary paediatric ME/CFS clinic and healthy controls over a mean period of two years (range 1-5 years) from diagnosis. Objectives were to (a) examine changes over time in health and psychological wellbeing, (b) track ME/CFS symptomatology and fulfillment of paediatric ME/CFS diagnostic criteria over time, and (c) determine baseline predictors of ME/CFS criteria fulfilment at follow-up.

Methods: 34 participants aged 13-18 years (25 ME/CFS, 23 controls) completed standardised questionnaires at diagnosis (baseline) and follow-up assessing fatigue, sleep quality and hygiene, pain, anxiety, depression, and health-related quality of life. ME/CFS symptomatology and diagnostic criteria fulfilment was also recorded.

Results: ME/CFS patients showed significant improvement in most health and psychological wellbeing domains over time, compared with controls who remained relatively stable. However, fatigue, pain, and health-related quality of life remained significantly poorer amongst ME/CFS patients compared with controls at follow-up. Sixty-five percent of ME/CFS patients at baseline continued to fulfil ME/CFS diagnostic criteria at follow-up, with pain the most frequently experienced symptom. Eighty-two percent of patients at follow-up self-reported that they still had ME/CFS, with 79% of these patients fulfilling criteria. No significant baseline predictors of ME/CFS criteria fulfilment at follow-up were observed, although pain experienced at baseline was significantly associated with criteria fulfilment at follow-up (R = 0.6, p = 0.02).

Conclusions: The majority of Australian adolescents with ME/CFS continue to fulfil diagnostic criteria at follow-up, with fatigue, pain, and health-related quality of life representing domains particularly relevant to perpetuation of ME/CFS symptoms in the early years following diagnosis. This has direct clinical impact for treating clinicians in providing a more realistic prognosis and highlighting the need for intervention with young people with ME/CFS at the initial diagnosis and start of treatment.

Source: Josev EK, Cole RC, Scheinberg A, Rowe K, Lubitz L, Knight SJ. Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study. J Clin Med. 2021 Aug 16;10(16):3603. doi: 10.3390/jcm10163603. PMID: 34441898. https://pubmed.ncbi.nlm.nih.gov/34441898/

Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients

Abstract:

BACKGROUND: Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) is a complex multifactorial disorder of unknown cause having multi-system manifestations. Although the aetiology of CFS/ME remains elusive, immunological dysfunction and more particularly reduced cytotoxic activity in natural killer (NK) cells is the most consistent laboratory finding. The Transient Receptor Potential (TRP) superfamily of cation channels play a pivotal role in the pathophysiology of immune diseases and are therefore potential therapeutic targets. We have previously identified single nucleotide polymorphisms in TRP genes in peripheral NK cells from CFS/ME patients. We have also described biochemical pathway changes and calcium signaling perturbations in NK cells from CFS/ME patients. Notably, we have previously reported a decrease of TRP cation channel subfamily melastatin member 3 (TRPM3) function in NK cells isolated from CFS/ME patients compared with healthy controls after modulation with pregnenolone sulfate and ononetin using a patch-clamp technique. In the present study, we aim to confirm the previous results describing an impaired TRPM3 activity in a new cohort of CFS/ME patients using a whole cell patch-clamp technique after modulation with reversible TRPM3 agonists, pregnenolone sulfate and nifedipine, and an effective TRPM3 antagonist, ononetin. Indeed, no formal research has commented on using pregnenolone sulfate or nifedipine to treat CFS/ME patients while there is evidence that clinicians prescribe calcium channel blockers to improve different symptoms.

METHODS: Whole-cell patch-clamp technique was used to measure TRPM3 activity in isolated NK cells from twelve age- and sex-matched healthy controls and CFS/ME patients, after activation with pregnenolone sulfate and nifedipine and inhibition with ononetin.

RESULTS: We confirmed a significant reduction in amplitude of TRPM3 currents after pregnenolone sulfate stimulation in isolated NK cells from another cohort of CFS/ME patients compared with healthy controls. The pregnenolone sulfate-evoked ionic currents through TRPM3 channels were again significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients. In addition, we used nifedipine, another reversible TRPM3 agonist to support the previous findings and found similar results confirming a significant loss of the TRPM3 channel activity in CFS/ME patients.

CONCLUSIONS: Impaired TRPM3 activity was validated in NK cells isolated from CFS/ME patients using different pharmacological tools and whole-cell patch-clamp technique as the gold standard for ion channel research. This investigation further helps to establish TRPM3 channels as a prognostic marker and/ or a potential therapeutic target for CFS/ME.

Source: Cabanas H, Muraki K, Balinas C, Eaton-Fitch N, Staines D, Marshall-Gradisnik S. Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients. Mol Med. 2019 Apr 23;25(1):14. doi: 10.1186/s10020-019-0083-4. https://www.ncbi.nlm.nih.gov/pubmed/31014226

Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome

Abstract:

Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Interstitial cystitis/painful bladder syndrome (IC/PBS) comprises pain perceived to be from the bladder, urinary urgency and frequency, and nocturia. As diagnosed at present, it is primarily identified in adult women. It is a chronic disease yet its natural history has not been well studied. In a prospective study of 304 incident female IC/PBS cases followed for a median of 33 months after onset, women with baseline chronic fatigue syndrome had a worse prognosis for IC/PBS. Mild IC/PBS at baseline was the only variable that was directly associated with a good prognosis.

OBJECTIVE: To identify baseline variables that predict the prognosis of interstitial cystitis/painful bladder syndrome (IC/PBS) in women seeking medical care for recent onset of this syndrome.

SUBJECTS AND METHODS: In a prospective study of women with incident IC/PBS (≤12 months of symptoms), we contacted patients at intervals and asked standardized questions about IC/PBS symptoms in the previous week. Logistic regression analyses assessed baseline variables as predictors of mild vs more severe IC/PBS at the last follow-up.

RESULTS: Median length of follow-up was 33 months after onset of IC/PBS; 304 (97%) patients had at least one follow-up assessment. Mild IC/PBS at baseline was the only variable that was directly associated with a mild IC/PBS endpoint. Conversely, a history of chronic fatigue syndrome (CFS) was inversely associated with a mild endpoint of IC/PBS (i.e. individuals with CFS had a worse prognosis for their IC/PBS symptoms).

CONCLUSIONS: At a median of nearly 3 years after onset, baseline mild IC/PBS was directly associated with a milder disease severity. Baseline co-morbid CFS was associated with more severe disease. Whether CFS was uniquely associated or represented several co-morbid non-bladder syndromes (NBSs) could not be determined.

© 2012 BJU INTERNATIONAL.

Comment in: Re: prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. [J Urol. 2013]

 

Source: Warren JW, Clauw DJ, Langenberg P. Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. BJU Int. 2013 Mar;111(3 Pt B):E92-7. doi: 10.1111/j.1464-410X.2012.11422.x. Epub 2012 Aug 9. http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2012.11422.x/full (Full article)

Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study

Abstract:

OBJECTIVE: The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds.

METHODS: A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined.

RESULTS: The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue.

CONCLUSIONS: The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.

 

Source: Rimes KA, Goodman R, Hotopf M, Wessely S, Meltzer H, Chalder T. Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study. Pediatrics. 2007 Mar;119(3):e603-9. https://www.ncbi.nlm.nih.gov/pubmed/17332180

 

Prospective study of the prognosis of unexplained chronic fatigue in a clinic-based cohort

Abstract:

OBJECTIVES: To determine prospective changes in clinical status related to chronic fatigue over an 18-month period, and to test demographic and clinical predictors of outcome.

METHODS: A cohort of 100 patients with unexplained chronic fatigue (UCF), which encompasses both chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF), completed questionnaire measures and medical and psychiatric evaluations on four occasions, each six months apart.

RESULTS: Approximately 21% of the sample did not meet criteria for either CFS or ICF at their last research appointment 1.5 years after their index visit. Vitality increased over time, and physical functioning tended to improve, but UCF symptoms did not decrease significantly. Less education, being unemployed, worse mental health, more use of sedating and antidepressant medications, and more somatic attributions for their symptoms were associated with worsening symptom severity over time. Older age, current depression, and more somatic attributions predicted worsening physical functioning. Better mental health, less use of sedating medications, and fewer somatic attributions for illness were significant predictors of increases in vitality.

CONCLUSIONS: Demographic and clinical variables predict outcomes over time among a cohort of patients with unexplained chronic fatigue.

 

Source: Schmaling KB, Fiedelak JI, Katon WJ, Bader JO, Buchwald DS. Prospective study of the prognosis of unexplained chronic fatigue in a clinic-based cohort. Psychosom Med. 2003 Nov-Dec;65(6):1047-54. http://www.ncbi.nlm.nih.gov/pubmed/14645784

 

One-year outcome of unexplained fatigue syndromes in primary care: results from an international study

Abstract:

BACKGROUND: Outcome studies of chronic fatigue, neurasthenia and other unexplained fatigue syndromes are few and have been carried out in developed Western countries. This paper aimed to study the outcome of unexplained fatigue syndromes in an international primary care sample and to identify risk factors for persistence.

METHOD: We used data from the WHO collaborative study of psychological problems in general health care, in which 3201 primary care attenders from 14 countries were followed-up for 12 months. The assessment included a modified version of the Composite International Diagnostic Interview.

RESULTS: Unexplained fatigue persisted in one-fifth to one-third of the subjects depending on the definition of fatigue. From the factors studied only severity of fatigue and psychiatric morbidity at baseline were associated with persistence 12 months later. Outcome did not differ between countries of different stages of economic development.

CONCLUSIONS: The prognosis of fatigue syndromes in international primary care is relatively good. The study underlines the importance of psychological factors in influencing short-term prognosis.

 

Source: Skapinakis P, Lewis G, Mavreas V. One-year outcome of unexplained fatigue syndromes in primary care: results from an international study. Psychol Med. 2003 Jul;33(5):857-66. http://www.ncbi.nlm.nih.gov/pubmed/12877400

 

Prognosis of chronic fatigue in a community-based sample

Abstract:

OBJECTIVE: This study examined predictors of fatigue severity and predictors of continued chronic fatigue status at wave 2 follow-up within a random, community-based sample of individuals previously evaluated in a wave 1 prevalence study of chronic fatigue and chronic fatigue syndrome that originally took place between 1995 and 1997.

METHODS: Wave 1 data were from a larger community-based prevalence study of chronic fatigue syndrome. In the present study, a second wave of data were collected by randomly selecting a sample of participants from the wave 1 sample of 18,675 adults and readministering a telephone screening questionnaire designed to assess symptoms of chronic fatigue syndrome.

RESULTS: Findings revealed that wave 1 fatigue severity was a predictor of fatigue severity at wave 2 in the overall sample of individuals with and without chronic fatigue. In the smaller sample of individuals with chronic fatigue, wave 1 fatigue severity, worsening of fatigue with physical exertion, and feeling worse for 24 hours or more after exercise significantly predicted continued chronic fatigue status (vs. improvement) at wave 2 follow-up.

CONCLUSIONS: These findings underscore the prognostic validity of postexertional malaise in predicting long-term chronic fatigue and also highlight the importance of using population-based, representative random samples when attempting to identify long-term predictors of chronic fatigue at follow-up.

 

Source: Taylor RR, Jason LA, Curie CJ. Prognosis of chronic fatigue in a community-based sample. Psychosom Med. 2002 Mar-Apr;64(2):319-27. http://www.ncbi.nlm.nih.gov/pubmed/11914449

 

The course of severe chronic fatigue syndrome in childhood

Abstract:

Little has been reported on prognostic indicators in children with chronic fatigue syndrome (CFS). We used interviews with children and parents, a mean of 45.5 months after illness onset, to follow up 25 cases of CFS referred to tertiary paediatric psychiatric clinics. At its worst, the illness had been markedly handicapping (prolonged bed-rest and school absence in two-thirds); mean time out of school was one academic year. Two-thirds, however, had recovered and resumed normal activities–mean duration of illness to recovery/assessment 38 months–and none had developed other medical conditions. Recovery was associated with specific physical triggers to the illness, with start of illness in the autumn school term and with higher socioeconomic status. Severe fatigue states in children can cause serious and longlasting handicap but most children recover.

Comment in: Chronic fatigue syndrome in mother and child. [J R Soc Med. 2000]

 

Source: Rangel L, Garralda ME, Levin M, Roberts H. The course of severe chronic fatigue syndrome in childhood. J R Soc Med. 2000 Mar;93(3):129-34. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297949/ (Full article)