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)

Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a Pavlov reflex of the immune response?

Abstract:

Chronic fatigue syndrome is a protracted illness condition (lasting even years) appearing with strong flu symptoms and systemic defiances by the immune system. Here, by means of statistical mechanics techniques, we study the most widely accepted picture for its genesis, namely a persistent acute mononucleosis infection, and we show how such infection may drive the immune system towards an out-of-equilibrium metastable state displaying chronic activation of both humoral and cellular responses (a state of full inflammation without a direct ’causes-effect’ reason).

By exploiting a bridge with a neural scenario, we mirror killer lymphocytes T(K) and B cells to neurons and helper lymphocytes [Formula: see text] and [Formula: see text] to synapses, hence showing that the immune system may experience the Pavlov conditional reflex phenomenon: if the exposition to a stimulus (Epstein-Barr virus antigens) lasts for too long, strong internal correlations among B,T(K) and T(H) may develop ultimately resulting in a persistent activation even though the stimulus itself is removed. These outcomes are corroborated by several experimental findings.

 

Source: Agliari E, Barra A, Vidal KG, Guerra F. Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome as a Pavlov reflex of the immune response? J Biol Dyn. 2012;6:740-62. doi: 10.1080/17513758.2012.704083. https://www.ncbi.nlm.nih.gov/pubmed/22873615

 

Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial

Abstract:

BACKGROUND: This pilot study (ClinicalTrials.gov ID: NCT01507701) assessed the feasibility and safety of clonidine in adolescent chronic fatigue syndrome (CFS). Specifically, we assessed clonidine dosage in relation to a) plasma concentration levels, b) orthostatic cardiovascular responses, and c) possible adverse effects.

FINDINGS: Five adolescent CFS patients (14-19 years old) received 50 μg clonidine twice per day during 14 days in an open, uncontrolled design. Plasma concentration of clonidine was assayed by standard laboratory methods. Changes in orthostatic cardiovascular responses were assessed by a 20o head-up tilt-test (HUT). Adverse effects were mapped by a questionnaire.After 14 days, C0 median (range) of clonidine was 0.21 (0.18-0.36) μg/L, and Cmax median (range) of clonidine was 0.41 (0.38-0.56) μg/L. Also, supine blood pressures and heart rate were lower during clonidine treatment, and the HUT response was closer to the normal response. No serious adverse effects were registered.

CONCLUSION: Clonidine 50 μg BID seems to be safe enough to proceed from a pilot study to a controlled trial in a select group of adolescents with CFS (ClinicalTrials.gov ID: NCT01040429).

 

Source: Fagermoen E, Sulheim D, Winger A, Andersen AM, Vethe NT, Saul JP, Thaulow E, Wyller VB. Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial. BMC Res Notes. 2012 Aug 7;5:418. doi: 10.1186/1756-0500-5-418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461473/ (Full article)

 

Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost-effectiveness analysis

Abstract:

BACKGROUND: The PACE trial compared the effectiveness of adding adaptive pacing therapy (APT), cognitive behaviour therapy (CBT), or graded exercise therapy (GET), to specialist medical care (SMC) for patients with chronic fatigue syndrome. This paper reports the relative cost-effectiveness of these treatments in terms of quality adjusted life years (QALYs) and improvements in fatigue and physical function.

METHODS: Resource use was measured and costs calculated. Healthcare and societal costs (healthcare plus lost production and unpaid informal care) were combined with QALYs gained, and changes in fatigue and disability; incremental cost-effectiveness ratios (ICERs) were computed.

RESULTS: SMC patients had significantly lower healthcare costs than those receiving APT, CBT and GET. If society is willing to value a QALY at £30,000 there is a 62.7% likelihood that CBT is the most cost-effective therapy, a 26.8% likelihood that GET is most cost effective, 2.6% that APT is most cost-effective and 7.9% that SMC alone is most cost-effective. Compared to SMC alone, the incremental healthcare cost per QALY was £18,374 for CBT, £23,615 for GET and £55,235 for APT. From a societal perspective CBT has a 59.5% likelihood of being the most cost-effective, GET 34.8%, APT 0.2% and SMC alone 5.5%. CBT and GET dominated SMC, while APT had a cost per QALY of £127,047. ICERs using reductions in fatigue and disability as outcomes largely mirrored these findings.

CONCLUSIONS: Comparing the four treatments using a health care perspective, CBT had the greatest probability of being the most cost-effective followed by GET. APT had a lower probability of being the most cost-effective option than SMC alone. The relative cost-effectiveness was even greater from a societal perspective as additional cost savings due to reduced need for informal care were likely.

 

Source: McCrone P, Sharpe M, Chalder T, Knapp M, Johnson AL, Goldsmith KA, White PD. Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost-effectiveness analysis. PLoS One. 2012;7(8):e40808. doi: 10.1371/journal.pone.0040808. Epub 2012 Aug 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411573/ (Full article)

 

Orthostatic tolerance testing in a prospective cohort of adolescents with chronic fatigue syndrome and recovered controls following infectious mononucleosis

Abstract:

Chronic fatigue syndrome (CFS) is a complex condition responsible for marked functional impairment. The authors recently reported that 6 months following acute infectious mononucleosis (IM), 13%, of adolescents met criteria for CFS. The authors’ objective was to assess standing orthostatic tolerance (SOT) in adolescents with CFS and in controls 6 months following IM.

In all, 36 of 39 adolescents diagnosed with CFS 6 months following IM and 43 of 50 recovered controls had SOT testing (SOTT) performed. χ(2) Analysis was performed to study the relationships between SOTT and the diagnosis of CFS. Adolescents diagnosed with CFS and recovered controls did not differ significantly in age, weight, or body mass index. The authors found that 9 of 36 adolescents with CFS (25%) versus 9 of 43 recovered controls (21%) had an abnormal SOTT, which was not a statistically significant difference. Adolescents who meet criteria for CFS 6 months following IM do not have, as a group, more standing orthostatic intolerance than recovered controls.

 

Source: Katz BZ, Stewart JM, Shiraishi Y, Mears CJ, Taylor R. Orthostatic tolerance testing in a prospective cohort of adolescents with chronic fatigue syndrome and recovered controls following infectious mononucleosis. Clin Pediatr (Phila). 2012 Sep;51(9):835-9. doi: 10.1177/0009922812455094. Epub 2012 Jul 31. https://www.ncbi.nlm.nih.gov/pubmed/22850676

 

Depressive symptoms and pragmatic rehabilitation for chronic fatigue syndrome

Abstract:

BACKGROUND: Previous research has suggested that depressed mood may predict outcome and moderate response to treatment in chronic fatigue syndrome, although findings have differed between studies.

AIMS: To examine potential moderators of response to pragmatic rehabilitation v. general practitioner treatment as usual in a recent randomised trial for patients with chronic fatigue syndrome in primary care (IRCTN74156610).

METHOD: Simple regressions, with weighting adjustments to allow for missing data, were calculated. Demographic, medical and psychological variables, and treatment arm, were entered separately and as an interaction term. The outcome variable in each case was change in Chalder Fatigue Scale scores, from baseline to 1-year follow-up, our primary outcome point.

RESULTS: Longer illness durations predicted poorer outcome across the two treatment arms. For patients allocated to pragmatic rehabilitation compared with those allocated to treatment as usual, higher levels of depressive symptoms at baseline were associated with smaller improvements in fatigue (P = 0.022).

CONCLUSIONS: For patients in primary care with higher levels of depressive symptoms, either more intensive or longer pragmatic rehabilitation, or cognitive-behavioural therapy, may be required in order to show a significant improvement in fatigue.

 

Source: Wearden AJ, Dunn G, Dowrick C, Morriss RK. Depressive symptoms and pragmatic rehabilitation for chronic fatigue syndrome. Br J Psychiatry. 2012 Sep;201(3):227-32. doi: 10.1192/bjp.bp.111.107474. Epub 2012 Jul 26. http://bjp.rcpsych.org/content/201/3/227.long (Full article)

 

Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

The objectives of this study are to test the hypothesis that the fatigue and accompanying symptoms of Chronic Myalgic Encephalomyelitis/Fatigue Syndrome are in part due to defects in energy provision at the cellular level, and to understand the pathophysiology of the defects so that effective medical intervention can be implemented.

We performed an audit of 138 patients (ages 18-65) diagnosed with ME/CFS and attending a private practice. The patients and 53 normal, healthy controls had the ATP Profile test carried out on neutrophils from a 3-ml venous blood sample. This test yields 6 numerical factors that describe the availability of ATP and the efficiency of oxidative phosphorylation in mitochondria. Other biomedical measurements, including the concentration of cell-free DNA in plasma, were made. The results of the audit are compared with the controls and a previous cohort of 61 patients. We find that all patients tested have measureable mitochondrial dysfunction which correlates with the severity of the illness.

The patients divide into two main groups differentiated by how cellular metabolism attempts to compensate for the dysfunction. Comparisons with exercise studies suggest that the dysfunction in neutrophils also occurs in other cells. This is confirmed by the cell-free DNA measurements which indicate levels of tissue damage up to 3.5 times the normal reference range. The major immediate causes of the dysfunction are lack of essential substrates and partial blocking of the translocator protein sites in mitochondria. The ATP Profile is a valuable diagnostic tool for the clinical management of ME/CFS.

 

Source: Booth NE, Myhill S, McLaren-Howard J. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med. 2012;5(3):208-20. Epub 2012 Jun 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403556/ (Full article)

 

Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression

Abstract:

BACKGROUND: Depression is an inflammatory disorder while many authors declare myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to be a functional disorder. The aim of the present study is to compare inflammatory and cell-mediated immune (CMI) responses between depression and ME/CFS.

METHODS: We measured two proinflammatory cytokines (PICs) in plasma, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), with enzyme-linked immunosorbent assays, and serum neopterin with a radioimmunoassay in controls, ME/CFS and depressive patients.

RESULTS: Plasma PICs were significantly higher in ME/CFS than in depression and higher in both patient groups than in controls. Increased PIC levels in depression were attributable to the presence of fatigue and physio-somatic symptoms. Serum neopterin did not differ significantly between depression and ME/CFS but was higher in both patient groups than in controls. The significant positive correlations between neopterin and either IL-1 or TNF-α were significantly greater in depression than in ME/CFS.

CONCLUSIONS: Since PICs cause depression-like behaviors and fatigue/malaise, we suggest that inflammation may play a role in the pathophysiology of ME/CFS and depression. Increased neopterin also seems to contribute to the pathophysiology of both disorders. This study has detected a shared ‘pathway phenotype’, i.e. disorders in inflammatory and CMI pathways, which underpins both ME/CFS and depression and, therefore, may explain the co-occurrence of both disorders. ME/CFS and depression are discriminated from each other by increased PICs in ME/CFS and differences in the immune cell communication networks.

Copyright © 2012 S. Karger AG, Basel.

 

Source: Maes M, Twisk FN, Ringel K. Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychother Psychosom. 2012;81(5):286-95. doi: 10.1159/000336803. Epub 2012 Jul 20. https://www.ncbi.nlm.nih.gov/pubmed/22832503

 

Loss of stress response as a consequence of viral infection: implications for disease and therapy

Abstract:

Herein, we propose that viral infection can induce a deficient cell stress response and thereby impairs stress tolerance and makes tissues vulnerable to damage. Having a valid paradigm to address the pathological impacts of viral infections could lead to effective new therapies for diseases that have previously been unresponsive to intervention. Host response to viral infections can also lead to autoimmune diseases like type 1 diabetes. In the case of Newcastle disease virus, the effects of viral infection on heat shock proteins may be leveraged as a therapy for cancer. Finally, the search for a specific virus being responsible for a condition like chronic fatigue syndrome may not be worthwhile if the disease is simply a nonspecific response to viral infection.

 

Source: Hooper PL, Hightower LE, Hooper PL. Loss of stress response as a consequence of viral infection: implications for disease and therapy. Cell Stress Chaperones. 2012 Nov;17(6):647-55. doi: 10.1007/s12192-012-0352-4. Epub 2012 Jul 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468676/ (Full article)

 

Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

According to the World Health Organization, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a neurological disease characterized by widespread inflammation and multi-systemic neuropathology. Aetiology and pathogenesis are unknown, and several agents have been proposed as causative agents or as factors perpetuating the syndrome. Exposure to heavy metals, with particular reference to mercury and gold in dental amalgams, has been considered among the triggers of ME/CFS.

Here we hypothesize that cadmium, a widespread occupational and environmental heavy metal pollutant, might be associated with some of the neurological findings described in ME/CFS. In fact, ME/CFS patients show a decrease of the volume of the gray matter in turn associated with objective reduction of physical activity. Cadmium induces neuronal death in cortical neurons through a combined mechanism of apoptosis and necrosis and it could then be hypothesized that cadmium-induced neuronal cell death is responsible for some of the effects of cadmium on the central nervous system, i.e. a decrease in attention level and memory in exposed humans as well as to a diminished ability for training and learning in rats, that are symptoms typical of ME/CFS. This hypothesis can be tested by measuring cadmium exposure in a cohort of ME/CFS patients compared with matched healthy controls, and by measuring gray matter volume in un-exposed healthy controls, exposed non-ME/CFS subjects, un-exposed ME/CFS patients and exposed ME/CFS patients.

In addition, we hypothesize that cadmium exposure could be associated with reduced cerebral blood flow in ME/CFS patients because of the disruptive effects of cadmium on angiogenesis. In fact, cadmium inhibits angiogenesis and low global cerebral flow is associated with abnormal brain neuroimaging results and brain dysfunction in the form of reduced cognitive testing scores in ME/CFS patients. This hypothesis can be tested by measuring cerebral cortex blood flow in un-exposed healthy controls, exposed non-ME/CFS subjects, un-exposed ME/CFS patients and exposed ME/CFS patients.

If our hypothesis is demonstrated correct, the consequences could affect prevention, early diagnosis, and treatment of ME/CFS. Implications in early diagnosis could entail the evaluation of symptoms typical of ME/CFS in cadmium-exposed subjects as well as the search for signs of exposure to cadmium in subjects diagnosed with ME/CFS. Nutritional supplementation of magnesium and zinc could then be considered, since these elements have been proposed in the prophylaxis and therapy of cadmium exposure, and magnesium was demonstrated effective on ME/CFS patients’ symptom profiles.

Copyright © 2012 Elsevier Ltd. All rights reserved.

 

Source: Pacini S, Fiore MG, Magherini S, Morucci G, Branca JJ, Gulisano M, Ruggiero M. Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Med Hypotheses. 2012 Sep;79(3):403-7. doi: 10.1016/j.mehy.2012.06.007. Epub 2012 Jul 12. https://www.ncbi.nlm.nih.gov/pubmed/22795611