The Case Definition of Chronic Fatigue Syndrome

The 1994 case definition of chronic fatigue syndrome is widely used not only for diagnosis but also for clinical and laboratory-based observations of this clinical entity. The criteria for the 1994 case definition are based primarily on symptoms and not on physical signs or chemical or immunological tests. This situation has resulted in conflicting clinical and laboratory observations that in all likelihood is due to different populations of patients being studied in different centers. Based on some of the recent publications, there appears to be an emerging picture of this disease entity that we propose could be used to subgroup chronic fatigue syndrome into four different subclasses. These subclasses would consist of chronic fatigue with primarily nervous system disorders such as impaired memory or concentration and headache, chronic fatigue with primarily endocrine system disorders such as unrefreshing sleep and postexertional malaise, chronic fatigue with musculoskeletal system disorders such as muscle pain and joint pain, and chronic fatigue with immune system/infectious disorders such as sore throat and tender lymph nodes. It is suggested that if clinical and laboratory-based studies on chronic fatigue syndrome were conducted on more homogeneous subgroups of patients, the data from one center to the other might not be as conflicting and more insights can be shed on the nature of this clinical condition.     

Acute Phase Responses and Cytokine Secretion in Chronic Fatigue Syndrome

This study addresses the hypothesis that clinical manifestations of chronic fatigue syndrome (CFS) are due in part to abnormal production of or sensitivity to cytokines such as interleukin-1 (IL-1) and IL-6 under basal conditions or in response to a particular physical stress: 15 min of exercise consisting of stepping up and down on a platform adjusted to the height of the patella. The study involved 10 CFS patients and 11 age-, sex-, and activity-matched controls: of these, 6 patients and 4 controls were tested in both the follicular and the luteal phases of the menstrual cycle, and the remainder were tested in only one phase, for a total of 31 experimental sessions. Prior to exercise, plasma concentrations of the acute phase reactant ₂-macroglobulin were 29% higher in CFS patients (P < 0.008) compared to controls. Secretion of IL-6 was generally higher for CFS patients (~38%), however, this difference was statistically significant only if all values over a 3-day period were analyzed by repeated-measures ANOVA (P = 0.035). IL-6 secretion correlated with plasma ₂-macroglobulin in control subjects at rest (R = 0.767, P = 0.001). Immediately after exercise, the CFS patients reported greater ratings of perceived exertion (P=0.027) compared to the healthy control subjects. Ratings of perceived exertion correlated with IL-1 secretion by cells from healthy control subjects (R = 0.603, P = 0.022), but not from CFS patients, and IL-1 secretion was not different between groups. Exercise induced a slight (<12%) but significant (P = 0.006) increase in IL-6 secretion, but the responses of the CFS patients were not different than controls. Furthermore, no significant exercise-induced changes in body temperature or plasma ₂-macroglobulin were observed. These data indicate that under basal conditions, CFS is associated with increased IL-6 secretion which is manifested by chronically elevated plasma ₂-macroglobulin concentrations. These modest differences suggest that cytokine dysregulation is not a singular or dominant factor in the pathogenesis of CFS.     

Impact of mHealth Chronic Disease Management on Treatment Adherence and Patient Outcomes: A Systematic Review

Background

Adherence to chronic disease management is critical to achieving improved health outcomes, quality of life, and cost-effective health care. As the burden of chronic diseases continues to grow globally, so does the impact of non-adherence. Mobile technologies are increasingly being used in health care and public health practice (mHealth) for patient communication, monitoring, and education, and to facilitate adherence to chronic diseases management.

Objective

We conducted a systematic review of the literature to evaluate the effectiveness of mHealth in supporting the adherence of patients to chronic diseases management (“mAdherence”), and the usability, feasibility, and acceptability of mAdherence tools and platforms in chronic disease management among patients and health care providers.

Methods

We searched PubMed, Embase, and EBSCO databases for studies that assessed the role of mAdherence in chronic disease management of diabetes mellitus, cardiovascular disease, and chronic lung diseases from 1980 through May 2014. Outcomes of interest included effect of mHealth on patient adherence to chronic diseases management, disease-specific clinical outcomes after intervention, and the usability, feasibility, and acceptability of mAdherence tools and platforms in chronic disease management among target end-users.

Results

In all, 107 articles met all inclusion criteria. Short message service was the most commonly used mAdherence tool in 40.2% (43/107) of studies. Usability, feasibility, and acceptability or patient preferences for mAdherence interventions were assessed in 57.9% (62/107) of studies and found to be generally high. A total of 27 studies employed randomized controlled trial (RCT) methods to assess impact on adherence behaviors, and significant improvements were observed in 15 of those studies (56%). Of the 41 RCTs that measured effects on disease-specific clinical outcomes, significant improvements between groups were reported in 16 studies (39%).

Conclusions

There is potential for mHealth tools to better facilitate adherence to chronic disease management, but the evidence supporting its current effectiveness is mixed. Further research should focus on understanding and improving how mHealth tools can overcome specific barriers to adherence.     

Hormonal Influences on Stress-Induced Neutrophil Mobilization in Health and Chronic Fatigue Syndrome

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase. Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion. For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls. In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively). These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.     

Cognitive Behavioral Therapy and Graded Exercise for Chronic Fatigue Syndrome: A Meta‐Analysis

[Clin Psychol Sci Prac 18: 311–324, 2011] Several reviews have concluded that graded exercise therapy (GET) and cognitive behavioral therapy (CBT) may be the most efficacious treatments for chronic fatigue syndrome (CFS). The current review extends the evidence for overall and outcome‐specific effects of CBT and GET by directly comparing the treatments and addressing the methodological limitations of previous reviews. GET (n = 5) and CBT (n = 16) randomized controlled trials were meta‐analyzed. Overall effect sizes suggested that GET (g = 0.28) and CBT (g = 0.33) were equally efficacious. However, CBT effect sizes were lower in primary care settings and for treatments offering fewer hours of contact. The results suggested that both CBT and GET are promising treatments for CFS, although CBT may be a more effective treatment when patients have comorbid anxiety and depressive symptoms.     

Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome,Fibromyalgia, Chronic Fatigue Syndrome,Silicone Breast Implant–Related Symptoms and Post-COVID Syndrome

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant–related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them. The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned. Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant–related symptoms, and post-COVID syndrome, namely “autoimmune autonomic dysfunction syndromes”. Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.     

Sleep Quality and Psychological Adjustment in Chronic Fatigue Syndrome

Without specific etiology or effective treatment, chronic fatigue syndrome (CFS) remains a contentious diagnosis. Individuals with CFS complain of fatigue and poor sleep—symptoms that are often attributed to psychological disturbance. To assess the nature and prevalence of sleep disturbance in CFS and to investigate the widely presumed presence of psychological maladjustment we examined sleep quality, sleep disorders, physical health, daytime sleepiness, fatigue, and psychological adjustment in three samples: individuals with CFS; a healthy control group; and individuals with a definite medical diagnosis: narcolepsy. Outcome measures included physiological evaluation (polysomnography), medical diagnosis, structured interview, and self-report measures. Results indicate that the CFS sample had a very high incidence (58%) of previously undiagnosed primary sleep disorder such as sleep apnea/hypopnea syndrome and restless legs/periodic limb movement disorder. They also had very high rates of self-reported insomnia and nonrestorative sleep. Narcolepsy and CFS participants were very similar on psychological adjustment: both these groups had more psychological maladjustment than did control group participants. Our data suggest that primary sleep disorders in individuals with CFS are underdiagnosed in primary care settings and that the psychological disturbances seen in CFS may well be the result of living with a chronic illness that is poorly recognized or understood.     

Immunological Response in Chronic Fatigue Syndrome Following a Graded Exercise Test to Exhaustion

This study was conducted to evaluate the immunological response to an exhaustive treadmill exercise test in 20 female chronic fatigue syndrome patients compared to 14 matched sedentary controls. Venipuncture was performed at baseline and 4 min, 1 hr, and 24 hr postexercise. White blood cells were labeled for monoclonal antibody combinations and were quantified by FACsan. Cytokines were assayed utilizing quantitative RT/PCR. No group difference was seen in (28.6 ± 1.6 vs 30.9 ± 1.2 ml · kg^–1 · min^–1; P > 0.05). However, 24 hr after exercise the patients' fatigue levels were significantly increased (P < 0.05). The counts of WBC, CD3⁺CD8⁺ cells, CD3⁺CD4⁺ cells, T cells, B cells, natural killer cells, and IFN- changed across time (P's < 0.01). No group differences were seen for any of the immune variables at baseline or after exercise (P's > 0.05). The immune response of chronic fatigue syndrome patients to exhaustive exercise is not significantly different from that of healthy nonphysically active controls.     

Patient and Provider Attitudes Toward the Use of Patient Portals for the Management of Chronic Disease: A Systematic Review

Background

Patient portals provide patients with the tools to better manage and understand their health status. However, widespread adoption of patient portals faces resistance from patients and providers for a number of reasons, and there is limited evidence evaluating the characteristics of patient portals that received positive remarks from patients and providers.

Objective

The objectives of this systematic review are to identify the shared characteristics of portals that receive favorable responses from patients and providers and to identify the elements that patients and providers believe need improvement.

Methods

The authors conducted a systematic search of the CINAHL and PubMed databases to gather data about the use of patient portals in the management of chronic disease. Two reviewers analyzed the articles collected in the search process in order remove irrelevant articles. The authors selected 27 articles to use in the literature review.

Results

Results of this systematic review conclude that patient portals show significant improvements in patient self-management of chronic disease and improve the quality of care provided by providers. The most prevalent positive attribute was patient-provider communication, which appeared in 10 of 27 articles (37%). This was noted by both patients and providers. The most prevalent negative perceptions are security (concerns) and user-friendliness, both of which occurred in 11 of 27 articles (41%). The user-friendliness quality was a concern for patients and providers who are not familiar with advanced technology and therefore find it difficult to navigate the patient portal. The high cost of installation and maintenance of a portal system, not surprisingly, deters some providers from implementing such technology into their practice, but this was only mentioned in 3 of the 27 articles (11%). It is possible that the incentives for meaningful use assuage the barrier of cost.

Conclusions

This systematic review revealed mixed attitudes from patients and their providers regarding the use of patient portals to manage their chronic disease. The authors suggest that a standard patient portal design providing patients with the resources to understand and manage their chronic conditions will promote the adoption of patient portals in health care organizations.     

Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS

The present study examines serum zinc concentrations in patients with chronic fatigue syndrome (CFS) versus normal volunteers. Serum zinc levels were determined by means of an atomic absorption method. We found that serum zinc was significantly lower in the CFS patients than in the normal controls. There was a trend toward a significant negative correlation between serum zinc and the severity of CFS and there was a significant and negative correlation between serum zinc and the subjective experience of infection. We found that serum zinc was significantly and negatively correlated to the increase in the alpha2 protein fraction and positively correlated to decreases in the expression of mitogen-induced CD69+ (a T cell activation marker) on CD3+ as well as CD3+CD8+ T cells. These results show that CFS is accompanied by a low serum zinc status and that the latter is related to signs of inflammation and defects in early T cell activation pathways. Since zinc is a strong anti-oxidant, the present results further support the findings that CFS is accompanied by increased oxidative stress. The results of these reports suggest that some patients with CFS should be treated with specific antioxidants, including zinc supplements.     

The Effects on Health Behavior and Health Outcomes of Internet-Based Asynchronous Communication Between Health Providers and Patients With a Chronic Condition: A Systematic Review

Background

In support of professional practice, asynchronous communication between the patient and the provider is implemented separately or in combination with Internet-based self-management interventions. This interaction occurs primarily through electronic messaging or discussion boards. There is little evidence as to whether it is a useful tool for chronically ill patients to support their self-management and increase the effectiveness of interventions.

Objective

The aim of our study was to review the use and usability of patient-provider asynchronous communication for chronically ill patients and the effects of such communication on health behavior, health outcomes, and patient satisfaction.

Methods

A literature search was performed using PubMed and Embase. The quality of the articles was appraised according to the National Institute for Health and Clinical Excellence (NICE) criteria. The use and usability of the asynchronous communication was analyzed by examining the frequency of use and the number of users of the interventions with asynchronous communication, as well as of separate electronic messaging. The effectiveness of asynchronous communication was analyzed by examining effects on health behavior, health outcomes, and patient satisfaction.

Results

Patients’ knowledge concerning their chronic condition increased and they seemed to appreciate being able to communicate asynchronously with their providers. They not only had specific questions but also wanted to communicate about feeling ill. A decrease in visits to the physician was shown in two studies (P=.07, P=.07). Increases in self-management/self-efficacy for patients with back pain, dyspnea, and heart failure were found. Positive health outcomes were shown in 12 studies, where the clinical outcomes for diabetic patients (HbA1c level) and for asthmatic patients (forced expiratory volume [FEV]) improved. Physical symptoms improved in five studies. Five studies generated a variety of positive psychosocial outcomes.

Conclusions

The effect of asynchronous communication is not shown unequivocally in these studies. Patients seem to be interested in using email. Patients are willing to participate and are taking the initiative to discuss health issues with their providers. Additional testing of the effects of asynchronous communication on self-management in chronically ill patients is needed.     

Fatigue in Cancer: A Review of Literature

Fatigue is a common symptom of advanced cancer limiting one''s activity and affecting the quality of life. It is a multidimensional symptom complex with subjective and objective components. Hence, its definition and assessment seems arbitrary, incomplete, and elusive. Components of fatigue often merge with other ‘disease states’ as anemia, depression and so on, compounding difficulty to assess it separately. Fatigue has a high prevalence rate, and lasts longer in chronic diseases like cancer. Its association with treatment modalities like chemotherapy, radiotherapy alongside the primary disease process makes it seemingly ubiquitous in many cases. Systemic manifestation of cancer causes excess demand on body resources on cell repair, uncontrolled growth with metabolite accumulation causing fatigue. Co-morbid conditions of organic and psychological nature causes fatigue. There are many assessment tools for fatigue with different uses and objectives, simple and reproducible tools like Brief Fatigue Inventory, Edmonton Symptom assessment scale seem feasible in everyday practice. Management of fatigue is not straightforward and rewarding. Although treatment of cause appears to be an attractive option, it is not possible in all cases. Therapeutic agents targeting cytokine load is in early stages of study and available results are not favorable. Specific measures aimed at pain relief, prevention/treatment of sepsis, management of depression, avoidance of drugs causing fatigue, restoring the metabolic profile are important. Methyl phenidate, megestrol, and modafinil are some drugs with promising effect to treat fatigue, though confirmatory studies are yet to be established. Non-pharmacological methods are also helpful. Forewarning patients on upcoming fatigue, active regular exercise, and stress management are some of them. Fatigue being a multidimensional entity, single mode of therapy is insufficient. Combined modality tailored to individual patient need and understanding may be the right way to battle this ill-understood symptom. This review article examines the etiopathogenesis and management strategies of fatigue in cancer.     

Cheiro-Oral Syndrome: A Clinical Analysis and Review of Literature

Purpose

After a century, cheiro-oral syndrome (COS) was harangued and emphasized for its localizing value and benign course in recent two decades. However, an expanding body of case series challenged when COS may arise from an involvement of ascending sensory pathways between cortex and pons and terminate into poor outcome occasionally.

Materials and Methods

To analyze the location, underlying etiologies and prognosis in 76 patients presented with COS collected between 1989 and 2007.

Results

Four types of COS were categorized, namely unilateral (71.1%), typically bilateral (14.5%), atypically bilateral (7.9%) and crossed COS (6.5%). The most common site of COS occurrence was at pons (27.6%), following by thalamus (21.1%) and cortex (15.8%). Stroke with small infarctions or hemorrhage was the leading cause. Paroxysmal paresthesia was predicted for cortical involvement and bilateral paresthesia for pontine involvement, whereas crossed paresthesia for medullary involvement. However, the majority of lesions cannot be localized by clinical symptoms alone, and were demonstrated only by neuroimaging. Deterioration was ensued in 12% of patients, whose lesions were large cortical infarction, medullary infarction, and bilateral subdural hemorrhage.

Conclusion

COS arises from varied sites between medulla and cortex, and is usually caused by small stroke lesion. Neurological deterioration occurs in 12% of patients and relates to large vessel occlusion, medullary involvement or cortical stroke. Since the location and deterioration of COS cannot be predicted by clinical symptoms alone, COS should be considered an emergent condition for aggressive investigation until fatal cause is substantially excluded.     

慢性疲劳综合征患者外周血淋巴细胞亚群及CD25^＋调节性T细胞表达的研究

研究慢性疲劳综合征（CFS）患者外周血淋巴细胞亚群及CD25＋调节性T细胞的表达情况。使用流式细胞仪检测84例CFS患者（CFS组）、50例健康体检者（健康对照组）外周血淋巴细胞亚群（T细胞、CD4＋T细胞、CD8＋T细胞、B细胞、NK细胞）及CD25＋调节性T细胞的表达情况。结果显示,CFS组与健康对照组的T细胞、CD8＋T细胞百分率以及CD4＋/CD8＋比值无显著差别（P〉0.05）;而CFS组NK细胞、CD4＋T细胞及CD25＋调节性T细胞百分率显著增高,B细胞百分率显著降低（P〈0.05）。结论：慢性疲劳综合征患者外周血淋巴细胞各亚群比例异常,提示其免疫功能失衡,而CD25＋T调节性细胞可能在该病进程中有重要意义。     

The Effect of Patient Portals on Quality Outcomes and Its Implications to Meaningful Use: A Systematic Review

Background

The Health Information Technology for Economic and Clinical Health (HITECH) Act imposes pressure on health care organizations to qualify for “Meaningful Use”. It is assumed that portals should increase patient participation in medical decisions, but whether or not the use of portals improves outcomes remains to be seen.

Objective

The purpose of this systemic review is to outline and summarize study results on the effect of patient portals on quality, or chronic-condition outcomes as defined by the Agency for Healthcare Research and Quality, and its implications to Meaningful Use since the beginning of 2011. This review updates and builds on the work by Ammenwerth, Schnell-Inderst, and Hoerbst.

Methods

We performed a systematic literature search in PubMed, CINAHL, and Google Scholar. We identified any data-driven study, quantitative or qualitative, that examined a relationship between patient portals, or patient portal features, and outcomes. We also wanted to relate the findings back to Meaningful Use criteria. Over 4000 articles were screened, and 27 were analyzed and summarized for this systematic review.

Results

We identified 26 studies and 1 review, and we summarized their findings and applicability to our research question. Very few studies associated use of the patient portal, or its features, to improved outcomes; 37% (10/27) of papers reported improvements in medication adherence, disease awareness, self-management of disease, a decrease of office visits, an increase in preventative medicine, and an increase in extended office visits, at the patient’s request for additional information. The results also show an increase in quality in terms of patient satisfaction and customer retention, but there are weak results on medical outcomes.

Conclusions

The results of this review demonstrate that more health care organizations today offer features of a patient portal than in the review published in 2011. Articles reviewed rarely analyzed a full patient portal but instead analyzed features of a portal such as secure messaging, as well as disease management and monitoring. The ability of patients to be able to view their health information electronically meets the intent of Meaningful Use, Stage 2 requirements, but the ability to transmit to a third party was not found in the review.     

eHealth Interventions for HIV Prevention in High-Risk Men Who Have Sex With Men: A Systematic Review

Background

While the human immunodeficiency virus (HIV) incidence rate has remained steady in most groups, the overall incidence of HIV among men who have sex with men (MSM) has been steadily increasing in the United States. eHealth is a platform for health behavior change interventions and provides new opportunities for the delivery of HIV prevention messages.

Objective

The purpose of this systematic review was to examine the use of eHealth interventions for HIV prevention in high-risk MSM.

Methods

We systematically searched PubMed, OVID, ISI Web of Knowledge, Google Scholar, and Google for articles and grey literature reporting the original results of any studies related to HIV prevention in MSM and developed a standard data collection form to extract information on study characteristics and outcome data.

Results

In total, 13 articles met the inclusion criteria, of which five articles targeted HIV testing behaviors and eight focused on decreasing HIV risk behaviors. Interventions included Web-based education modules, text messaging (SMS, short message service), chat rooms, and social networking. The methodological quality of articles ranged from 49.4-94.6%. Wide variation in the interventions meant synthesis of the results using meta-analysis would not be appropriate.

Conclusions

This review shows evidence that eHealth for HIV prevention in high-risk MSM has the potential to be effective in the short term for reducing HIV risk behaviors and increasing testing rates. Given that many of these studies were short term and had other limitations, but showed strong preliminary evidence of improving outcomes, additional work needs to rigorously assess the use of eHealth strategies for HIV prevention in high-risk MSM.