Increased Incidence of Fatigue in Patients with Primary Immunodeficiency Disorders: Prevalence and Associations Within the US Immunodeficiency Network Registry

Introduction

Patients with primary immunodeficiency (PID) often report fatigue, yet this symptom has not been studied in PID. Fatigue affects 6–7.5% of healthy adults. The goal of this study is to estimate the prevalence of fatigue in patients with PID and investigate its associated factors.

Methods

We analyzed 2537 PID patients registered in USIDNET to determine responses to the field “fatigue” in the core registry form. Demographics, immune phenotypes, and comorbid conditions were compared between fatigued and non-fatigued patients to identify relevant associations and potential drivers. A focused analysis was performed for patients with predominantly antibody deficiency disorders (PADs).

Results

Fatigue was reported in 25.9% (95% CI 23.7–28.3) of PAD patients, compared to 6.4% (95% CI 4.9–8.2) of non-PAD. Patients with common variable immunodeficiency (CVID) had the highest prevalence of fatigue (p < 0.001) among all PID diagnoses. Other factors that were associated with a higher rate of fatigue among PAD patients included female sex, higher BMI, depression, bronchiectasis, and autoimmunity. Additionally, fatigued PAD patients had lower absolute lymphocyte, CD3, CD4, and CD8 counts compared to non-fatigued patients.

Conclusion

Our findings suggest that fatigue is overrepresented in PAD patients. Prospective studies to estimate prevalence, risk factors, and fatigue etiology in PID are warranted, so therapeutic interventions can be considered.

     

Cross-Cultural Study of Information Processing Biases in Chronic Fatigue Syndrome: Comparison of Dutch and UK Chronic Fatigue Patients

Purpose

This study aims to replicate a UK study, with a Dutch sample to explore whether attention and interpretation biases and general attentional control deficits in chronic fatigue syndrome (CFS) are similar across populations and cultures.

Method

Thirty eight Dutch CFS participants were compared to 52 CFS and 51 healthy participants recruited from the UK. Participants completed self-report measures of symptoms, functioning, and mood, as well as three experimental tasks (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) versus neutral words, (ii) interpretive bias task measuring positive versus somatic interpretations of ambiguous information, and (iii) the Attention Network Test measuring general attentional control.

Results

Compared to controls, Dutch and UK participants with CFS showed a significant attentional bias for illness-related words and were significantly more likely to interpret ambiguous information in a somatic way. These effects were not moderated by attentional control. There were no significant differences between the Dutch and UK CFS groups on attentional bias, interpretation bias, or attentional control scores.

Conclusion

This study replicated the main findings of the UK study, with a Dutch CFS population, indicating that across these two cultures, people with CFS demonstrate biases in how somatic information is attended to and interpreted. These illness-specific biases appear to be unrelated to general attentional control deficits.

     

Perspectives on the ethical concerns and justifications of the 2006 Centers for Disease Control and Prevention HIV testing recommendations

Background

In 2006, the Centers for Disease Control and Prevention (CDC) recommended three changes to HIV testing methods in US healthcare settings: (1) an opt-out approach, (2) removal of separate signed consent, and (3) optional HIV prevention counseling. These recommendations led to a public debate about their moral acceptability.

Methods

We interviewed 25 members from the fields of US HIV advocacy, care, policy, and research about the ethical merits and demerits of the three changes to HIV testing methods. We performed a qualitative analysis of the participant responses in the interviews and summarized the major themes.

Results

In general, arguments in favor of the methods were based upon their ultimate contribution to increasing HIV testing and permitting the consequent benefits of identifying those who are HIV infected and linking them to further care.

Conclusions

The prevailing theme of ethical concern focused on suspicions that the methods might not be properly implemented, and that further safeguards might be needed.

     

Investigating the Effectiveness,Acceptability and Impact on Healthcare Usage of Providing a Cognitive-Behavioural Based Psychological Therapy Service for Patients with Primary Antibody Deficiency

Purpose

Patients with primary antibody deficiency report poorer quality of life and higher rates of anxiety and depression than the general population. Cognitive-behavioral therapy has been shown to be a valuable treatment for patients with other long-term physical health conditions, improving well-being and enabling them to manage their symptoms more effectively. The aim of this project was to establish the feasibility and effectiveness of providing cognitive-behavioral based therapy to patients with primary antibody deficiency.

Methods

Forty-four patients completed a course of psychological therapy. Participants completed a series of self-report measures examining psychological and physical health, and service usage, prior to starting treatment and following their final session. They also provided feedback on their experience of treatment.

Results

Patients showed improvements in anxiety, depression, insomnia and fatigue. There was a high level of acceptability of the service and the potential for long-term cost savings to the NHS.

Conclusion

Psychological therapy based on the cognitive-behavioral model of treatment appears to be a valuable treatment for patients with primary antibody deficiency and comorbid mental health difficulties.

     

Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment

Background

Cytokine disturbances have been suggested to be associated with the Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) for decades.

Methods

Fifty female CFS patients were included in a study on the effect of the interleukin-1-receptor antagonist anakinra or placebo during 4 weeks. EDTA plasma was collected from patients before and directly after treatment. At baseline, plasma samples were collected at the same time from 48 healthy, age-matched female neighborhood controls. A panel of 92 inflammatory markers was determined in parallel in 1 μL samples using a ‘proximity extension assay’ (PEA) based immunoassay. Since Transforming growth factor beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra) were not included in this platform, these cytokines were measured with ELISA.

Results

In CFS/ME patients, the ‘normalized protein expression’ value of IL-12p40 and CSF-1 was significantly higher (p value 0.0042 and 0.049, respectively). Furthermore, using LASSO regression, a combination of 47 markers yielded a prediction model with a corrected AUC of 0.73. After correction for multiple testing, anakinra had no effect on circulating cytokines. TGF-β did not differ between patients and controls.

Conclusions

In conclusion, this study demonstrated increased IL-12p40 and CSF-1 concentrations in CFS/ME patients in addition to a set of predictive biomarkers. There was no effect of anakinra on circulating cytokines other than IL-1Ra. Trial Registration: ClinicalTrials.gov Identifier: NCT02108210, Registered April 2014

     

Physical Behavior Profiles in Chronic Cancer-Related Fatigue

Purpose

Increasing physical activity level is a generally effective intervention goal for patients who suffer from chronic cancer-related fatigue (CCRF). However, patients are unlikely to benefit equally from these interventions, as their behavioral starting points might vary substantially. Therefore, we explored patterns of physical behavior of participants who suffer from CCRF.

Methods

Baseline data of a randomized controlled trial were used for a latent profile analysis on nine accelerometer-derived physical behavior measures, describing levels and patterns of physical activity, moderate-to-vigorous intensity physical activity (MVPA), and sedentary behavior. The relation between participant characteristics and the latent profiles was analyzed.

Results

Accelerometer data of 172 participants from the Netherlands was analyzed. Three latent profiles were distinguished that differed most on physical activity level and total time spent in MVPA. Eighty-eight percent of all participants were assigned to a profile with a probability higher than 8. Age and perceiving limitations by comorbid conditions and pain were significant covariates of profile membership.

Conclusions

We distinguished three physical behavior profiles. The differences between the patterns indicate that the heterogeneity of this sample requires patients to have substantially different treatment goals. Further research should test the applicability of these profiles in clinical practice.

     

Histamine intolerance: a metabolic disease?

Objective

To evaluate the evidence regarding the disease concept of histamine intolerance as a state of inadequate histamine inactivation.

Methods

Keyword-based systematic screening of the scientific literature and of public websites focusing on diagnostic and therapeutic procedures.

Results

Histamine intolerance is commonly diagnosed based solely on subjective reporting of symptoms instead of following systematic diagnostic procedures based on objective laboratory and physical parameters. The only effective long-term therapy is avoidance of histamine-containing food.

Conclusions

The concept of histamine intolerance as a metabolic disease is in need of more experimental and clinical evidence and affected patients will benefit from a clear, evidence-based diagnostic and therapeutic regime.

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Lack of MMP-9 expression is a marker for poor prognosis in Dukes’ B colorectal cancer

Background

Matrix metalloproteinases (MMPs) play a role in cancer progression by degrading extracellular matrix and basement membranes, assisting in tumour neovascularization and in supporting immune response in cancer.

Methods

We studied the prognostic value of immunohistochemical expression of MMP-2, MMP-8, and MMP-9 in a series of 619 colorectal cancer patients using tissue microarray specimens.

Results

Of the samples, 56% were positive for MMP-2, 78% for MMP-8, and 60% for MMP-9. MMP-9 associated with low WHO grade (p?<?0.001). In univariate analysis of Dukes’ B tumours, MMP-9 negativity associated with poor survival (p?=?0.018), and MMP-9 positivity was an independent prognostic marker in multivariate analysis of these tumours (p?=?0.034).

Conclusion

Negative MMP-9 expression can predict poor prognosis in Dukes’ B colorectal tumours and may prove useful for identifying patients, who should be offered adjuvant treatment.

     

Stressful Parental-Bonding Exaggerates the Functional and Emotional Disturbances of Primary Dysmenorrhea

Background

Some evidence suggests that women with primary dysmenorrhea (or painful period) often have traumatic experience with parental attachments, but the exact relationship is still unclear.

Purpose

This study aims to investigate associations between styles of the parental bonding and the detailed aspects of the disorder in Chinese university-student women.

Methods

From university-student women, we have invited 50 primary dysmenorrhea patients and 111 healthy volunteers, to undergo tests of the Functional and Emotional Measure of Dysmenorrhea (FEMD), the Family Relationship Questionnaire (FRQ), and the visual analogue scale for the pain intensity experienced.

Results

Besides the high scores of the FEMD Functional and Emotional scales, the dysmenorrhea patients also scored significantly higher than the healthy controls on the FRQ scales of Paternal Dominance and Maternal Abuse. In patients, the FEMD Emotional scale was negatively predicted by the Paternal Freedom Release scale, and the FEMD Functional scale was positively predicted by the Maternal Dominance scale.

Conclusions

Inappropriate parental bonding or chronic traumatic attachment styles have respective relationships with the functional and emotional disturbances experienced by the primary dysmenorrhea patients.

     

Hematopoietic Stem Cell Transplantation for XIAP Deficiency in Japan

Background

X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare immunodeficiency that is characterized by recurrent hemophagocytic lymphohistiocytosis (HLH) and splenomegaly and sometimes associated with refractory inflammatory bowel disease (IBD). Although hematopoietic stem cell transplantation (HSCT) is the only curative therapy, the outcomes of HSCT for XIAP deficiency remain unsatisfactory compared with those for SLAM-associated protein deficiency and familial HLH.

Aim

To investigate the outcomes and adverse events of HSCT for patients with XIAP deficiency, a national survey was conducted.

Methods

A spreadsheet questionnaire was sent to physicians who had provided HSCT treatment for patients with XIAP deficiency in Japan.

Results

Up to the end of September 2016, 10 patients with XIAP deficiency had undergone HSCT in Japan, 9 of whom (90%) had survived. All surviving patients had received a fludarabine-based reduced intensity conditioning (RIC) regimen. Although 5 patients developed post-HSCT HLH, 4 of them survived after etoposide administration. In addition, the IBD associated with XIAP deficiency improved remarkably after HSCT in all affected cases.

Conclusion

The RIC regimen and HLH control might be important factors for successful HSCT outcomes, with improved IBD, in patients with XIAP deficiency.

     

Subjektive schlafbezogene Parameter bei Patienten mit Autismus-Spektrum-Störung

Background

Sleep disorders are common in children and adolescents with autism spectrum disorder. Little is known, however, about sleep in adult patients.

Objectives

Cross-sectional analysis of subjective sleep-related parameters in patients with autism spectrum disorder and healthy control participants.

Materials and methods

Twenty-nine patients with autism spectrum disorder and 50 healthy control participants were investigated using a questionnaire battery and sleep diaries. All analyses were controlled for depression and anxiety.

Results

Patients with autism spectrum disorder had more severe insomnia symptoms, stronger dysfunctional beliefs and attitudes about sleep, an increased sleep effort, and a higher cognitive arousal compared to the control group. In addition to this, the sleep diary data showed earlier bedtimes in those with autism spectrum disorder.

Conclusions

In patients with autism spectrum disorder, sleep onset and sleep maintenance difficulties seem to be accompanied by cognitive alterations that are typically observed in insomnia patients. In light of this, it appears to be worthwhile to investigate the efficacy of cognitive behavioral treatment for insomnia in this patient group.

     

Micronized palmitoylethanolamide reduces joint pain and glial cell activation

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.

     

Ethical Assessment of Human Embryonic Stem Cell Research According to Turkish Muslim Scholars: First Critical Analysis and Some Reflections

Background

Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.

Objective(s)

To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.

Design

Qualitative study.

Setting

Muslim scholars located in different parts of Turkey.

Methods

Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.

Results

Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.

Conclusion

Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.

     

Multicolor Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases

Purpose

Primary immunodeficiency diseases (PIDDs) are rare inherited diseases that impair the human immune system. We established a multicolor flow cytometric assay to comprehensively evaluate the immune status and immunological characteristics of patients with PIDDs.

Methods

Fifty-nine normal controls and 75 patients with PIDDs, including X-linked severe combined immunodeficiency (X-SCID), X-linked agammaglobulinemia (XLA), X-linked hyper IgM syndrome (X-HIGM), ataxia telangiectasia (AT), Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES), and chronic mucocutaneous candidiasis disease (CMCD), were enrolled in this study. Immunophenotyes were evaluated by multicolor flow cytometry using seven different panels that allowed the detection of major leukocyte populations in peripheral blood.

Results

Multicolor flow cytometry revealed distinct leukocyte populations and immunological features of patients with X-SCID, XLA, X-HIGM, AT, WAS, HIES, and CMCD.

Conclusions

Immunophenotyping by multicolor flow cytometry is useful to evaluate immune status and contributes to the diagnosis and management of patients with PIDDs.

     

Appearance Investment,Quality of Life,and Metabolic Control Among Women with Type 1 Diabetes

Background

Concomitants of Type 1 diabetes management include weight gain and dietary restraint. Body image concerns, particularly among women, are therefore common.

Purpose

The study evaluated associations between the appearance investment component of body image, age, quality of life and self-reported metabolic control were examined, along with the practice of insulin restriction as a weight control strategy.

Method

A questionnaire comprising demographic and diabetes-related information, the Appearance Schemas Inventory, and Diabetes Quality of Life Brief Clinical Inventory was completed by Australian women diagnosed with type 1 diabetes (N?=?177).

Results

Self-evaluative salience was higher among younger participants, those with a lower quality of life, and those with better metabolic control of their diabetes, with the relationships between metabolic control and all of age, quality of life, and self-evaluative salience noted to be non-linear. Among participants who reported restricting insulin for weight control, self-evaluative salience was particularly relevant. Motivational salience was not related to other study variables.

Conclusion

Clinically, the provision of information regarding appearance changes that might arise in order to mitigate later body image difficulties is a potentially beneficial adjunct to standard diabetes management protocols that may lead to more successful disease adjustment.

     

Glücklich als Paar – glücklicher Schlaf?

Background

Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.

Objectives

To identify and discuss connections between relationship and sleep quality.

Methods

Review of the literature in electronic databases.

Results

Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.

Conclusions

Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.

     

Type D Personality and Sleep Quality in Coronary Artery Disease Patients With and Without Obstructive Sleep Apnea: Mediating Effects of Anxiety and Depression

Purpose

The study aimed to examine the association between type D personality trait and sleep quality in coronary artery disease (CAD) patients with and without obstructive sleep apnea (OSA) and to explore the mediating effects of anxiety and depression symptoms.

Method

A cross-sectional study was performed in 879 CAD patients attending cardiac rehabilitation program (mean age 57.8 years; SD?=?9.0; 75% men). Participants underwent full-night polysomnography and were classified in OSA (n?=?349) and no OSA (n?=?530) groups. Patients were evaluated for type D personality, subjective sleep quality (Pittsburgh sleep quality index), and symptoms of anxiety and depression (hospital anxiety and depression scale).

Results

Patients with type D personality reported poorer subjective sleep quality than non-type D patients irrespective of the presence of OSA. Type D and negative affectivity (NA) were associated with worse subjective sleep quality in patients with OSA and without OSA. The mediational analysis revealed that type D and NA were indirectly associated with Pittsburgh sleep quality index through anxiety and depression symptoms in no OSA and OSA patients.

Conclusion

In CAD patients, type D personality and NA are associated with worse subjective sleep quality and this association is mediated by depression and anxiety symptoms irrespective of OSA presence.

     

Advice and care for patients who die by voluntarily stopping eating and drinking is not assisted suicide

Background

A competent patient has the right to refuse foods and fluids even if the patient will die. The exercise of this right, known as voluntarily stopping eating and drinking (VSED), is sometimes proposed as an alternative to physician assisted suicide. However, there is ethical and legal uncertainty about physician involvement in VSED. Are physicians advising of this option, or making patients comfortable while they undertake VSED, assisting suicide? This paper attempts to resolve this ethical and legal uncertainty.

Discussion

The standard approach to resolving this conundrum has been to determine whether VSED itself is suicide. Those who claim that VSED is suicide invariably claim that physician involvement in VSED amounts to assisting suicide. Those who claim that VSED is not suicide claim that physician involvement in VSED does not amount to assisting suicide. We reject this standard approach.

Conclusion

We instead argue that, even if VSED is classified as a kind of suicide, physician involvement in VSED is not a form of assisted suicide. Physician involvement in VSED does not therefore fall within legal provisions that prohibit VSED.