Fatigue in children and adolescents perinatally infected with human immunodeficiency virus: an observational study.

BACKGROUND: Fatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL. METHODS: We measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, and 3) the general Dutch population. Within the PHIV+ group we explored associations between fatigue and HRQOL. RESULTS: We enrolled 14 PHIV+ (median age 10.2 years [IQR 9.2-11.4]) and 14 HIV-. Compared to CCD, PHIV+ significantly reported less general fatigue (mean difference 13.0, 95% CI 1.3 to 24.8). PHIV+ did not score significantly different on any of the other PedsQL MFS scales compared to HIV-, CCD or the general Dutch population. PHIV children scored relatively low on the cognitive fatigue scale in comparison to HIV-uninfected matched controls, CCD and the general population, although these differences did not reach significance. Among PHIV+, a lower score on total fatigue, general fatigue and cognitive fatigue was associated with a lower HRQOL score. CONCLUSIONS: The results of this study suggest that PHIV children and adolescents do not experience more symptoms of fatigue than their healthy peers. However, PHIV children and adolescents may be more likely to experience cognitive fatigue. Fatigue in PHIV also appears to be associated with children's HRQOL. Further research should confirm these exploratory findings.

Reducing fatigue in pediatric rheumatic conditions: a systematic review.

BACKGROUND: Although fatigue is a prevalent distressing symptom in children and adolescents with Pediatric Rheumatic Conditions (PRCs), intervention studies designed for reducing fatigue in PRCs are limited. AIM: To systematically review evidence regarding the efficacy of interventions intended to reduce fatigue in patients with PRCs. METHODS: Comprehensive electronic searches were performed in PubMed/ MEDLINE, Embase, Web of Science and Cinahl. The risk of bias was assessed using the 'Revised Cochrane risk-of-bias tool for randomized trials' and 'Quality Assessment Tool for Before-After Studies With No Control Group' for respectively studies with and without a control group. RESULTS: Ten out of 418 studies were included with a total of 240 participants (age range 5-23 years). Interventions included land-based and aquatic-based exercise therapy, prednisolone, vitamin-D and creatine supplementation, psychological therapy and a transition program into an adult rheumatology program. Fatigue was assessed with self-reported questionnaires in all included studies. Land-based exercise therapy was effective in one pre-post intervention study, whereas not effective in two randomized controlled trials. Aquatic-based exercise therapy was found more effective than land-based exercise therapy. Two placebo-controlled studies showed a significant positive effect in reducing subjective fatigue with prednisolone and vitamin-D. Creatine was not found effective. Cognitive therapy was effective in one pre-post intervention study, while one RCT did not show an effect in reducing fatigue. A transition program based on health education showed a small reducing effect, however, it was not clear if this was a significant effect. Six studies showed a high risk of bias, three studies a moderate risk, and one study had a low risk of bias. CONCLUSIONS: Insufficient evidence is provided to substantiate the efficacy of current interventions to reduce fatigue in PRCs. The low number of studies, non-comparable interventions, risk of bias, and inconclusive outcomes of the included studies denote future research should focus on intervention studies aimed at the treatment of fatigue in children and adolescents with PRCs. Identification of possible underlying biological and psychosocial mechanisms as possible treatment targets to reduce complaints of fatigue in children and adolescents with PRCs is warranted.

No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls.

INTRODUCTION: In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination (2vHPV). After an update of this overview in 2015, concerns regarding the safety of 2vHPV was picked up by the media, which led to further reports of long-lasting fatigue. Therefore, the Dutch National Institute for Public Health and the Environment (RIVM) investigated a possible association between HPV-vaccination and long-term fatigue. METHODS: In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3-6 months in all girls born in 1991-2000 during the follow-up period January 1st 2007-December 31st 2014 (2007-2008 pre-vaccination and 2009-2014 post-vaccination). Patients with certain fatigue ≥6 m were asked for consent to link their primary care information with vaccination data. Incidence rates per 10,000 person years (PY) for 12-16-year-old girls were compared between pre- and post-HPV-vaccine era. A self-controlled case series (SCCS) analysis was performed using consenting vaccinated cases. A primary high-risk period of 12 months after each dose was defined. RESULTS: The cohort consisted of 69,429 12-16-year-old girls accounting for 2758 PY pre-vaccination and 57,214 PY post-vaccination. Differences between pre- and post-vaccination incidences (CFS: 3.6 (95% CI 0.5-25.7)/10,000 PY and 0.9 (0.4-2.1); certain fatigue ≥6 m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6 m: 0.0 and 16.6 (13.6-20.3), respectively) were not statistically significant. SCCS analyses in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI 0.07-5.49). CONCLUSIONS: Fatigue ≥6 m and 3-6 m was frequently found among adolescent girls, but CFS was rarely diagnosed. No statistically significant increased incidence rates were found post-vaccination compared to similar age groups of girls pre-vaccination. The SCCS analysis included a low number of cases but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period.

Pharmacologic interventions for fatigue in cancer and transplantation: a meta-analysis.

Background: Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (hsct). Methods: For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, cinahl, and Psychinfo for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of hsct. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models. Results: In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins (n = 31), stimulants (n = 19), l-carnitine (n = 6), corticosteroids (n = 5), antidepressants (n = 5), appetite stimulants (n = 3), and other agents (n = 48). Fatigue was significantly reduced with erythropoietin [standardized mean difference (smd): -0.52; 95% confidence interval (ci): -0.89 to -0.14] and with methylphenidate (smd: -0.36; 95% ci: -0.56 to -0.15); modafinil (or armodafinil) and corticosteroids were not effective. Conclusions: Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of hsct. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.

[Congenital Intermittent Third-degree Atrioventricular Block Associated with Retinoid Exposure in Pregnancy]. / Konnataler intermittierender AV-Block III° nach Retinoideinnahme in der Schwangerschaft.

BACKGROUND: The retinoid acitretin, which has been approved as an effective therapy for severe keratinization disorders, is highly teratogenic, and exposure in the first trimester of pregnancy is associated with the risk of miscarriage and various malformations, including congenital heart defects. Cardiac conduction system disorders have not been described so far. CASE REPORT: A 24-year-old woman was treated with acitretin for dyskeratosis follicularis until pregnancy was diagnosed at 12 weeks of gestation. The female infant was born after 35 weeks gestation by cesarean section because of intermittent fetal bradycardia. The baby was vigorous at birth (Apgar 9, 10, 10 at 1, 5 and 10 min) but displayed intermittent third-degree atrioventricular block. A search for maternal autoantibodies and viral infections gave negative findings. CONCLUSION: The spectrum of disorders caused by intrauterine retinoid exposure appears to include atrioventricular conduction failure.