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Journal of Clinical Sleep Medicine :... Sep 2021This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence.
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations.
RESULTS
The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.
CITATION
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. 2021;17(9):1895-1945.
Topics: Adult; Child; Disorders of Excessive Somnolence; GRADE Approach; Humans; Modafinil; Sleep; Sodium Oxybate; United States
PubMed: 34743790
DOI: 10.5664/jcsm.9326 -
Journal of Affective Disorders May 2019To gain insight into the prevalence of apathy, depression and anxiety symptoms in myotonic dystrophy type 1 (DM1) patients on the basis of a systematic review with a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To gain insight into the prevalence of apathy, depression and anxiety symptoms in myotonic dystrophy type 1 (DM1) patients on the basis of a systematic review with a meta-analysis.
METHODS
One author systematically searched and selected studies from Embase, Medline, PsychInfo and Web of Science (index periods up to August 2018). Data extraction and bias assessment were performed independently by two authors. We calculated (1) a weighted pooled prevalence and (2) weighted pooled standardized mean difference (Hedges' g) from studies comparing DM1 patients to healthy and/or neuromuscular disease controls separately for symptoms of depression, anxiety and apathy.
RESULTS
The pooled prevalences of depression (26 studies, n = 1267 DM1 patients), anxiety (19 studies, n = 896) and apathy (5 studies, n = 428), were 18% (95%CI: 12-25), 16 (95%CI: 13-18) and 55% (95%CI: 50-60), respectively. Effect sizes (Hedges' g) for depression, anxiety and apathy in DM1 patients compared to healthy controls were 1.04 (95%-CI: 0.71 to 1.37), 0.87 (95%-CI: 0.51 to 1.24) and 1.13 (95%-CI:0.54-1.71). Effect sizes for symptoms of depression, anxiety and apathy were 0.29 (95% CI: -0.12 to 0.70), 0.45 (95%-CI: -0.31 to 1.22) and 1.12 (95%-CI: 0.32-1.93) for DM1 patients versus neuromuscular disease controls. In most analyses, statistical heterogeneity was high.
CONCLUSIONS
Estimated pooled prevalences of clinically significant levels of symptoms of depression, anxiety and apathy in DM1 are 19, 17 and 55% respectively. Symptoms of depression and anxiety in DM1 may reflect reactive adjustment to progressive impairment and restricted participation similar to other chronic neuromuscular disease. The literature on the prevalence and severity of apathy, although a clinically relevant and characteristic symptom of DM1, is relatively scarce.
Topics: Affective Symptoms; Anxiety Disorders; Apathy; Depressive Disorder; Humans; Myotonic Dystrophy; Prevalence
PubMed: 30870776
DOI: 10.1016/j.jad.2019.03.036 -
Neurology Aug 2017To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1). (Review)
Review
OBJECTIVE
To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1).
METHODS
We searched Embase (index period 1974-2016) and MEDLINE (index period 1946-2016) for studies in patients with DM1 using MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes, clinical-genetic correlations, and information on potential risk of bias. Results were summarized and pooled prevalence of imaging abnormalities was calculated, where possible.
RESULTS
In DM1, various imaging changes are widely dispersed throughout the brain, with apparently little anatomical specificity. We found general atrophy and widespread gray matter volume reductions in all 4 cortical lobes, the basal ganglia, and cerebellum. The pooled prevalence of white matter hyperintensities is 70% (95% CI 64-77), compared with 6% (95% CI 3-12) in unaffected controls. DTI shows increased mean diffusivity in all 4 lobes and reduced fractional anisotropy in virtually all major association, projection, and commissural white matter tracts. Functional studies demonstrate reduced glucose uptake and cerebral perfusion in frontal, parietal, and temporal lobes, and abnormal fMRI connectivity patterns that correlate with personality traits. There is significant between-study heterogeneity in terms of imaging methods, which together with the established clinical variability of DM1 may explain divergent results. Longitudinal studies are remarkably scarce.
CONCLUSIONS
DM1 brains show widespread white and gray matter involvement throughout the brain, which is supported by abnormal resting-state network, PET/SPECT, and MRS parameters. Longitudinal studies evaluating spatiotemporal imaging changes are essential.
Topics: Brain; Humans; Myotonic Dystrophy; Neuroimaging
PubMed: 28768849
DOI: 10.1212/WNL.0000000000004300 -
Neuropathology : Official Journal of... Feb 2021Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative...
Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative of widespread grey and white matter involvement. The aim of the present study was to systematically review the literature on brain pathology in DM1. We conducted a structured search in EMBASE (index period 1974-2017) and MEDLINE (index period 1887-2017) on December 11, 2017, using free text and index search terms related to myotonic dystrophy type 1 and brain structures or regions. Eligible studies were full-text studies reporting on microscopic brain pathology of DM1 patients without potentially interfering comorbidity. We discussed the findings based on the anatomical region and the nature of the anomaly. Neuropathological findings in DM1 can be classified as follows: (1) protein and nucleotide deposits; (2) changes in neurons and glial cells; and (3) white matter alterations. Most findings are unspecific to DM1 and may occur with physiological aging, albeit to a lesser degree. There are similarities and contrasts with Alzheimer's disease; both show the appearance of neurofibrillary tangles in the limbic system without plaque occurrence. Likewise, there is myelin loss and gliosis, and there are dilated perivascular spaces in the white matter resemblant of cerebral small vessel disease. However, we did not find evidence of lacunar infarction or microbleeding. The various neuropathological findings in DM1 are reflective of the heterogeneous clinical and neuroimaging features of the disease. The strength of conclusions from this study's findings is bounded by limited numbers of participants in studies, methodological constraints, and lack of assessed associations between histopathology and clinical or neuroimaging findings.
Topics: Brain; Gray Matter; Humans; Inclusion Bodies; Myotonic Dystrophy; Neurofibrillary Tangles; Neuroimaging; White Matter
PubMed: 33599033
DOI: 10.1111/neup.12721 -
Dysphagia Jun 2014A systematic review was conducted to investigate the pathophysiology of and diagnostic procedures for oropharyngeal dysphagia in myotonic dystrophy (MD). The electronic... (Review)
Review
A systematic review was conducted to investigate the pathophysiology of and diagnostic procedures for oropharyngeal dysphagia in myotonic dystrophy (MD). The electronic databases Embase, PubMed, and The Cochrane Library were used. The search was limited to English, Dutch, French, German, Spanish, and Portuguese publications. Sixteen studies met the inclusion criteria. Two independent reviewers assessed the methodological quality of the included articles. Swallowing assessment tools, the corresponding protocols, the studies' outcome measurements, and main findings are summarized and presented. The body of literature on pathophysiology of swallowing in dysphagic patients with MD type 1 remains scant. The included studies are heterogeneous with respect to design and outcome measures and hence are not directly comparable. More importantly, most studies had methodological problems. These are discussed in detail and recommendations for further research on diagnostic examinations for swallowing disorders in patients with MD type 1 are provided.
Topics: Barium Sulfate; Contrast Media; Deglutition; Deglutition Disorders; Endoscopy; Fluoroscopy; Humans; Interviews as Topic; Manometry; Medical History Taking; Myotonic Dystrophy; Radionuclide Imaging; Surveys and Questionnaires
PubMed: 24458731
DOI: 10.1007/s00455-013-9510-9 -
Neuromuscular Disorders : NMD Mar 2019Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies in adults. This review summarises the current literature regarding the natural history of...
Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies in adults. This review summarises the current literature regarding the natural history of respiratory dysfunction in DM1, the role of central respiratory drive and peripheral respiratory muscle involvement and its significance in respiratory function, and investigates the relationship between genetics (CTG repeat length) and respiratory dysfunction. The review included all articles that reported spirometry on 10 or more myotonic dystrophy patients. The final review included 55 articles between 1964 and 2017. The major conclusions of this review were (1) confirmation of the current consensus that respiratory dysfunction, predominantly a restrictive ventilatory pattern, is common in myotonic dystrophy and is associated with alveolar hypoventilation, chronic hypercapnia, and sleep disturbance in the form of sleep apnoea and sleep related disordered breathing; (2) contrary to commonly held belief, there is no consensus in the literature regarding the relationship between CTG repeat length and severity of respiratory dysfunction and a relationship has not been established; (3) the natural history and time-course of respiratory functional decline is very poorly understood in the current literature; (4) there is a consensus that there is a significant involvement of central respiratory drive in this alveolar hypoventilation however the current literature does not identify the mechanism for this.
Topics: Humans; Hypercapnia; Myotonic Dystrophy; Respiration Disorders; Respiratory Muscles; Sleep Wake Disorders; Trinucleotide Repeat Expansion
PubMed: 30765255
DOI: 10.1016/j.nmd.2018.12.002 -
Neuromuscular Disorders : NMD Apr 2021Cardiac involvement is recorded in about 80% of patients affected by myotonic dystrophy type 1 (DM1). The prevalence of cardiac conduction abnormalities is well...
Cardiac involvement is recorded in about 80% of patients affected by myotonic dystrophy type 1 (DM1). The prevalence of cardiac conduction abnormalities is well described. Data regarding the prevalence of atrial fibrillation (AF) are still conflicting. The primary objective of this review was to assess the prevalence of AF in DM1. The secondary aim was to examine the association of clinical features with AF, to detect predisposing and/or influencing prognosis factors. A systematic search was developed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials and Web of Science databases, to identify original reports between January 1, 2002 and January 30, 2020, assessing the prevalence of AF in DM1 population. Retrospective/prospective cohort studies and case series describing the prevalence of atrial fibrillation evaluated by periodic electrocardiogram (ECG) and/or ECG Holter 24 h, external loop recording (ELR) and implantable devices interrogation in DM1 patients were included. Case reports, simple reviews, commentaries and editorials were excluded. Thirteen reports fulfilled eligibility criteria and were included in our systematic review. According to the results from all the evaluated studies, the mean prevalence of AF in DM1 patients was 10.9% (n = 404) in 3677 DM1 patients. Male sex, conduction defects, echocardiographic findings of prolonged atrial electromechanical delay seem to be strongly associated with atrial fibrillation, representing factors favoring its onset. DM1 patients who develop AF seem to have a higher risk of cardiovascular and non-cardiovascular death. Further studies are needed to assess the prevalence of AF in DM1 patients and to investigate ECG abnormalities and other clinical features associated with this condition.
Topics: Adult; Atrial Fibrillation; Case-Control Studies; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Myotonic Dystrophy; Prevalence; Prospective Studies; Retrospective Studies; Young Adult
PubMed: 33573883
DOI: 10.1016/j.nmd.2021.01.002 -
Neuromuscular Disorders : NMD Dec 2010The complexity and variability of disease manifestations in myotonic dystrophy (DM1) pose a challenge for the clinical management of patients. The follow-up of DM1...
The complexity and variability of disease manifestations in myotonic dystrophy (DM1) pose a challenge for the clinical management of patients. The follow-up of DM1 patients has been described as fragmented, inadequate or even deficient for many patients. Through a systematic review of the medical and social literature and a validation process with a DM1 expert panel, we summarized systemic and social concerns clinically relevant to DM1 and revisited recommendations for treatment. This article summarizes common manifestations of the central nervous system, visual, respiratory, cardiac, gastro-intestinal, genito-urinary, muscular and metabolic impairments. In addition, we emphasized the social features of DM1 such as low education attainment, low employment, poor familial and social environment and poor social participation. While cardiac, respiratory and swallowing problems affect life expectancy, it is often excessive daytime sleepiness, fatigue, gastro-intestinal and cognitive behavioural manifestations that are the most disabling features of the disorder. A more holistic approach in the management of DM1 and a purposeful integrated organization of care involving all members of the patients' environment including family, clinicians, decision-makers and community organizations are needed to move out of the spiral of disease and handicap and move toward optimal citizenship and quality of life.
Topics: Adult; Humans; Myotonic Dystrophy; Severity of Illness Index; Social Environment; Social Participation
PubMed: 20884209
DOI: 10.1016/j.nmd.2010.08.006 -
The Cochrane Database of Systematic... May 2021The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health...
BACKGROUND
The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health conditions, international guidance advises being as physically active as possible. Evidence from community interventions of physical activity indicate that people living with medical conditions are sometimes excluded from participation in studies. In this review, we considered the effects of activity-promoting interventions on physical activity and well-being in studies, as well as any adverse events experienced by participants living with inherited or acquired neuromuscular diseases (NMDs). OBJECTIVES: To assess the effects of interventions designed to promote physical activity in people with NMD compared with no intervention or alternative interventions.
SEARCH METHODS
On 30 April 2020, we searched Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, and ClinicalTrials.Gov. WHO ICTRP was not accessible at the time.
SELECTION CRITERIA
We considered randomised or quasi-randomised trials, including cross-over trials, of interventions designed to promote physical activity in people with NMD compared to no intervention or alternative interventions. We specifically included studies that reported physical activity as an outcome measure. Our main focus was studies in which promoting physical activity was a stated aim but we also included studies in which physical activity was assessed as a secondary or exploratory outcome.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane procedures.
MAIN RESULTS
The review included 13 studies (795 randomised participants from 12 studies; number of participants unclear in one study) of different interventions to promote physical activity. Most studies randomised a minority of invited participants. No study involved children or adolescents and nine studies reported minimal entry criteria for walking. Participants had one of nine inherited or acquired NMDs. Types of intervention included structured physical activity support, exercise support (as a specific form of physical activity), and behaviour change support that included physical activity or exercise. Only one included study clearly reported that the aim of intervention was to increase physical activity. Other studies reported or planned to analyse the effects of intervention on physical activity as a secondary or exploratory outcome measure. Six studies did not report results for physical activity outcomes, or the data were not usable. We judged 10 of the 13 included studies at high or unclear risk of bias from incomplete physical activity outcome reporting. We did not perform a meta-analysis for any comparison because of differences in interventions and in usual care. We also found considerable variation in how studies reported physical activity as an outcome measure. The studies that reported physical activity measurement did not always clearly report intention-to-treat (ITT) analysis or whether final assessments occurred during or after intervention. Based on prespecified measures, we included three comparisons in our summary of findings. A physical activity programme (weight-bearing) compared to no physical activity programme One study involved adults with diabetic peripheral neuropathy (DPN) and reported weekly duration of walking during and at the end of a one-year intervention using a StepWatch ankle accelerometer. Based on the point estimate and low-certainty evidence, intervention may have led to an important increase in physical activity per week; however, the 95% confidence interval (CI) included the possibility of no difference or an effect in either direction at three months (mean difference (MD) 34 minutes per week, 95% CI -92.19 to 160.19; 69 participants), six months (MD 68 minutes per week, 95% CI -55.35 to 191.35; 74 participants), and 12 months (MD 49 minutes per week, 95% CI -75.73 to 173.73; 70 participants). Study-reported effect estimates for foot lesions and full-thickness ulcers also included the possibility of no difference, a higher, or lower risk with intervention. A sensor-based, interactive exercise programme compared to no sensor-based, interactive exercise programme One study involved adults with DPN and reported duration of walking over 48 hours at the end of four weeks' intervention using a t-shirt embedded PAMSys sensor. It was not possible to draw conclusions about the effectiveness of the intervention from the very low-certainty evidence (MD -0.64 hours per 48 hours, 95% CI -2.42 to 1.13; 25 participants). We were also unable to draw conclusions about impact on the Physical Component Score (PCS) for quality of life (MD 0.24 points, 95% CI -5.98 to 6.46; 35 participants; very low-certainty evidence), although intervention may have made little or no difference to the Mental Component Score (MCS) for quality of life (MD 5.10 points, 95% CI -0.58 to 10.78; 35 participants; low-certainty evidence). A functional exercise programme compared to a stretching exercise programme One study involved adults with spinal and bulbar muscular atrophy and reported a daily physical activity count at the end of 12 weeks' intervention using an Actical accelerometer. It was not possible to draw conclusions about the effectiveness of either intervention (requiring compliance) due to low-certainty evidence and unconfirmed measurement units (MD -8701, 95% CI -38,293.30 to 20,891.30; 43 participants). Functional exercise may have made little or no difference to quality of life compared to stretching (PCS: MD -1.10 points, 95% CI -5.22 to 3.02; MCS: MD -1.10 points, 95% CI -6.79 to 4.59; 49 participants; low-certainty evidence). Although studies reported adverse events incompletely, we found no evidence of supported activity increasing the risk of serious adverse events.
AUTHORS' CONCLUSIONS
We found a lack of evidence relating to children, adolescents, and non-ambulant people of any age. Many people living with NMD did not meet randomised controlled trial eligibility criteria. There was variation in the components of supported activity intervention and usual care, such as physical therapy provision. We identified variation among studies in how physical activity was monitored, analysed, and reported. We remain uncertain of the effectiveness of promotional intervention for physical activity and its impact on quality of life and adverse events. More information is needed on the ITT population, as well as more complete reporting of outcomes. While there may be no single objective measure of physical activity, the study of qualitative and dichotomous change in self-reported overall physical activity might offer a pragmatic approach to capturing important change at an individual and population level.
Topics: Bias; Exercise; Health Promotion; Humans; Muscle Stretching Exercises; Neuromuscular Diseases; Outcome Assessment, Health Care; Quality of Life; Randomized Controlled Trials as Topic; Resistance Training; Time Factors; Walking
PubMed: 34027632
DOI: 10.1002/14651858.CD013544.pub2 -
Cureus Dec 2021Cobb's tufts, also known as iris vascular tufts (IVT) and iris microhemangiomas (IMH), are coils of tightly clustered, minute blood vessels at the iris... (Review)
Review
Cobb's tufts, also known as iris vascular tufts (IVT) and iris microhemangiomas (IMH), are coils of tightly clustered, minute blood vessels at the iris pupillary border. This study aimed to analyze previous literature and provide an update on Cobb's tufts. A systematic literature review was carried out by interrogating PubMed, Google Scholar, Cochrane, and Embase databases. Full-text English language articles of any year were included in this study. A total of 38 articles fulfilled our inclusion criteria. A total of 115 reported cases of Cobb's tufts were incorporated into our review. The age of the patients ranged between 36 and 86 years. No sex or racial predisposition was noted. Most patients had no history of trauma, surgery, or blood dyscrasia. The majority of cases are asymptomatic and bilateral unless a spontaneous hyphema occurs, which most commonly presents as blurred vision. The etiology of this condition remains uncertain; however, a higher incidence has been shown in systemic conditions such as myotonic dystrophy and diabetes. Fluorescein angiography can be utilized to investigate tufts. Management includes treatment of raised intraocular pressure, observation for single bleeds, laser therapy for recurrent hyphemas, and lastly, iridectomy, which is considered in cases of recurrence following laser treatment.
PubMed: 35003982
DOI: 10.7759/cureus.20151