Project description:Type 2 diabetes (T2D) is a strong, independent risk factor for cardiovascular (CV) and cerebrovascular outcomes. Meta-analysis of five randomised clinical trials (n = 33,040) showed that, although intensive versus standard glycaemic control significantly reduced CV events in people with T2D, the reduction was less than that achieved with lipid-lowering or antihypertensive treatment. Furthermore, fasting plasma glucose (FPG) concentrations were a modest predictor for CV risk in people without T2D. Thus, although effective glycaemic control is important for the prevention/management of T2D, other risk factors must be addressed to effectively reduce CV risk. Reducing low-density lipoprotein-cholesterol levels using statins significantly reduces CV risk in people with and without T2D. Although statins are generally safe and well tolerated, conflicting data exist regarding the diabetogenic effects of some statins. Based on recent clinical trial data, the US Food and Drug Administration have changed the labelling of all statins to include 'an effect of statins on incident diabetes and increases in haemoglobin A1c and/or FPG'. However, the literature suggests that the beneficial effects of most statins on CV risk continue to outweigh their diabetogenic risks and that statins should remain as first-line therapy for the majority of people with dyslipidaemia and metabolic syndrome or T2D. Mechanisms explaining the potentially higher incidence of T2D with statin therapy have not been confirmed. However, independent predictors for statin-associated T2D appear to include elevated levels of baseline FPG, BMI, blood pressure and fasting triglycerides. Moreover, although some statins (for example, atorvastatin) are associated with increased haemoglobin A1c levels in patients receiving intensive but not moderate therapy, other statins (for example, pitavastatin) have demonstrated neutral or favourable effects on glucose control in patients with and without T2D or metabolic syndrome. The potential diabetogenic effects of statins may therefore differ between drugs. In conclusion, conflicting data exist regarding the diabetogenic effects of statins. Further studies are required to understand whether all statins have the same effect and whether some patient groups are at higher risk than others. Meanwhile, results suggest that the net CV benefit favours the use of statin therapy in patients with dyslipidaemia, irrespective of T2D risk.

Project description:BackgroundBreathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers.MethodsFemale patients with a clinical diagnosis of typical RTT (n = 66), MECP2 gene mutation, and apneas were enrolled (mean age: 12.5 years). Baseline clinical severity, arterial blood gas analysis, and red blood cell count were assessed. Breathing was monitored during the wakefulness and sleep states (average recording time: 13 ± 0.5 h) with a portable polygraphic screening device. According to prevalence of breath holdings, the population was categorized into the wakefulness apnea (WA) and sleep apnea (SA) groups, and apnea-hypopnea index (AHI) was calculated. The impact of respiratory events on oxidative stress was assessed by plasma and intra-erythrocyte non-protein-bound iron (P-NPBI and IE-NPBI, respectively), and plasma F2-isoprostane (F2-IsoP) assays.ResultsSignificant prevalence of obstructive apneas with values of AHI > 15 was present in 69.7% of the population with RTT. The group with SA showed significantly increased AHI values > 15 (p = 0.0032), total breath holding episodes (p = 0.007), and average SpO2 (p = 0.0001) as well as lower nadir SpO2 (p = 0.0004) compared with the patients with WAs. The subgroups of patients with WA and SA showed no significant differences in arterial blood gas analysis variables (p > 0.089). Decreased mean cell hemoglobin (MCH) (p = 0.038) was observed in the group with WAs. P-NPBI levels were significantly higher in the group with WA than in that with SAs (p = 0.0001). Stepwise multiple linear regression models showed WA being related to nadir SpO2, average SpO2, and P-NPBI (adjusted R 2 = 0.613, multiple correlation coefficient = 0.795 p < 0.0001), and P-NPBI being related to average SpO2, blood PaCO2, red blood cell mean corpuscular volume (MCV), age, and topiramate treatment (adjusted R 2 = 0.551, multiple correlation coefficient = 0.765, p < 0.0001).ConclusionOur findings indicate that the impact of apneas in RTT is uneven according to the sleep-wakefulness cycle, and that plasma redox active iron represents a potential novel therapeutic target.

Project description:Rationale: Sleep-disordered breathing (SDB) occurring primarily during rapid eye movement (REM) sleep is a common clinical problem. The natural history of REM-related SDB and the associated cardiovascular sequelae of disease progression remain to be determined.Objectives: The objective of the current study was to describe the natural history of REM-related SDB, ascertain predictors of progression, and determine whether the evolution of REM-related SDB into non-REM (NREM) sleep is associated with incident cardiovascular events.Methods: Participants from the Sleep Heart Health Study with a baseline NREM apnea-hypopnea index (NREM-AHI) of <5 events/h and data from a follow-up sleep study along with information on incident cardiovascular disease were included in the study. Bivariate logistic regression was used to jointly model the predictors of disease progression based on the presence or absence of SDB during NREM and REM sleep using a cut-point of 5 events/h. Explanatory variables such as age, race, body mass index (BMI), change in BMI, and baseline REM-AHI were considered. Proportional hazards regression was then used to establish whether the development of SDB during NREM sleep was associated with incident cardiovascular disease.Results: The majority of the 1,908 participants included in the study did not develop SDB during NREM sleep. The likelihood of progression of SDB into NREM sleep did increase with higher baseline REM-AHI. BMI and an increase in BMI predicted progression of SDB in both NREM and REM sleep in men but not in women. There was a strong interdependence between developing a NREM-AHI of ≥5 events/h and worsening REM-AHI at follow-up with odds ratios of 6.01 and 4.47, in women and men, respectively. Moreover, the relative risk for incident cardiovascular events among those who developed a NREM-AHI of ≥5 events/h at the follow-up visit was elevated only in women with REM-related SDB at baseline.Conclusions: SDB during REM sleep is a relatively stable condition and does not progress in the majority of individuals. Progression of SDB into NREM sleep is associated with sex, weight, and age. SDB during REM and NREM sleep tends to develop concurrently. Finally, the development of SDB during NREM sleep is associated with incident cardiovascular events, but only in women with REM-related SDB at baseline.

Project description:BackgroundThe coronavirus disease (COVID-19) presents unique challenges in health care, including mental health care provision. Telepsychiatry can provide an alternative to face-to-face assessment and can also be used creatively with other technologies to enhance care, but clinicians and patients may feel underconfident about embracing this new way of working.ObjectiveThe aim of this paper is to produce an open-access, easy-to-consult, and reliable source of information and guidance about telepsychiatry and COVID-19 using an evidence-based approach.MethodsWe systematically searched existing English language guidelines and websites for information on telepsychiatry in the context of COVID-19 up to and including May 2020. We used broad search criteria and included pre-COVID-19 guidelines and other digital mental health topics where relevant. We summarized the data we extracted as answers to specific clinical questions.ResultsFindings from this study are presented as both a short practical checklist for clinicians and detailed textboxes with a full summary of all the guidelines. The summary textboxes are also available on an open-access webpage, which is regularly updated. These findings reflected the strong evidence base for the use of telepsychiatry and included guidelines for many of the common concerns expressed by clinicians about practical implementation, technology, information governance, and safety. Guidelines across countries differ significantly, with UK guidelines more conservative and focused on practical implementation and US guidelines more expansive and detailed. Guidelines on possible combinations with other digital technologies such as apps (eg, from the US Food and Drug Administration, the National Health Service Apps Library, and the National Institute for Health and Care Excellence) are less detailed. Several key areas were not represented. Although some special populations such as child and adolescent, and older adult, and cultural issues are specifically included, important populations such as learning disabilities, psychosis, personality disorder, and eating disorders, which may present particular challenges for telepsychiatry, are not. In addition, the initial consultation and follow-up sessions are not clearly distinguished. Finally, a hybrid model of care (combining telepsychiatry with other technologies and in-person care) is not explicitly covered by the existing guidelines.ConclusionsWe produced a comprehensive synthesis of guidance answering a wide range of clinical questions in telepsychiatry. This meets the urgent need for practical information for both clinicians and health care organizations who are rapidly adapting to the pandemic and implementing remote consultation. It reflects variations across countries and can be used as a basis for organizational change in the short- and long-term. Providing easily accessible guidance is a first step but will need cultural change to implement as clinicians start to view telepsychiatry not just as a replacement but as a parallel and complementary form of delivering therapy with its own advantages and benefits as well as restrictions. A combination or hybrid approach can be the most successful approach in the new world of mental health post-COVID-19, and guidance will need to expand to encompass the use of telepsychiatry in conjunction with other in-person and digital technologies, and its use across all psychiatric disorders, not just those who are the first to access and engage with remote treatment.

Project description:RationaleSleep-disordered breathing recurrent intermittent hypoxia and sympathetic nervous system activity surges provide the milieu for cardiac arrhythmia development.ObjectiveWe postulate that the prevalence of nocturnal cardiac arrhythmias is higher among subjects with than without sleep-disordered breathing.MethodsThe prevalence of arrhythmias was compared in two samples of participants from the Sleep Heart Health Study frequency-matched on age, sex, race/ethnicity, and body mass index: (1) 228 subjects with sleep-disordered breathing (respiratory disturbance index>or=30) and (2) 338 subjects without sleep-disordered breathing (respiratory disturbance index<5).ResultsAtrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy (nonsustained ventricular tachycardia or bigeminy or trigeminy or quadrigeminy) were more common in subjects with sleep-disordered breathing compared with those without sleep-disordered breathing: 4.8 versus 0.9% (p=0.003) for atrial fibrillation; 5.3 versus 1.2% (p=0.004) for nonsustained ventricular tachycardia; 25.0 versus 14.5% (p=0.002) for complex ventricular ectopy. Compared with those without sleep-disordered breathing and adjusting for age, sex, body mass index, and prevalent coronary heart disease, individuals with sleep-disordered breathing had four times the odds of atrial fibrillation (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.03-15.74), three times the odds of nonsustained ventricular tachycardia (OR, 3.40; 95% CI, 1.03-11.20), and almost twice the odds of complex ventricular ectopy (OR, 1.74; 95% CI, 1.11-2.74). A significant relation was also observed between sleep-disordered breathing and ventricular ectopic beats/h (p<0.0003) considered as a continuous outcome.ConclusionsIndividuals with severe sleep-disordered breathing have two- to fourfold higher odds of complex arrhythmias than those without sleep-disordered breathing even after adjustment for potential confounders.

Project description:IntroductionObstructive sleep apnea is an important and common disorder with associated health risks. Assuring successful longitudinal management is vital to patient health and sleep-related quality of life. This paper provides guidance from the American Academy of Sleep Medicine (AASM) regarding the use of polysomnography (PSG) and home sleep apnea tests (HSATs) after a diagnosis of obstructive sleep apnea has been established and, in most cases, treatment implemented.MethodsThe AASM commissioned a task force of five sleep medicine experts. A literature search was conducted to identify studies that included adult patients with OSA who underwent follow-up PSG or an HSAT. The task force developed clinical guidance statements based on a review of these studies and expert opinion. The AASM Board of Directors approved the final clinical guidance statements.Clinical guidance statementsThe AASM supports the following clinical guidance statements on indications for follow-up PSG and HSAT in adult patients with OSA. 1. Follow-up PSG or HSAT is not recommended for routine reassessment of asymptomatic patients with obstructive sleep apnea on PAP therapy, however, follow-up PSG or HSAT can be used to reassess patients with recurrent or persistent symptoms, despite good PAP adherence. 2. Follow-up PSG or HSAT is recommended to assess response to treatment with non-PAP interventions. 3. Follow-up PSG or HSAT may be used if clinically significant weight gain or loss has occurred since diagnosis of OSA or initiation of its treatment. 4. Follow-up PSG may be used for reassessment of sleep-related hypoxemia and/or sleep-related hypoventilation following initiation of treatment for OSA. 5. Follow-up PSG or HSAT may be used in patients being treated for OSA who develop or have a change in cardiovascular disease. 6. Follow-up PSG may be used in patients with unexplained PAP device-generated data. The ultimate judgment regarding propriety of any specific care must be made by the clinician, in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options and resources.

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Clinical relevance of arrhythmias during sleep: guidance for clinicians.

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Clinical relevance of arrhythmias during sleep: guidance for clinicians.

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