Sleep disordered breathing at the extremes of age: the elderly

Key points Sleep disordered breathing (SDB) is common and its prevalence increases with age. Despite this high prevalence, SDB is frequently unrecognised and undiagnosed in older people.; There is accumulating evidence that SDB in older people is associated with worsening cardio- cerebrovascular, cognitive and functional outcomes.; There is now good evidence to support the use of continuous positive airway pressure therapy in older patients with symptomatic SDB.; Educational aims To highlight the prevalence and presentation of sleep disordered breathing (SDB) in older people.; To inform readers about the risk factors for SDB in older people.; To explore the impact of SDB in older people.; To introduce current evidence based treatment options for SDB in older people.; Sleep disordered breathing (SBD) increases in prevalence as we age, most likely due to physiological and physical changes that occur with ageing. Additionally, SDB is associated with comorbidity and its subsequent polypharmacy, which may increase with increasing age. Finally, the increased prevalence of SDB is intrinsically linked to the obesity epidemic. SDB is associated with serious outcomes in younger people and, likewise, older people. Thus, identification, diagnosis and treatment of SDB is important irrelevant of age. This article reviews the age-related changes contributing to SDB, the epidemiology and the risk factors for SDB in older people, the association of SDB with adverse outcomes, and diagnostic and treatment options for this population

Investigation of the link between fluid shift and airway collapsibility as a mechanism for obstructive sleep apnea in congestive heart failure

The increased prevalence of obstructive sleep apnea (OSA) in congestive heart failure (CHF) may be associated with rostral fluid shift. We investigated the effect of overnight rostral fluid shift on pharyngeal collapsibility (Pcrit), pharyngeal caliber (APmean), and apnea‐hypopnea index (AHI) in CHF patients. Twenty‐three optimally treated systolic CHF patients were studied. Neck circumference was measured immediately prior to sleep in the evening and immediately after waking in the morning as a marker of rostral fluid shift. Pcrit was measured during sleep, early and late in the night. APmean was measured using acoustic reflection at the same times as neck circumference measurements. 15/23 CHF patients experienced an overnight increase in neck circumference; overall neck circumference significantly increased overnight (mean±SD, evening: 41.7 ± 3.2 cm; morning: 42.3 ± 3.1 cm; P = 0.03). Pcrit increased significantly overnight (early‐night: −3.8 ± 3.3 cmH2O; late‐night: −2.6 ± 3.0 cmH2O; P = 0.03) and APmean decreased (evening: 4.2 ± 1.3 cm2; morning: 3.7 ± 1.3 cm2; P = 0.006). The total AHI correlated with neck circumference (r = 0.4; P = 0.04) and Pcrit (r = 0.5; P = 0.01). APmean correlated with neck circumference (r = −0.47; P = 0.02). There was no significant change in AHI between the first and second half of the night (first‐half: 12.9 ± 12.4/h; second‐half: 13.7 ± 13.3/h; P = 0.6). Overnight rostral fluid shift was associated with increased pharyngeal collapsibility and decreased pharyngeal caliber during sleep in CHF patients. Rostral fluid shift may be an important mechanism of OSA in this patient group

A novel in-ear sensor to determine sleep latency during the Multiple Sleep Latency Test in healthy adults with and without sleep restriction

Objectives: Detecting sleep latency during the Multiple Sleep Latency Test (MSLT) using electroencephalogram (scalp-EEG) is time-consuming. The aim of this study was to evaluate the efficacy of a novel in-ear sensor (in-ear EEG) to detect the sleep latency, compared to scalp-EEG, during MSLT in healthy adults, with and without sleep restriction. Methods: We recruited 25 healthy adults (28.5±5.3 years) who participated in two MSLTs with simultaneous recording of scalp and in-ear EEG. Each test followed a randomly assigned sleep restriction (≤5 hours sleep) or usual night sleep (≥7 hours sleep). Reaction time and Stroop test were used to assess the functional impact of the sleep restriction. The EEGs were scored blind to the mode of measurement and study conditions, using American Academy of Sleep Medicine 2012 criteria. The Agreement between the scalp and in-ear EEG was assessed using Bland-Altman analysis. Results: Technically acceptable data were obtained from 23 adults during 69 out of 92 naps in the sleep restriction condition and 25 adults during 85 out of 100 naps in the usual night sleep. Meaningful sleep restrictions were confirmed by an increase in the reaction time (mean ± SD: 238±30 ms vs 228±27 ms; P=0.045). In the sleep restriction condition, the in-ear EEG exhibited a sensitivity of 0.93 and specificity of 0.80 for detecting sleep latency, with a substantial agreement (κ=0.71), whereas after the usual night’s sleep, the in-ear EEG exhibited a sensitivity of 0.91 and specificity of 0.89, again with a substantial agreement (κ=0.79). Conclusion: The in-ear sensor was able to detect reduced sleep latency following sleep restriction, which was sufficient to impair both the reaction time and cognitive function. Substantial agreement was observed between the scalp and in-ear EEG when measuring sleep latency. This new in-ear EEG technology is shown to have a significant value as a convenient measure for sleep latency

A survey of statistics in three UK general practice journal

Background Many medical specialities have reviewed the statistical content of their journals. To our knowledge this has not been done in general practice. Given the main role of a general practitioner as a diagnostician we thought it would be of interest to see whether the statistical methods reported reflect the diagnostic process. Methods Hand search of three UK journals of general practice namely the British Medical Journal (general practice section), British Journal of General Practice and Family Practice over a one-year period (1 January to 31 December 2000). Results A wide variety of statistical techniques were used. The most common methods included t-tests and Chi-squared tests. There were few articles reporting likelihood ratios and other useful diagnostic methods. There was evidence that the journals with the more thorough statistical review process reported a more complex and wider variety of statistical techniques. Conclusions The BMJ had a wider range and greater diversity of statistical methods than the other two journals. However, in all three journals there was a dearth of papers reflecting the diagnostic process. Across all three journals there were relatively few papers describing randomised controlled trials thus recognising the difficulty of implementing this design in general practice

Diagnosis of sleep apnoea using a mandibular monitor and machine learning analysis: one-night agreement compared to in-home polysomnography

Background: The capacity to diagnose obstructive sleep apnoea (OSA) must be expanded to meet an estimated disease burden of nearly one billion people worldwide. Validated alternatives to the gold standard polysomnography (PSG) will improve access to testing and treatment. This study aimed to evaluate the diagnosis of OSA, using measurements of mandibular movement (MM) combined with automated machine learning analysis, compared to in-home PSG. Methods: 40 suspected OSA patients underwent single overnight in-home sleep testing with PSG (Nox A1, ResMed, Australia) and simultaneous MM monitoring (Sunrise, Sunrise SA, Belgium). PSG recordings were manually analysed by two expert sleep centres (Grenoble and London); MM analysis was automated. The Obstructive Respiratory Disturbance Index calculated from the MM monitoring (MM-ORDI) was compared to the PSG (PSG-ORDI) using intraclass correlation coefficient and Bland-Altman analysis. Receiver operating characteristic curves (ROC) were constructed to optimise the diagnostic performance of the MM monitor at different PSG-ORDI thresholds (5, 15, and 30 events/hour). Results: 31 patients were included in the analysis (58% men; mean (SD) age: 48 (15) years; BMI: 30.4 (7.6) kg/m2). Good agreement was observed between MM-ORDI and PSG-ORDI (median bias 0.00; 95% CI −23.25 to + 9.73 events/hour). However, for 15 patients with no or mild OSA, MM monitoring overestimated disease severity (PSG-ORDI 5–15: MM-ORDI overestimation + 3.70 (95% CI −0.53 to + 18.32) events/hour). In 16 patients with moderate-severe OSA (n = 9 with PSG-ORDI 15–30 events/h and n = 7 with a PSG-ORD > 30 events/h), there was an underestimation (PSG-ORDI > 15: MM-ORDI underestimation −8.70 (95% CI −28.46 to + 4.01) events/hour). ROC optimal cut-off values for PSG-ORDI thresholds of 5, 15, 30 events/hour were: 9.53, 12.65 and 24.81 events/hour, respectively. These cut-off values yielded a sensitivity of 88, 100 and 79%, and a specificity of 100, 75, 96%. The positive predictive values were: 100, 80, 95% and the negative predictive values 89, 100, 82%, respectively. Conclusion: The diagnosis of OSA, using MM with machine learning analysis, is comparable to manually scored in-home PSG. Therefore, this novel monitor could be a convenient diagnostic tool that can easily be used in the patients’ own home. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT0426255

Development of genome-specific primers for homoeologous genes in allopolyploid species: the waxy and starch synthase II genes in allohexaploid wheat (Triticum aestivum L.) as examples

<p>Abstract</p> <p>Background</p> <p>In allopolypoid crops, homoeologous genes in different genomes exhibit a very high sequence similarity, especially in the coding regions of genes. This makes it difficult to design genome-specific primers to amplify individual genes from different genomes. Development of genome-specific primers for agronomically important genes in allopolypoid crops is very important and useful not only for the study of sequence diversity and association mapping of genes in natural populations, but also for the development of gene-based functional markers for marker-assisted breeding. Here we report on a useful approach for the development of genome-specific primers in allohexaploid wheat.</p> <p>Findings</p> <p>In the present study, three genome-specific primer sets for the <it>waxy </it>(<it>Wx</it>) genes and four genome-specific primer sets for the <it>starch synthase II </it>(<it>SSII</it>) genes were developed mainly from single nucleotide polymorphisms (SNPs) and/or insertions or deletions (Indels) in introns and intron-exon junctions. The size of a single PCR product ranged from 750 bp to 1657 bp. The total length of amplified PCR products by these genome-specific primer sets accounted for 72.6%-87.0% of the <it>Wx </it>genes and 59.5%-61.6% of the <it>SSII </it>genes. Five genome-specific primer sets for the <it>Wx </it>genes (one for Wx-7A, three for Wx-4A and one for Wx-7D) could distinguish the wild type wheat and partial waxy wheat lines. These genome-specific primer sets for the <it>Wx </it>and <it>SSII </it>genes produced amplifications in hexaploid wheat, cultivated durum wheat, and <it>Aegilops tauschii </it>accessions, but failed to generate amplification in the majority of wild diploid and tetraploid accessions.</p> <p>Conclusions</p> <p>For the first time, we report on the development of genome-specific primers from three homoeologous <it>Wx </it>and <it>SSII </it>genes covering the majority of the genes in allohexaploid wheat. These genome-specific primers are being used for the study of sequence diversity and association mapping of the three homoeologous <it>Wx </it>and <it>SSII </it>genes in natural populations of both hexaploid wheat and cultivated tetraploid wheat. The strategies used in this paper can be used to develop genome-specific primers for homoeologous genes in any allopolypoid species. They may be also suitable for (i) the development of gene-specific primers for duplicated paralogous genes in any diploid species, and (ii) the development of allele-specific primers at the same gene locus.</p

Effect of lifestyle intervention for people with diabetes or prediabetes in real-world primary care: propensity score analysis

<p>Abstract</p> <p>Background</p> <p>Many lifestyle interventions for patients with prediabetes or type 2 diabetes mellitus (T2DM) have been investigated in randomised clinical trial settings. However, the translation of these programmes into primary care seems challenging and the prevalence of T2DM is increasing. Therefore, there is an urgent need for lifestyle programmes, developed and shown to be effective in real-world primary care. We evaluated a lifestyle programme, commissioned by the Dutch government, for patients with prediabetes or type 2 diabetes in primary care.</p> <p>Methods</p> <p>We performed a retrospective comparative medical records analysis using propensity score matching. Patients with prediabetes or T2DM were selected from ten primary healthcare centres. Patients who received the lifestyle intervention (n = 186) were compared with a matched group of patients who received usual care (n = 2632). Data were extracted from the electronic primary care records. Propensity score matching was used to control for confounding by indication. Outcome measures were exercise level, BMI, HbA1c, fasting glucose, systolic and diastolic blood pressure, total cholesterol, HDL and LDL cholesterol and triglycerides and the follow-up period was one year.</p> <p>Results</p> <p>There was no significant difference at follow-up in any outcome measure between either group. The reduction at one year follow-up of HbA1c and fasting glucose was positive in the intervention group compared with controls, although not statistically significant (-0.12%, <it>P </it>= 0.07 and -0.17 mmol/l, <it>P </it>= 0.08 respectively).</p> <p>Conclusions</p> <p>The effects of the lifestyle programme in real-world primary care for patients with prediabetes or T2DM were small and not statistically significant. The attention of governments for lifestyle interventions is important, but from the available literature and the results of this study, it must be concluded that improving lifestyle in real-world primary care is still challenging.</p

Recommendations for the analysis of individually randomised controlled trials with clustering in one arm - a case of continuous outcomes

BACKGROUND: In an individually randomised controlled trial where the treatment is delivered by a health professional it seems likely that the effectiveness of the treatment, independent of any treatment effect, could depend on the skill, training or even enthusiasm of the health professional delivering it. This may then lead to a potential clustering of the outcomes for patients treated by the same health professional, but similar clustering may not occur in the control arm. Using four case studies, we aim to provide practical guidance and recommendations for the analysis of trials with some element of clustering in one arm. METHODS: Five approaches to the analysis of outcomes from an individually randomised controlled trial with clustering in one arm are identified in the literature. Some of these methods are applied to four case studies of completed randomised controlled trials with clustering in one arm with sample sizes ranging from 56 to 539. Results are obtained using the statistical packages R and Stata and summarised using a forest plot. RESULTS: The intra-cluster correlation coefficient (ICC) for each of the case studies was small (<0.05) indicating little dependence on the outcomes related to cluster allocations. All models fitted produced similar results, including the simplest approach of ignoring clustering for the case studies considered. CONCLUSIONS: A partially clustered approach, modelling the clustering in just one arm, most accurately represents the trial design and provides valid results. Modelling homogeneous variances between the clustered and unclustered arm is adequate in scenarios similar to the case studies considered. We recommend treating each participant in the unclustered arm as a single cluster. This approach is simple to implement in R and Stata and is recommended for the analysis of trials with clustering in one arm only. However, the case studies considered had small ICC values, limiting the generalisability of these results

Characterization of the linkage disequilibrium structure and identification of tagging-SNPs in five DNA repair genes

BACKGROUND: Characterization of the linkage disequilibrium (LD) structure of candidate genes is the basis for an effective association study of complex diseases such as cancer. In this study, we report the LD and haplotype architecture and tagging-single nucleotide polymorphisms (tSNPs) for five DNA repair genes: ATM, MRE11A, XRCC4, NBS1 and RAD50. METHODS: The genes ATM, MRE11A, and XRCC4 were characterized using a panel of 94 unrelated female subjects (47 breast cancer cases, 47 controls) obtained from high-risk breast cancer families. A similar LD structure and tSNP analysis was performed for NBS1 and RAD50, using publicly available genotyping data. We studied a total of 61 SNPs at an average marker density of 10 kb. Using a matrix decomposition algorithm, based on principal component analysis, we captured >90% of the intragenetic variation for each gene. RESULTS: Our results revealed that three of the five genes did not conform to a haplotype block structure (MRE11A, RAD50 and XRCC4). Instead, the data fit a more flexible LD group paradigm, where SNPs in high LD are not required to be contiguous. Traditional haplotype blocks assume recombination is the only dynamic at work. For ATM, MRE11A and XRCC4 we repeated the analysis in cases and controls separately to determine whether LD structure was consistent across breast cancer cases and controls. No substantial difference in LD structures was found. CONCLUSION: This study suggests that appropriate SNP selection for an association study involving candidate genes should allow for both mutation and recombination, which shape the population-level genomic structure. Furthermore, LD structure characterization in either breast cancer cases or controls appears to be sufficient for future cancer studies utilizing these genes