Neurocognitive function in obstructive sleep apnoea: A meta‐review

Adult obstructive sleep apnoea (OSA) is associated with cognitive dysfunction. While many review articles have attempted to summarize the evidence for this association, it remains difficult to determine which domains of cognition are affected by OSA. This is because of marked differences in the nature of these reviews (e.g. many are unsystematic) and the many different tasks and domains assessed. This paper addresses this issue by comparing the results of only systematic reviews or meta‐analyses assessing the effects of OSA on cognition, the relationship between OSA severity and cognition, and/or the effects of treatment on cognition in OSA. Electronic databases and hand‐searching were undertaken to select reviews that reported on these areas. We found 33 reviews; five reviews met predetermined, stringent selection criteria. The majority of reviews supported deficits in attention/vigilance, delayed long‐term visual and verbal memory, visuospatial/constructional abilities, and executive function in individuals with OSA. There is also general agreement that language ability and psychomotor function are unaffected by OSA. Data are equivocal for the effects of OSA on working memory, short‐term memory and global cognitive functioning. Attention/vigilance dysfunction appears to be associated with sleep fragmentation and global cognitive function with hypoxaemia. Continuous positive airway pressure treatment of OSA appears to improve executive dysfunction, delayed long‐term verbal and visual memory, attention/vigilance and global cognitive functioning. In order to improve our understanding of cognitive dysfunction in OSA, future research should pay particular attention to participant characteristics, measures of disease severity and choice of neuropsychological tests.     

Obstructive sleep apnoea and the risk of type 2 diabetes: A meta‐analysis of prospective cohort studies

Background and objective: There has been increasing recognition that obstructive sleep apnoea (OSA) is associated with incident type 2 diabetes. The aim of this study was to assess the association between the severity of OSA and the risk of type 2 diabetes by performing a meta‐analysis of all available prospective cohort studies. Methods: A search was conducted of the PubMed, EMBASE, CINAHL and ISI Web of Knowledge databases through March 2012 to identify studies linking OSA with the risk of diabetes. Only prospective cohort studies, in which the presence of OSA was confirmed by objective measurements, were included. Fixed and random effects models were used to calculate pooled relative risks (RR). Results: This meta‐analysis of six prospective cohort studies including a total of 5953 participants, with follow‐up periods of 2.7–16 years, and 332 incident cases of type 2 diabetes, showed that moderate‐severe OSA was associated with a greater risk of diabetes (RR 1.63; 95% confidence interval (CI): 1.09–2.45), as compared with the absence of OSA. Sensitivity analyses yielded similar results. For subjects with mild OSA, as compared with those without OSA, the pooled RR of developing type 2 diabetes was 1.22 (95% CI: 0.91–1.63). Conclusions: This meta‐analysis indicates that moderate‐severe OSA is associated with an increased risk of type 2 diabetes, and this appears to be an independent risk factor for the development of diabetes.     

Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: A systematic review and meta‐analysis

Obstructive sleep apnoea (OSA) is a prevalent sleep‐related breathing disorder associated with adverse cardiovascular outcome. Endothelial dysfunction is one of the proposed mechanistic links between OSA and the increased cardiovascular risk. Treatment with continuous positive airway pressure (CPAP) may reverse this detrimental pathophysiological consequence of OSA. Most studies on the effect of CPAP on endothelial function in OSA are limited by their low sample size. The objective of this systematic review was to assess the effect CPAP therapy on endothelial function in patients with OSA. We conducted a systematic review and meta‐analysis searching literature databases up to August 2013 for randomized controlled trials (RCTs) on the effect of CPAP on endothelial function in OSA, assessed by flow‐mediated dilatation (FMD) and other validated techniques. The primary outcome for the meta‐analysis (DerSimonian/Laird random‐effects method) was the treatment effect on FMD. Eight RCTs comparing the effects of therapeutic CPAP versus subtherapeutic CPAP (or no intervention) on endothelial function involving 245 OSA patients were included in the systematic review. The studies are consistent in effect direction, showing an improvement of endothelial function by CPAP. Four RCTs involving 150 patients could be used for the meta‐analysis. Compared to the control group, CPAP therapy (range 2–24 weeks) significantly increased absolute % FMD by 3.87% (95% confidence interval: 1.93–5.80, P < 0.001). In patients with OSA, CPAP therapy improves endothelial function significantly and to a clinically important extent.     

Effects of weight loss on pulmonary function in obese men with obstructive sleep apnoea syndrome

Abstract. The effects of long-term behaviour modification of obesity on pulmonary function was studied in eight men with obstructive sleep apnoea syndrome (initial mean body mass index [BMI] 41.8 kg m^?2) before and after a mean weight loss of 20 ± 7 (SD) kg. Mean arterial Pco₂ fell from 6.3 ± 1.2 to 5.5 ± 0.6 kPa (P < 0.05) and concomitant significant improvements were found in vital capacity, total lung capacity, functional residual capacity and forced expired volume (FEV 1.0). The study suggests that weight loss per se, rather than the method of choice to achieve weight loss, results in clinically significant improvement of pulmonary function in obese men.     

A nurse-managed weight reduction programme for obstructive sleep apnoea syndrome

Archimandritis A, Souyioultzis S, Katsorida M, Tzivras M (University of Athens Medical School, Laiko General Hospital, Athens, Greece). Clostridium difficile colitis associated with a ‘triple’ regimen, containing clarithromycin and metronidazole, to eradicate Helicobacter pylori (Case Report). J Intern Med 1998; 243 : 251–53. We describe a 54-year-old man with Helicobacter pylori (+) duodenal ulcer who developed Clostridium difficile associated colitis, 5 days after commencing a ‘triple’ regimen consisting of omeprazole 20 mg b.d., metronidazole 500 mg b.d. and clarithromycin 500 mg b.d., to eradicate H. pylori. Despite the fact that oral metronidazole did not prevent the disease, the patient did well after treatment with oral metronidazole plus a yeast preparation (Saccharomyces bulardii). No relapse occurred.     

Effective strategies for weight loss in post‐partum women: a systematic review and meta‐analysis

Post‐partum weight loss is critical to preventing and managing obesity in women, but the results from lifestyle interventions are variable and the components associated with successful outcomes are not yet clearly identified. This study aimed to identify lifestyle intervention strategies associated with weight loss in post‐partum women. MEDLINE, EMBASE, PubMed, CINAHL and four other databases were searched for lifestyle intervention studies (diet or exercise or both) in post‐partum women (within 12 months of delivery) published up to July 2014. The primary outcome was weight loss. Subgroup analyses were conducted for self‐monitoring, individual or group setting, intervention duration, intervention types, the use of technology as a support, and home‐ or centre‐based interventions. From 12,673 studies, 46 studies were included in systematic review and 32 randomized controlled trials were eligible for meta‐analysis (1,892 women, age 24–36 years). Studies with self‐monitoring had significantly greater weight lost than those without (?4.61 kg [?7.08, ?2.15] vs. ?1.34 kg [?1.66, ?1.02], P = 0.01 for subgroup differences). Diet and physical activity when combined were significantly more effective on weight loss compared with physical activity alone (?3.24 kg [?4.59, ?1.90] vs. ?1.63 kg [?2.16, ?1.10], P < 0.001 for subgroup differences). Lifestyle interventions that use self‐monitoring and take a combined diet‐and‐exercise approach have significantly greater weight loss in post‐partum women.     

Effects of lifestyle intervention on long‐term risk of diabetes in women with prior gestational diabetes: A systematic review and meta‐analysis of randomized controlled trials

We performed two meta‐analyses to estimate the effects of lifestyle intervention during pregnancy and after delivery on the risk of postpartum diabetes among women with gestational diabetes mellitus (GDM). We searched the major databases to retrieve articles published in English or Chinese before 15 December 2019. The inclusion criteria were randomized controlled trials (RCTs) of diet, physical activity or both, conducted during or after pregnancy among women with GDM. The exclusion criteria were (1) having type 1 or type 2 diabetes before the intervention and (2) without postpartum diabetes documented. Fixed‐effects model analysis was used to obtain the pooled relative risks (RRs) and 95% confidence intervals (CIs) of lifestyle intervention for diabetes in women with GDM. Four RCTs were identified to have implemented the intervention during pregnancy (n = 2883) and 10 to have conducted it within 3 years after delivery (n = 1733). Lifestyle intervention during pregnancy was not effective at reducing the risk of postpartum diabetes (RR: 0.91, 95%CI: 0.66–1.25). However, lifestyle intervention initiated within 3 years after delivery was highly effective in reducing the risk of postpartum diabetes (pooled RR: 0.57, 95% CI: 0.42–0.78). In conclusion, our findings support the early initiation of lifestyle intervention in women with GDM for the prevention of diabetes.     

Cognitive training on eating behaviour and weight loss: A meta‐analysis and systematic review

Cognitive deficits play a role in the development and maintenance of overeating and obesity, and cognitive training in obesity refers to a family of interventions aimed at reducing overeating and obesity by improving these cognitive deficits. In this review, we synthesize the current literature on these issues by conducting a meta‐analysis of studies investigating the effects of cognitive trainings on eating behaviour and presenting a systematic review of studies investigating the effects of cognitive trainings on weight loss. We examined 66 independent experiments that examined the effects of cognitive training aimed at reducing cognitive bias or improving executive control on eating behaviour and weight loss. Overall, inhibition training, attention bias modification training, and episodic future thinking training significantly influenced eating behaviour; however, approach/avoidance training did not significantly influence eating behaviour. Moderator analyses indicated that the effect of inhibition training on eating behaviour was moderated by training task and food novelty, the effect of approach/avoidance training was moderated by food type, and the effect of episodic future thinking training was moderated by type of episodic future thinking. Literature reviewed on cognitive training and weight loss provided preliminary support for the effects of food‐specific inhibition training on weight loss from pre‐intervention to post intervention. However, because most of the included studies focused on short‐term outcomes in normal‐weight samples, longer duration studies in clinical populations (eg, individuals with obesity) are needed to examine the generalizability of these results.     

Assessing the impact of diet,exercise and the combination of the two as a treatment for OSA: A systematic review and meta‐analysis

This study aimed to provide an updated systematic review and meta‐analysis of randomized controlled trials (RCT) investigating the effectiveness of lifestyle interventions on weight loss and the impact on the severity of obstructive sleep apnoea (OSA). A systematic search of five databases between 1980 and May 2018 was used to identify all RCT which employed a lifestyle intervention (i.e. diet‐only, exercise‐only or combination of the two) aiming to reduce the severity of OSA (assessed using the apnoea–hypopnoea index (AHI)). Random‐effects meta‐analyses followed by meta‐regression were conducted. Ten RCT involving 702 participants (Intervention group: n = 354; Control group: n = 348) were assessed in two meta‐analyses. The weighted mean difference in AHI (?8.09 events/h, 95% CI: ?11.94 to ?4.25) and body mass index (BMI, ?2.41 kg/m², 95% CI: ?4.09 to ?0.73) both significantly favoured lifestyle interventions over control arms. Subgroup analyses demonstrated that all interventions were associated with reductions in the AHI, but only the diet‐only interventions were associated with a significant reduction in BMI. No association was found between the reduction in AHI or BMI and the length of the intervention, or with baseline AHI and BMI levels. All lifestyle interventions investigated appear effective for improving OSA severity and should be an essential component of treatment for OSA. Future research should be directed towards identifying subgroups likely to reap greater treatment benefits as well as other therapeutic benefits provided by these interventions.     

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy

There is currently no pharmacotherapy for obstructive sleep apnoea (OSA) but there is no principled a priori reason why there should not be one. This review identifies a rational decision‐making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for OSA. The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their OSA pathogenesis and identify, a priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors. We then identify rational strategies to manipulate those critical predisposing factor(s), and the barriers that have to be overcome for success of any OSA pharmacotherapy. A new analysis then identifies candidate drug targets to manipulate the upper airway motor circuitry for OSA pharmacotherapy. The first conclusion is that there are two general pharmacological approaches for OSA treatment that are of the most potential benefit and are practically realistic, one being fairly intuitive but the second perhaps less so. The second conclusion is that after identifying the critical physiological obstacles to OSA pharmacotherapy, there are current therapeutic targets of high interest for future development. The final analysis provides a tabulated resource of ‘druggable’ targets that are relatively restricted to the circuitry controlling the upper airway musculature, with these candidate targets being of high priority for screening and further study. We also emphasize that a pharmacotherapy may not cure OSA per se, but may still be a useful adjunct to improve the effectiveness of, and adherence to, other treatment mainstays.     

Continuous positive airway pressure is associated with a decrease in pulmonary artery pressure in patients with obstructive sleep apnoea: A meta‐analysis

Pulmonary hypertension has been recognized as being associated with obstructive sleep apnoea (OSA). Continuous positive airway pressure (CPAP) might reduce pulmonary artery pressure in OSA patients; however, evidence from clinical studies is limited and inconsistent. This meta‐analysis aims to assess whether CPAP is associated with a decrease in pulmonary artery pressure in patients with OSA. This systematic review was performed in accordance with the Meta‐analysis of Observational Studies in Epidemiology guidelines. Published studies were identified through a search in MEDLINE, EMBASE and the Cochrane library through to May 2013. Two reviewers sorted papers and extracted data. A random‐effects model was used to combine results across studies comparing pulmonary artery pressure in OSA patients before and after CPAP treatment. Six articles with 181 patients were included in this meta‐analysis, including five before‐after studies and one matched‐control study. The meta‐analysis showed that CPAP was associated with a statistically significant reduction in pulmonary artery pressure in OSA patients (standardized mean difference ?1.34, 95% confidence interval: ?2.33 to ?0.34, P = 0.009). Although this meta‐analysis has some limitations, it indicates that CPAP is associated with a decrease in pulmonary artery pressure in patients with OSA.