Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

CONTEXT: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). OBJECTIVE: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. METHODS: Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. RESULTS: Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. CONCLUSION: In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

Benchmarking performance of an automatic polysomnography scoring system in a population with suspected sleep disorders.

Aim: The current gold standard for measuring sleep disorders is polysomnography (PSG), which is manually scored by a sleep technologist. Scoring a PSG is time-consuming and tedious, with substantial inter-rater variability. A deep-learning-based sleep analysis software module can perform autoscoring of PSG. The primary objective of the study is to validate the accuracy and reliability of the autoscoring software. The secondary objective is to measure workflow improvements in terms of time and cost via a time motion study. Methodology: The performance of an automatic PSG scoring software was benchmarked against the performance of two independent sleep technologists on PSG data collected from patients with suspected sleep disorders. The technologists at the hospital clinic and a third-party scoring company scored the PSG records independently. The scores were then compared between the technologists and the automatic scoring system. An observational study was also performed where the time taken for sleep technologists at the hospital clinic to manually score PSGs was tracked, along with the time taken by the automatic scoring software to assess for potential time savings. Results: Pearson's correlation between the manually scored apnea-hypopnea index (AHI) and the automatically scored AHI was 0.962, demonstrating a near-perfect agreement. The autoscoring system demonstrated similar results in sleep staging. The agreement between automatic staging and manual scoring was higher in terms of accuracy and Cohen's kappa than the agreement between experts. The autoscoring system took an average of 42.7 s to score each record compared with 4,243 s for manual scoring. Following a manual review of the auto scores, an average time savings of 38.6 min per PSG was observed, amounting to 0.25 full-time equivalent (FTE) savings per year. Conclusion: The findings indicate a potential for a reduction in the burden of manual scoring of PSGs by sleep technologists and may be of operational significance for sleep laboratories in the healthcare setting.

Does CPAP treat depressive symptoms in individuals with OSA? An analysis of two 12-week randomized sham CPAP-controlled trials.

BACKGROUND: Depression is common in patients with obstructive sleep apnea (OSA). Whether treating OSA with continuous positive airway pressure (CPAP) improves depressive symptoms remains inconclusive. We examined the impact of CPAP on depressive symptoms in OSA patients compared to sham CPAP. METHODS: A sub-analysis of two previous randomized sham-controlled trials was conducted. 126 male OSA patients (age = 51 ± 11 years; BMI = 32.0 ± 5.1 kg/m2; apnea hypopnea index = 42.4 ± 22.6 events/hour) were randomised either to therapeutic CPAP (n = 65) or sham CPAP (n = 61). Depressive symptoms were measured using the Depression, Anxiety and Stress Scale (DASS). The main outcome was the change in the DASS depression score (DASSD) after three months between the therapeutic and sham CPAP arms. RESULTS: The change in DASSD at three months did not differ between therapeutic and sham CPAP (mean difference: 0.5, 95% CI -3.6 to 4.6, p = 0.80). There was no significant between-group differences within the sub-groups of adherent users (device usage≥4hrs/day), or those with baseline depression (DASSD>9). In a secondary analysis of patients with baseline depression, adherent therapeutic CPAP use was associated with a greater reduction in DASSD scores compared to non-adherers (-10.0, 95% CI -18.3 to -1.8, p = 0.019). CONCLUSIONS: Overall, three months of CPAP did not significantly improve depression scores in OSA patients. Adherent use of therapeutic CPAP in patients with baseline depressive symptoms was associated with a reduction in symptom score. Future trials involving OSA patients with higher depressive symptoms will enable us to understand the complex interaction between OSA and depression.

Comparing treatment effects of a convenient vibratory positional device to CPAP in positional OSA: a crossover randomised controlled trial.

OBJECTIVES: Up to 77% of patients with obstructive sleep apnoea (OSA) have positional OSA (POSA) but traditional positional therapy (PT) methods have failed as they were poorly tolerated. New convenient vibratory PT devices have been invented but while recent studies suggest high treatment efficacy and adherence, there are no published data comparing these devices directly with continuous positive airway pressure (CPAP). Our objective is to evaluate if a convenient vibratory PT device is non-inferior to CPAP in POSA treatment. METHODS: In this crossover randomised controlled trial, we enrolled patients with POSA with significant daytime sleepiness (Epworth Sleepiness Scale (ESS)≥10). POSA diagnosis was based on: (1) total Apnoea/Hypopnoea Index (AHI)>10/hour and non-supine AHI<10/hour (2) supine AHI≥2 × non-supine AHI. Patients used their initial allocated devices (PT or CPAP) for 8 weeks before crossing to the alternative intervention after a 1 week washout. The primary aim is to measure changes in ESS between the two treatments. Secondary outcomes include sleep study parameters and patient treatment preference (ClinicalTrials.gov: NCT03125512). RESULTS: 40 patients completed the trial between April 2017 and December 2018. Difference in ESS after 8 weeks of device use (PT minus CPAP) was 2.0 (95% CI 0.68 to 3.32), exceeding our predetermined non-inferiority margin of 1.5. AHI on CPAP was lower than with PT (4.0±3.2 vs 13.0±13.8 events/hour, respectively, p=0.001), although both were lower than at baseline. Time spent supine was significantly lower with PT than CPAP (p<0.001). 60% of patients preferred CPAP, 20% preferred PT, while 20% preferred neither device. CONCLUSIONS: The non-inferiority ESS endpoint for PT compared with CPAP was not met and the results were inconclusive. Future trials with larger sample sizes or in less symptomatic patients are warranted to provide further insight into the role of these new vibratory PT devices.

Adherence to Continuous Positive Airway Pressure therapy in Singaporean patients with Obstructive Sleep Apnea.

PURPOSE: To investigate the rates of Continuous Positive Airway Pressure (CPAP) uptake and adherence amongst Singaporean patients diagnosed with Obstructive Sleep Apnea (OSA), and to evaluate factors correlated with CPAP uptake and adherence. STUDY DESIGN: Retrospective review of medical records. METHODS: Medical records were reviewed for baseline demographics, daytime sleepiness, presence of nasal symptoms and OSA severity, initial treatment choice, the rate of CPAP treatment uptake and CPAP adherence at 1 and 12 months. RESULTS: 2160 patients were diagnosed with OSA within the 5-year period (2011-2015). 463 (21.4%) had mild OSA, 583 (27.0%) had moderate OSA and 1114 (51.6%) had severe OSA. For initial therapy, 751 (34.8%) patients opted for a 1-month CPAP trial, 288 (13.3%) patients chose surgery upfront, 291 (13.5%) patients chose adjunctive treatments (weight loss, positional therapy, dental appliance, intranasal steroid spray for allergic rhinitis) and 830 (38.4%) patients rejected all forms of treatment. 337 out of 751 patients (44.9%) were adherent to CPAP therapy during the 1 month trial. 381 out of 751 (50.7%) patients took up CPAP therapy following the trial period, of which 299 out of 381 (78.5%) patients were adherent to CPAP therapy at 1 year. CPAP adherence during the 1-month trial was a predictor for eventual CPAP treatment uptake and CPAP adherence at 1 year (p < 0.001). Age (p < 0.001), BMI (p < 0.001) and normal ESS (p = 0.01) were predictors of treatment rejection. 24 patients underwent upper airway surgery during their first year of using CPAP. 21 out of the 24 patients (87.5%) were adherent to CPAP at 1 year after undergoing surgery. These patients had a higher rate of CPAP adherence compared to the overall cohort (87.5% versus 78.5%), but this was not statistically significant (p > 0.05). CONCLUSION: Singaporean patients who accept CPAP therapy after an initial 1-month CPAP trial will generally be adherent to CPAP therapy. Initial patterns of CPAP usage are predictive of long term CPAP adherence. However, there is a high rate of CPAP treatment rejection both at the time of diagnosis and after the CPAP trial. Upper airway surgery in selected patients may improve CPAP adherence.

The relationship between pulmonary hypertension and obstructive sleep apnea.

PURPOSE OF REVIEW: Although obstructive sleep apnea (OSA)-associated pulmonary hypertension is not uncommon and carries a worse prognosis if left untreated, it is less well recognized by clinicians. This review provides information on prevalence, pathophysiology, clinical presentation, treatment, and prognosis of pulmonary hypertension in OSA. RECENT FINDINGS: The prevalence of pulmonary hypertension in OSA ranges from 17 to 53%. The underlying pathophysiology is complex and yet to be fully understood. Continuous positive airway pressure has been proven to be efficacious in the treatment of OSA-associated pulmonary hypertension. SUMMARY: There is still lack of research in this field. We look forward to more well designed studies to help us understand this disease entity better.

Obstructive sleep apnoea and Type 2 diabetes mellitus: are they connected?

Obstructive sleep apnoea (OSA), a sleep-related breathing condition, is diagnosed based on a patient's apnoea-hypopnea index from a sleep study, and the presence or absence of symptoms. Diabetes mellitus (DM) and OSA share a significant common risk factor, obesity, with all three conditions contributing to the risk of developing cardiovascular diseases. The pathophysiological links between OSA and DM are still unclear, but intermittent hypoxia may be an important mechanism. More awareness of the possible link between OSA and DM is needed, given their increasing prevalence locally and worldwide. Continuous positive airway pressure is the standard treatment for OSA, while weight loss through dietary and lifestyle modifications is important to holistically manage patients with either condition. There is currently insufficient evidence to support the benefits of screening every diabetic patient for OSA. However, diabetic patients with symptoms suggestive of OSA should be referred to a sleep specialist for further evaluation.

Secondary hypertension in adults.

Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately.

A rare but potentially lethal complication of dengue.

Severe rhabdomyolysis is an uncommon but potentially fatal complication of dengue fever that is not well characterised and may be underreported. With the resurgence and continued rise of dengue cases worldwide, physicians must be aware of the less common but serious complications of dengue. Here, we report a patient who presented with severe rhabdomyolysis secondary to dengue fever with a serum creatine kinase of 742 900 U/L.