Improved survival following ward-based non-invasive pressure support for severe hypoxia in a cohort of frail patients with COVID-19: retrospective analysis from a UK teaching hospital.

Since the outbreak of COVID-19 in China in December 2019, a pandemic has rapidly developed on a scale that has overwhelmed health services in a number of countries. COVID-19 has the potential to lead to severe hypoxia; this is usually the cause of death if it occurs. In a substantial number of patients, adequate arterial oxygenation cannot be achieved with supplementary oxygen therapy alone. To date, there has been no clear guideline endorsement of ward-based non-invasive pressure support (NIPS) for severely hypoxic patients who are deemed unlikely to benefit from invasive ventilation. We established a ward-based NIPS service for COVID-19 PCR-positive patients, with severe hypoxia, and in whom escalation to critical care for invasive ventilation was not deemed appropriate. A retrospective analysis of survival in these patients was undertaken. Twenty-eight patients were included. Ward-based NIPS for severe hypoxia was associated with a 50% survival in this cohort. This compares favourably with Intensive Care National Audit and Research Centre survival data following invasive ventilation in a less frail, less comorbid and younger population. These results suggest that ward-based NIPS should be considered as a treatment option in an integrated escalation strategy in all units managing respiratory failure secondary to COVID-19.

Continuous positive airway pressure effect on visual acuity in patients with type 2 diabetes and obstructive sleep apnoea: a multicentre randomised controlled trial.

We sought to establish whether continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) in people with type 2 diabetes and diabetic macular oedema (DMO) improved visual acuity.We randomly assigned 131 eligible patients aged 30-85 years from 23 UK centres with significant DMO causing visual impairment (LogMAR letters identified ≥39 and ≤78, score 0.92-0.14) plus severe OSA on screening to either usual ophthalmology care (n=67) or usual ophthalmology care plus CPAP (n=64) for 12 months.Mean age of participants was 64 years, 73% male, mean body mass index 35.0 kg·m- 2 Mean 4% oxygen desaturation index was 36 events·h-1 There was no significant difference in the visual acuity at 12 months between the CPAP group and the control group (mean LogMAR 0.33 (95% CI 0.29-0.37) versus 0.31 (95% CI 0.27-0.35); p=0.39), and no significant correlation between change in LogMAR and average CPAP use. The median±sd (range) daily CPAP use was 3.33±2.25 (0-7.93) h at 3 months, 3.19±2.54 (0-8.07) h at 6 months and 3.21±2.70 (0-7.98) h at 12 months.CPAP therapy for OSA did not improve visual acuity in people with type 2 diabetes and DMO compared with usual care alone over 12 months.

Obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. While OSA is a disorder primarily of the upper airway during sleep, its pathophysiological impact on other body systems is increasingly recognised. There has been interest in the prevalence of OSA in different ophthalmic conditions and possible causation has been postulated. As OSA is common, it can be expected that people with co-existent OSA will be found in any ophthalmic disease population studied. To determine with confidence the significance of finding patients with OSA in a particular cohort requires a well matched control group, ideally matched for age, obesity, gender and co-morbidities. Only if one can say with certainty that the prevalence of OSA is higher in a group with a particular co-existent ophthalmic disease can we begin to speculate about possible mechanisms for the overlap in these conditions. Possible mechanisms for how OSA might affect the eye are discussed in this review. The current literature is reviewed with respect to diabetic retinopathy, glaucoma, floppy eyelid syndrome, non-arteritic ischaemic optic neuropathy, keratoconus and AMD. Associations with OSA have been found, but robust prospective studies using multi-channel sleep studies to diagnose OSA are lacking. Gaps remain in the evidence and in our knowledge. It is hoped that this review will highlight the need for ophthalmologists to consider OSA in their patients. It also makes recommendations for future research, especially to consider whether therapies for OSA can also be effective for ophthalmic disorders.

A 4-week wait 'fast-track' sleep service is effective at establishing vocational drivers on continuous positive airway pressure.

We sought to establish whether an expedited or 'fast-track' NHS service to diagnose obstructive sleep apnoea (OSA) and establish vocational drivers on continuous positive airway pressure (CPAP) within 4 weeks of referral was possible. This model is recommended by the OSA Partnership Group. In total, 55 vocational drivers were referred to two sleep services. Assessment showed 73% had moderate or severe OSA on sleep study. Of those commenced on CPAP, review was a mean of 15 days after initiation (range 3-62 days). Median time from referral (or first clinic visit) to review on CPAP was 32 days, showing a 'fast-track' pathway is deliverable.

Sleepiness and Sleep-related Breathing Disorders in Myotonic Dystrophy and Responses to Treatment: A Prospective Cohort Study.

OBJECTIVE: We conducted prospective assessments in people with myotonic dystrophy type 1 (DM1) with daytime sleepiness, provided targeted therapies and assessed response. METHODS: Patients had overnight sleep assessments. Treatment with continuous positive airway pressure (CPAP) for OSA, non-invasive ventilation (NIV) for respiratory failure, modafinil for excessive daytime sleepiness were commenced. RESULTS: 120 people were studied: mean age 46.9 years (SD 13.2, range 18-74), body mass index 27.9 kg/m2 (7.2, 16-53), Epworth Sleepiness Score (ESS) 13.1 (4.7, 2-24). Twenty one people (18% of group) had OSA: mean age 49.6, BMI 31.1, ESS 14.3, ODI 22, pO2 11.3, pCO2 5.4. All were offered CPAP; seven continued with benefit but 14 had intolerance or no benefit. Thirty-three people (27%) had respiratory failure and abnormal sleep study: mean age 51.5, BMI 31.3, ESS 13.9, ODI 22.9, pO2 8.7, pCO2 6.8. All were offered NIV; 12 continued with benefit but 18 had intolerance or no benefit, 1 died and 2 declined commencement. Thirty-six people (30%) had predominantly sleepiness: mean age 44.8, BMI 24.6, ESS 14.1, ODI 9.2, pO2 11.7, pCO2 5.4. All were offered modafinil; 12 continued this with benefit but 10 had intolerance or no benefit, one was unkeen to start, 11 did not attend further clinic and two had other sleep disorders. Comparing means of treatment responders to non-responders showed no significant difference in any variable, except ESS: 15.9 vs.11.9 respectively, p < 0.0001. CONCLUSIONS: Causes of sleepiness are variable in DM1, but include obstructive sleep apnoea, respiratory failure and sleepiness with a normal sleep study; 29% of this studied cohort benefited from targeted sleep therapies.

Eye disorders associated with obstructive sleep apnoea.

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. Public awareness is also growing. Although OSA is a disorder primarily of the upper airway during sleep, its physiological impact on other parts of the body is now well recognized. There is increasing interest in the association of OSA with various eye disorders. Work in this field has been directed predominantly to OSA prevalence and association studies, but some authors have tried to elucidate the effect of OSA therapies on eye diseases, including continuous positive airway pressure, upper airway surgery or bariatric surgery. This review discusses the publications in this area from the past year. RECENT FINDINGS: The key ocular disorders featured in the studies and meta-analayses include glaucoma, floppy eyelid syndrome, nonarteritic ischaemic optic neuropathy, keratoconus, age-related macular degeneration and diabetic retinopathy. Associations with OSA were found with all these conditions, but aspects of the studies still leave gaps in our knowledge. SUMMARY: This review highlights the need for ophthalmologists to consider OSA in their patients and also makes recommendations for future research studies, especially whether therapies for OSA can be effective for ocular disorders also.

Serum urate levels are unchanged with continuous positive airway pressure therapy for obstructive sleep apnea: a randomized controlled trial.

OBJECTIVE: Hyperuricemia is associated with the presence and severity of obstructive sleep apnea (OSA). Previous work has shown that treatment of OSA with continuous positive airway pressure (CPAP) therapy reduces urinary uric acid excretion and serum urate, but there has been no previous randomized controlled investigation on the effects of CPAP therapy on serum urate; we aimed to assess this association. METHODS: Serum urate was measured in samples from participants of a previously published randomized controlled trial. Samples were taken at baseline and after 3months from men with known type 2 diabetes mellitus (T2DM) and newly diagnosed OSA, randomized to receive either therapeutic (n=19) or placebo (n=19) CPAP for 3months. RESULTS: Both groups were well matched at baseline, with no significant difference in age, body mass index (BMI), glycosylated hemoglobin (HbA1c), or oxygen desaturation index (ODI). There was no significant difference in therapeutic or placebo CPAP usage. There was no significant difference in urate levels between groups at baseline (362µmol/L [standard deviation {SD}, 96] vs 413µmol/L [SD, 91] [reference range, 110-428µmol/L]) or at 3months. Baseline urate did not correlate with ODI, BMI, or HbA1c. The mean change in urate at 3months did not significantly differ between treatment groups (-7.6µmol/L [SD, 35.9] vs -6.2µmol/L [SD, 46.2]) (P=.9; [95% confidence interval, -28.7 to +25.9]). CONCLUSION: Our randomized controlled trial has shown no significant reduction in serum urate following 3months treatment with therapeutic or placebo CPAP.

High prevalence of sleep disordered breathing in patients with diabetic macular edema.

BACKGROUND: Diabetic retinopathy is more common and severe in patients with sleep disordered breathing (SDB). This study aimed to establish whether this is also true for patients with diabetic clinically significant macular edema (CSME). It is hypothesized that SDB, through intermittent hypoxia and blood pressure oscillations, might provoke worsening of CSME. METHODS: Patients with CSME had a home sleep study (ApneaLink; ResMed) to identify SDB. These results were compared with relevant control populations. Macular thickness was measured using optical coherence tomography, and retinal photographs were graded to assess the severity of retinopathy. RESULTS: Eighty of 195 patients (40 men) consented, with average age of 64.7 (11.7) years, neck circumference of 40.4 (5.4) cm, body mass index of 30.2 (6.2) kg/m2, glycosylated hemoglobin (HbA1c) 7.8% (1.4%) [62 (8.0) mmol/mol], and Epworth sleepiness scale of 7.4 (4.8). Overall, 54% had an oxygen desaturation index ≥ 10, and 31% had an apnea-hypopnea index ≥ 15. This SDB prevalence is probably higher than would be expected from the available matched control data. Those with SDB were not sleepier, but they were older and more obese. No significant relationship was identified between the degree of macular thickness and the severity of SDB. CONCLUSION: Individuals with CSME have a high prevalence of SDB. Sleep disordered breathing may contribute to the pathophysiology of CSME, but the mechanism remains unclear. Given the high prevalence, retinal specialists should perhaps consider a diagnosis of SDB in patients with CSME.

Is obstructive sleep apnea a risk factor for diabetes?

Obstructive sleep apnea (OSA) and type 2 diabetes are both closely related to obesity and their prevalence is increasing due to the rising average body weight in Western countries. The findings of epidemiological studies have implicated that OSA increases the risk for cardiovascular disease, and metabolic disturbances, such as insulin resistance, may link OSA to vascular morbidity. A number of observational clinical studies have evaluated the relationship between OSA and insulin resistance, suggesting an independent association. However, the confounding effect of obesity complicates the establishment of a causal relationship between OSA and insulin resistance. Potential mechanisms that may underpin this relationship were evaluated in animal and human experimental studies and include intermittent hypoxia, arousals from sleep with concomitant sympathetic activation and sleep fragmentation. Currently only three randomized controlled trials investigating the effects of OSA on insulin resistance have been published. In these trials OSA patients were randomly assigned to treatment with continuous positive airway pressure (CPAP) or subtherapeutic CPAP and treatment effects on various measures of insulin resistance were examined. In two of these trials there was no effect of CPAP on glucose metabolism and in one trial a small beneficial effect of CPAP was observed. Further carefully conducted clinical studies and randomized controlled interventional CPAP trials are needed to determine the extent to which OSA is a risk factor for diabetes and its effect on glucose metabolism.

The effect of continuous positive airway pressure treatment on physical activity in patients with obstructive sleep apnoea: A randomised controlled trial.

BACKGROUND: Continuous positive airway pressure (CPAP) improves daytime sleepiness in patients with obstructive sleep apnoea (OSA). The effect of CPAP on physical activity is unclear. We hypothesized that activity would increase after CPAP treatment. METHODS: A double blind, parallel, randomised, controlled trial using therapeutic and placebo CPAP was performed in men with newly diagnosed OSA (more than 10>4% SaO(2) dips/hour and Epworth Sleepiness Score [ESS] 9). Activity was measured by wrist actigraphy before and after three months of CPAP therapy. RESULTS: Thirty-six men completed 1 week of continuous actigraphy before and after therapeutic CPAP (n=16) or placebo CPAP (n=20). The two groups were well-matched at baseline, with no significant differences in mean age, body mass index, ESS and SaO(2) dips/hour. Mean (SD) ESS and modified maintenance of wakefulness test (OSLER) improved significantly after CPAP. ESS change in the therapeutic group was -6.1 (4.4), compared to placebo, -2.8 (5.0); difference between groups p=0.04; OSLER (minutes), therapeutic +10.4 (14.4), placebo -5.0 (12.0), p=0.003. There was no significant difference between groups in mean hourly activity levels for the seven days at baseline; activity levels did not significantly change in either group after CPAP [daytime activity (arbitrary units): therapeutic -13.9 (93.1) vs. placebo +8.3 (62.9), p=0.4]. There was no correlation between change in activity and CPAP use. CONCLUSION: Activity does not increase after CPAP in men with OSA, despite improvements in daytime sleepiness. The reasons for this are not clear, but may be due to longstanding, habitual patterns of activity.

Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes.

BACKGROUND: The effects of continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) on insulin resistance are not clear. Trials have found conflicting results and no appropriate control groups have been used. METHODS: Forty-two men with known type 2 diabetes and newly diagnosed OSA (>10 dips/h in oxygen saturation of >4%) were randomised to receive therapeutic (n = 20) or placebo CPAP (n = 22) for 3 months. Baseline tests were performed and repeated after 3 months. The study was double blind. RESULTS: Results are expressed as mean (SD). CPAP improved the Epworth sleepiness score significantly more in the therapeutic group than in the placebo group (-6.6 (4.5) vs -2.6 (4.9), p = 0.01). The maintenance of wakefulness test improved significantly in the therapeutic group but not in the placebo group (+10.6 (13.9) vs -4.7 (11.8) min, p = 0.001). Glycaemic control and insulin resistance did not significantly change in either the therapeutic or placebo groups: HbA1c (-0.02 (1.5) vs +0.1 (0.7), p = 0.7, 95% CI -0.6% to +0.9%), euglycaemic clamp (M/I: +1.7 (14.1) vs -5.7 (14.8), p = 0.2, 95% CI -1.8 to +0.3 l/kg/min(1000)), HOMA-%S (-1.5 (2.3) vs -1.1 (1.8), p = 0.2, 95% CI -0.3% to +0.08%) and adiponectin (-1.1 (1.2) vs -1.1 (1.3), p = 0.2, 95% CI -0.7 to +0.6 microg/ml). Body mass index, bioimpedance and anthropometric measurements were unchanged. Hours of CPAP use per night were 3.6 (2.8) in the treatment group and 3.3 (3.0) in the placebo group (p = 0.8). There was no correlation between CPAP use and the measures of glycaemic control or insulin resistance. CONCLUSION: Therapeutic CPAP does not significantly improve measures of glycaemic control or insulin resistance in men with type 2 diabetes and OSA.

Management of malignant pleural mesothelioma.

Malignant mesothelioma is increasing in incidence globally and has no known cure. Its unique clinical feature of local infiltration along tissue planes makes it a difficult neoplasm to manage. There have been few randomized controlled trials regarding treatment options, although these have increased in recent years, and results are eagerly awaited. This article summarizes important advances in the management of mesothelioma, especially diagnostic and therapeutic aspects.

Needle-track metastases and prophylactic radiotherapy for mesothelioma.

BACKGROUND: Mesothelioma invades the tracts made by chest instrumentation. Prophylactic radiotherapy is effective at preventing malignant seeding at these sites. METHODS: We assessed the use and effectiveness of radiotherapy at our centre in 39 of the 40 patients identified with mesothelioma between January 2000 and September 2003. RESULTS: Thirty-seven (95%) patients received radiotherapy to their chest instrumentation site between 6 and 42 days (median 26 days) following the diagnosis of mesothelioma. The radiotherapy field size varied, from 4 cm square to 14 x 10.5 cm. The radiotherapy was given as 21 Gy in 3 fractions over 1 week. In 3 patients (8%), there was already tumour invasion of the skin at the time of radiotherapy. In 2 other patients (5%), there was tumour recurrence following radiotherapy; in both this was at the edge of the previous radiotherapy fields. Further treatment was administered to an adjacent field in both. One patient with an indwelling pleural catheter developed tumour growth at the catheter insertion site. This was treated successfully with radiotherapy, with no catheter damage. CONCLUSIONS: Prompt radiotherapy referral and radiotherapy field selection is important to maximise the effect of radiotherapy given to prevent chest wall tumour growth. There was no tumour growth in areas that were treated with radiotherapy. Further chest interventions outside the radiotherapy field should be followed with further radiotherapy.

Pleurodesis for malignant pleural effusions: current controversies and variations in practices.

PURPOSE OF REVIEW: Malignant pleural effusions are common, and pleurodesis remains the best method to control re-accumulation of the pleural fluid. There are few randomized controlled trials studying the optimal management of malignant pleural effusions. A recent international survey of pleurodesis practice has highlighted variations in how pleurodesis is performed worldwide. Future research should target these areas of variation to determine the best practice protocols. RECENT FINDINGS: The selection of pleurodesing agents remains controversial. Talc is more effective, but is associated with more adverse effects. Talc pleurodesis is followed by systemic and pulmonary inflammation. This is probably related to systemic embolization of talc following its intrapleural administration, though there are other potential causes that may also play a role. SUMMARY: The practice of pleurodesis varies considerably among individual pulmonologists and among different countries, in most technical aspects. This review serves to highlight some of these variations in practice, as well as reviewing the current literature on pleurodesis practice.