Population-based epidemiologic studies have uncovered the high prevalence and wide severity spectrum of undiagnosed obstructive sleep apnea, and have consistently found that even mild obstructive sleep apnea is associated with significant morbidity. Evidence from methodologically strong cohort studies indicates that undiagnosed obstructive sleep apnea, with or without symptoms, is independently associated with increased likelihood of hypertension, cardiovascular disease, stroke, daytime sleepiness, motor vehicle accidents, and diminished quality of life. Strategies to decrease the high prevalence and associated morbidity of obstructive sleep apnea are critically needed. The reduction or elimination of risk factors through public health initiatives with clinical support holds promise. Potentially modifiable risk factors considered in this review include overweight and obesity, alcohol, smoking, nasal congestion, and estrogen depletion in menopause. Data suggest that obstructive sleep apnea is associated with all these factors, but at present the only intervention strategy supported with adequate evidence is weight loss. A focus on weight control is especially important given the expanding epidemic of overweight and obesity in the United States. Primary care providers will be central to clinical approaches for addressing the burden and the development of cost-effective case-finding strategies and feasible treatment for mild obstructive sleep apnea warrants high priority.

Epidemiology of obstructive sleep apnea: a population health perspective.

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

Systematic review of levodopa dose equivalency reporting in Parkinson's disease

https://www.ecnp.eu/~/media/Files/ecnp/communication/reports/ECNP%20EBC%20Report.pdf

The size and burden of mental disorders and other disorders of the brain in Europe 2010

Measuring Health: A Guide to Rating Scales and Questionnaires

The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(06)70373-8.pdf

Non-motor symptoms of Parkinson's disease: diagnosis and management

Phasic activity and the importance of irregular breathing.

Catathrenia is an uncommon and poorly understood disorder, characterized by groaning during sleep occurring in tandem with prolonged expiration. Its classification, pathogenesis and clinical relevance remain debated, substantially due to the limited number of cases reported to date. We report a series of consecutive cases of catathrenia, their clinical and PSG characteristics, and their subsequent management. Consecutive patients with catathrenia who had undergone full PSG in our institution over a 5-and-half-year period were included. Catathrenia events (CEs) were examined in clusters, formulating catathrenia periods (CPs). The relationships between CPs, sleep stage distribution, EEG arousals, and other sleep parameters were assessed, along with the clinical presentation and management of catathrenic patients. A total of 427 CPs were identified in 38 patients, 81% arising from REM sleep. EEG arousals preceded or coincided with the onset of 84% of CPs, which were of longer duration than those not associated with an arousal (57.3±56.8 vs 32.2±29.4 sec, p In the largest series of catathrenia patients reported to date, we found that this rare disorder is characterized by a distinct breathing pattern, and arises predominantly from REM sleep, with arousals almost uniformly preceding or coinciding with the onset of catathrenia periods.

Catathrenia as a REM predominant disorder of arousal

Background Obesity-related SDB requiring domiciliary non-invasive ventilation (NIV) can present as (1) eucapnic obstructive sleep apnoea (OSA) (2) hypercapnic OSA (P a CO 2 >6 kPa) (3) hypercapnic OSA with obesity hypoventilation syndrome (OHS) and (4) lone OHS. We have adopted the term obesity-related respiratory failure (ORRF) to group these differing conditions. The aim of this study was to determine the clinical features prevalent in each of these conditions in order to guide respiratory management. Method Data from patients initiated on domiciliary NIV at a tertiary referral unit, between August 2005 and December 2009, were obtained from a purpose-designed discharge summary database. Patients were categorised into four groups, as described above. Comparative analyses were performed between (1) eucapnic OSA and the hypercapnic groups (2) hypercapnic OSA and a group combining the OSA with OHS and the lone OHS groups (OSA & OHS and lone OHS) and (3) eucapnic and hypercapnic OSA. Logistic regression analysis was performed to determine factors associated with hypercapnia. Results 163 patients were included in the analyses. Group mean (SD) age 54.3±14.2 years, weight 134.4±33.1 kg, body mass index (BMI) 48.4±2.5 kg/m 2 and Epworth sleepiness (ESS) score 14.8±5.8. Results are shown in Abstract S67 Table 1. The hypercapnic groups demonstrated a higher prevalence of diabetes. In addition, hypercapnic patients were overall, compared with eucapnic patients, more hypoxic with greater lung restriction, despite a non-significant increase in BMI in the hypercapnic OSA group. Compared with the hypercapnic OSA group, the combined OSA and OHS and lone OHS group had a higher BMI, ESS and greater hypercapnia. However, logistic regression analysis failed to demonstrate any factors that predicted hypercapnia. Conclusion Demographic, anthropometric, spirometric and clinical features allow the different ORRF conditions to be distinguished. BMI, daytime symptoms and degree of chronic respiratory failure distinguished between hypercapnic OSA from obesity-related hypoventilation. Although we hypothesise that ORRF is a disease spectrum, from eucapnic OSA progressing to hypercapnic OSA to OSA with OHS, we were unable to identify factors that predicted hypercapnia. From these data, we propose that more detailed physiological assessment, including neural respiratory drive and pulmonary mechanics, is required.

https://thorax.bmj.com/content/thoraxjnl/65/Suppl_4/A32.1.full.pdf

S67 Phenotypic differences between obese patients with eucapnic and hypercapnic sleep-disordered breathing (SDB)

Introduction There are few effective therapies available for the long-term management of the cardiac and renal sequelae of SCD. Identifying reversible factors, which exacerbate disease severity, would facilitate development of new therapies or novel applications of established treatments. Nocturnal hypoxia (NH) merits investigation as a disease modulating factor as it is established that hypoxia promotes polymerisation of sickle haemoglobin and this is reversible with oxygen therapy (Noguchi et al, 1993). Although NH is common in children with SCD and is associated with poor outcome, similar data for adults with SCD are lacking. This is the first study to determine the prevalence of OSA and NH and quantify the severity of NH in adults with SCD. In addition, we investigated the correlation between the degree of NH and organ dysfunction. Method Patients attending SCD clinic had an Epworth sleepiness score performed. Patients with either an ESS ≥10 or symptoms suggestive of SDB were offered nocturnal oximetry. Nocturnal oximetry findings were objectively scored and compared with the detailed clinical datasets collected at regular clinic attendances. OSA was defined as 4% oxygen desaturation index (4% ODI) of >10 events/h and NH was defined as >30% total sleep time (TST) with SpO2 Results 93 patients were screened. 34 had ESS ≥10 or clinical symptoms suggestive of SDB. 22 underwent nocturnal oximetry; mean ESS 12±4, clinic SpO2 96±4%, 4% ODI 8±6 events/h, nocturnal SpO2 91±4%, %TST SpO2 Conclusion This small pilot study showed that OSA and NH had a prevalence of 59% in symptomatic adult SCD patients. These data have demonstrated a correlation between the severity of nocturnal hypoxia and pulmonary hypertension, renal impairment and priapism. These observations have not previously been reported. The strength of these correlations could suggest a causal relationship, although this needs to be confirmed in a larger prospective trial. Future studies should investigate the relationship between OSA, nocturnal hypoxia and organ dysfunction and need to be focussed on interventions such as nocturnal oxygen and continuous positive airway pressure.

https://thorax.bmj.com/content/thoraxjnl/65/Suppl_4/A11.1.full.pdf

S17 A pilot study of the prevalence of sleep disordered breathing (SDB) and nocturnal hypoxia in symptomatic adults with Sickle Cell Disease (SCD) and its relationship with disease severity

https://www.medicinejournal.co.uk/article/S1357-3039(16)30013-5/pdf

Adrian J. Williams

Papers

Phasic activity and the importance of irregular breathing.

Catathrenia as a REM predominant disorder of arousal

S67 Phenotypic differences between obese patients with eucapnic and hypercapnic sleep-disordered breathing (SDB)

S17 A pilot study of the prevalence of sleep disordered breathing (SDB) and nocturnal hypoxia in symptomatic adults with Sickle Cell Disease (SCD) and its relationship with disease severity

The sleepy patient