Publications by authors named "John M Shneerson"

40 Publications

'Distant socializing,' not 'social distancing' as a public health strategy for COVID-19.

Pathog Glob Health 2021 09 30;115(6):357-364. Epub 2021 May 30.

Centre for Depression and Suicide Studies, St. Michael's Hospital, Toronto, Canada.

Social distancing, also referred to as physical distancing, means creating a safe distance of at least two meters (six feet) between yourself and others. This is a term popularized during the COVID-19 pandemic, as it is one of the most important measures to prevent the spread of this virus. However, the term 'social distancing' can be misleading, as it may imply that individuals should stop socializing. However, socializing in a safe context (i.e. over the phone, video-chat, etc.) is especially important during this time of crisis. Therefore, in this narrative review, we suggest the term 'distant socializing' as more apt expression, to promote physical distancing measures while also highlighting the importance of maintaining social bonds. Further, articles discussing the practice, implementation, measurement, and mental health effects of physical distancing are reviewed. Physical distancing is associated with psychiatric symptoms (such as anxiety and depression), suicidal ideation, and domestic violence. Further, unemployment and job insecurity have significantly increased during COVID-19, which may exacerbate these negative mental health effects. Governments, medical institutions, and public health bodies should therefore consider increasing mental health resources both during and after the pandemic, with a specific focus on frontline workers, COVID-19 survivors, and marginalized communities.
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http://dx.doi.org/10.1080/20477724.2021.1930713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592617PMC
September 2021

Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England.

Sleep 2016 05 1;39(5):1051-7. Epub 2016 May 1.

Consultant Epidemiologist, Public Health England, London, UK.

Study Objectives: An increased risk of narcolepsy has been observed in children following ASO3-adjuvanted pandemic A/H1N1 2009 (Pandemrix) vaccine. We investigated whether this risk extends to adults in England.

Methods: Six adult sleep centers in England were visited between November 2012 and February 2014 and vaccination/clinical histories obtained from general practitioners. Suspected narcolepsy cases aged older than 17 y were selected. The risk of narcolepsy following Pandemrix was calculated using cases diagnosed by the time of the center visits and those with a diagnosis by November 30, 2011 after which there was increased awareness of the risk in children. The odds of vaccination in cases and in matched population data were compared using a case-coverage design.

Results: Of 1,446 possible cases identified, most had onset before 2009 or were clearly not narcolepsy. Of the 60 remaining cases, 20 were excluded after expert review, leaving 40 cases with narcolepsy; 5 had received Pandemrix between 3 and 18 mo before onset. All the vaccinated cases had cataplexy, two received a diagnosis by November 2011 and two were aged 40 y or older. The odds ratio for vaccination in cases compared to the population was 4.24 (95% confidence interval 1.45-12.38) using all cases and 9.06 (1.90-43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses.

Conclusions: We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design.
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http://dx.doi.org/10.5665/sleep.5752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835303PMC
May 2016

Sleep deficits but no metabolic deficits in premanifest Huntington's disease.

Ann Neurol 2015 Oct 21;78(4):630-48. Epub 2015 Aug 21.

John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Objective: Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage.

Methods: We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age- and sex-matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x-ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain.

Results: Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4-7Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations.

Interpretation: The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology.
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http://dx.doi.org/10.1002/ana.24495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832311PMC
October 2015

Pre-flight assessment in patients with obesity hypoventilation syndrome.

Respirology 2014 Nov 23;19(8):1229-32. Epub 2014 Jul 23.

Department of Respiratory Medicine, Southend University Hospital NHS Foundation Trust, UK.

Background And Objective: Reduced atmospheric pressure during air travel can cause significant hypoxaemia in some patients with respiratory disease. Our aims were to investigate the degree of hypoxaemia in patients with obesity hypoventilation syndrome (OHS) during hypoxic challenge test (HCT), and to identify any predictors of a positive HCT.

Methods: Thirteen patients underwent assessment, including HCT, lung function and incremental shuttle walk test. All had OHS well controlled with long-term nocturnal non-invasive ventilation (NIV). Patients with chronic obstructive pulmonary disease were excluded. A positive HCT was defined according to the British Thoracic Society (BTS) recommendation as arterial oxygen tension (PaO₂) <6.6 kPa and/or oxygen saturation <85%.

Results: Mean age was 57 (± 11) years. Mean body mass index was 51.7 (± 12) kg/m(2) . Mean baseline PaO₂ and arterial carbon dioxide tension (PaCO₂) were 10.2 (9.5-11.3) kPa and 5.2 (3.7-6.8) kPa, respectively. Seven patients (54%) had a positive HCT. The correlation between baseline PaO₂ and PaO₂ at the end of the HCT was not statistically significant (r = 0.433, P = 0.184). A negative correlation was observed between baseline PaCO₂ and PaO₂ at the end of the HCT (r = -0.793, P = 0.004). A positive correlation was observed between the distance walked and the PaO₂ at the end of the HCT (r = 0.608, P = 0.047).

Conclusions: OHS is a risk factor for severe hypoxaemia during air travel even if the ventilatory failure is well controlled. An HCT before air travel is advisable in all OHS patients. Those with positive HCT may use NIV or have oxygen on-board as per BTS recommendation.
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http://dx.doi.org/10.1111/resp.12353DOI Listing
November 2014

Sleep and circadian rhythm regulation in early Parkinson disease.

JAMA Neurol 2014 May;71(5):589-595

John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, England (Breen, Vuono, Fisher, Barker); Respiratory and Sleep Support Centre, Papworth Hospital, Cambridge, England (Nawarathna, Shneerson); Institute of Metabolic Science, University of Cambridge, Cambridge, England (Reddy).

Importance: Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood.

Objective: To define the sleep and circadian phenotype of patients with early-stage Parkinson disease.

Design, Setting, And Participants: Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15).

Main Outcomes And Measures: Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erbα).

Results: Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls.

Conclusions And Relevance: Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms.
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http://dx.doi.org/10.1001/jamaneurol.2014.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119609PMC
May 2014

Narcolepsy Associated with Duane's Syndrome.

Clin Med Insights Case Rep 2014 Jan 8;7:1-2. Epub 2014 Jan 8.

Director of Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, England.

The best characterised disorder of REM sleep, narcolepsy has never previously been associated with Duane's syndrome, in which there is developmental failure of the abducens nerve and its nucleus. The major brain stem nuclei responsible for REM sleep generation are situated in the pons in close proximity to the abducens nerve nucleus. We report the novel combination of Duane's syndrome and narcolepsy, providing new insight into the pathogenesis of narcolepsy.
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http://dx.doi.org/10.4137/CCRep.S8229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891778PMC
January 2014

A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy.

J Clin Endocrinol Metab 2013 Mar 7;98(3):1040-50. Epub 2013 Feb 7.

Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Box 289, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom.

Context: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management.

Objective: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort.

Study Design: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy.

Results: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 μg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged.

Conclusions: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.
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http://dx.doi.org/10.1210/jc.2012-3072DOI Listing
March 2013

Who will benefit from tracheostomy ventilation in motor neuron disease?

Authors:
John M Shneerson

Thorax 2011 Nov 3;66(11):932-3. Epub 2011 Aug 3.

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http://dx.doi.org/10.1136/thoraxjnl-2011-200728DOI Listing
November 2011

High pain frequency in narcolepsy with cataplexy.

Sleep Med 2011 Jun 12;12(6):572-7. Epub 2011 May 12.

Department of Neurology, Hôpital Gui de Chauliac, CHU Montpellier, National Reference Network for Orphan Diseases (Narcolepsy), Montpellier, France.

Background: Narcolepsy with cataplexy (NC) is caused by the loss of hypocretin neurons. Recent studies highlighted the roles for hypocretins in the modulation of nociceptive transmission. The aims of the present multicenter case-control study were to look at the frequency of pain in NC and to study the determinants and impact of pain on narcolepsy symptoms and quality of life (QoL).

Methods: Sixty-seven adult patients with NC, together with their physician, partner/friend, and sex- and age-matched normal controls underwent a face-to-face interview and completed questionnaires on the presence and frequency of pain, narcolepsy symptoms and QoL (Short-Form 36-item score, Functional Outcomes of Sleep Questionnaire, Medical Outcomes Study, Fatigue Severity Scale, and Beck Depression Inventory).

Results: One-third (32.8%) of NC patients experienced pain at least monthly, with a significantly higher frequency and impact than controls (17.9%) and independent of the patients' narcolepsy medication. The reporting of pain was well matched between patients and partners/friends but significant differences were observed between patients and physicians, with physicians significantly underestimating its frequency and impact. The location of chronic pain varies within subjects with differences between NC and controls. We pinpointed that sleep quantity and depression were determinants for pain, and chronic pain had significant impact on sleep quantity, depression and QoL in NC.

Conclusion: We report, for the first time, evidence that chronic pain is significantly more common and disabling in NC compared to the general population. The findings call for improved attention to assessment and treatment of pain in the follow-up of NC.
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http://dx.doi.org/10.1016/j.sleep.2011.01.010DOI Listing
June 2011

Premature ageing of the immune system underlies immunodeficiency in ataxia telangiectasia.

Clin Immunol 2011 Jul 13;140(1):26-36. Epub 2011 Mar 13.

Immunology Laboratory, Department of Pathology, Papworth Hospital NHS Foundation Trust, Cambridge University Health Partners, Cambridge CB23 3RE, UK.

ATM kinase modulates pathways implicated in premature ageing and ATM genotype predicts survival, yet immunodeficiency in ataxia telangiectasia is regarded as mild and unrelated to age. We address this paradox in a molecularly characterised sequential adult cohort with classical and mild variant ataxia telangiectasia. Immunodeficiency has the characteristics of premature ageing across multiple cellular and molecular immune parameters. This immune ageing occurs without previous CMV infection. Age predicts immunodeficiency in genetically homogeneous ataxia telangiectasia, and in comparison with controls, calendar age is exceeded by immunological age defined by thymic naïve CD4+ T cell levels. Applying ataxia telangiectasia as a model of immune ageing, pneumococcal vaccine responses, characteristically deficient in physiological ageing, are predicted by thymic naïve CD4+ T cell levels. These data suggest inherited defects of DNA repair may provide valuable insight into physiological ageing. Thymic naïve CD4+ T cells may provide a biomarker for vaccine responsiveness in elderly cohorts.
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http://dx.doi.org/10.1016/j.clim.2011.03.007DOI Listing
July 2011

Hypoxic challenge assessment in individuals with obstructive sleep apnea.

Sleep Med 2011 Feb 22;12(2):158-62. Epub 2011 Jan 22.

Respiratory Support and Sleep Centre, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge CB23 3RE, UK.

Background: The degree of arterial hypoxemia during air travel in individuals with obstructive sleep apnea (OSA) is not known. The Aerospace Medical Association considers a ground level arterial oxygen tension (PaO₂) above 9.3 kPa as safe before air travel.

Methods: Fifteen subjects with untreated OSA (mean apnea-hypopnea index [AHI] 43/h) and 14 with treated OSA (mean AHI on CPAP 1.9/h) completed an assessment including hypoxic challenge test (HCT). The groups had similar mean age, mean BMI and pre-treatment OSA severity.

Results: Four subjects, all in the untreated group and with resting PaO₂ >9.3 kPa and oxygen saturation (SpO₂) >95%, had a positive HCT (PaO₂ <6.6 kPa and/or SpO₂ <85%). The PaO₂ at the end of the HCT was significantly correlated with the minimum overnight SpO₂ (r=.754, p=.002) but not with the daytime PaO₂ and SpO₂. Using a cut off value of 65%, the minimum overnight SpO₂ had positive and negative predictive values of 57% and 100% respectively.

Conclusions: OSA can be an additional risk factor for developing significant arterial hypoxemia during HCT. Baseline PaO₂ and SpO₂ did not predict arterial hypoxemia during the HCT. Minimum overnight SpO₂ <65% may be used as a cut off to advise further assessment. Effective treatment of OSA seems to be the best option before air travel.
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http://dx.doi.org/10.1016/j.sleep.2010.06.009DOI Listing
February 2011

Asymptomatic sleep abnormalities are a common early feature in patients with Huntington's disease.

Curr Neurol Neurosci Rep 2011 Apr;11(2):211-7

Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.

Huntington's disease (HD) is a fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric disturbance. In this article, we used polysomnography, actigraphy and a variety of validated questionnaires to ascertain the extent to which sleep changes are identifiable and measurable in mild stage HD, and importantly, to see whether patients are negatively impacted by the changes in their sleep. We found significant differences in sleep architecture and sleep efficiency in patients compared with controls using polysomnography. However, patient scores on the Functional Outcomes of Sleep Questionnaire, Medical Outcomes of Sleep Scale, and Epworth Sleepiness Scale were not significantly different to controls. These results suggest that although marked changes in sleep architecture are present in early HD and can be detected using polysomnography, patients do not necessarily recognize or report these abnormalities.
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http://dx.doi.org/10.1007/s11910-010-0163-xDOI Listing
April 2011

Is there an alternative to pre-flight hypoxic challenge testing in scoliotic patients?

Respir Med 2010 Oct;104(10):1566-70

Respiratory Support and Sleep Centre, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, UK.

Introduction: Hypoxic challenge testing (HCT) is not readily available in all hospitals. It has recently been shown that resting oximetry does not reliably predict the results of HCT in patients with extrapulmonary restrictive lung disease. We assessed other clinical tests to see if they might be used as an alternative screen for HCT.

Methods: People with primary thoracic scoliosis were recruited. Resting SpO(2), arterial blood gases (ABG's), lung function and shuttle walking test (SWT) were measured. All subjects underwent HCT breathing an inhaled oxygen fraction of 15% for 20 min, or until SpO(2) fell below 85%, when ABG's were taken.

Results: Fourteen people (5 male) with thoracic scoliosis, Cobb angle 93 (31) degrees , aged 65 (8.5) years, FEV(1) 0.86 (0.4) L, FVC 1.2 (0.4)L were studied. The resting SpO(2) was 96 (2) %, PaO(2) 9.2 (1) kPa and PaCO(2) 6.1 (0.4) kPa. HCT was positive in 11 subjects (PaO(2) <6.6 kPa). Eight of 11 HCT positive subjects had a resting SpO(2) > 95%. Positive correlation was found between SpO(2) at SWT termination and PaO(2) following HCT (r = 0.56, p = 0.02). Those with saturations of 92% or under at SWT termination had positive HCT.

Conclusions: Despite normal resting SpO(2) subjects with thoracic scoliosis may have positive HCT. Current recommendations for air travel do not accurately identify these people. Desaturation following a SWT may provide a useful screening tool, however a low threshold for performing HCT on people with thoracic scoliosis prior to air travel is warranted.
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http://dx.doi.org/10.1016/j.rmed.2010.05.007DOI Listing
October 2010

Long-term non-invasive ventilation to manage persistent ventilatory failure after COPD exacerbation.

Respirology 2010 Jul 9;15(5):818-22. Epub 2010 Jun 9.

Respiratory Support and Sleep Centre, Papworth Hospital NHS Foundation Trust, Cambridge, UK.

Background And Objective: Patients with ventilatory failure at discharge from hospital following an exacerbation of COPD (ECOPD) have increased work of breathing and reduced inspiratory muscle strength compared with those with a normal arterial carbon dioxide tension (PaCO(2)). They also have a significantly worse prognosis. Long-term non-invasive positive pressure ventilation (NIPPV) may offer a treatment strategy but benefits have not been established.

Methods: We examined the outcomes of 35 patients, with a PaCO(2) >7.5 kPa and normal pH, following hospital admission with an ECOPD. Patients were initiated on long-term NIPPV. Our aims were to establish if NIPPV was tolerated and to describe the effects on ventilatory parameters.

Results: Daytime arterial blood gases and nocturnal ventilatory parameters improved significantly on NIPPV. Diurnal PaO(2), self-ventilating, rose from (mean (SD)) 7.3 (1.8) to 8.1 (0.9) kPa (P = 0.005) and PaCO(2) fell from 8.8 (1.3) to 7.3 (0.8) kPa (P
Conclusions: NIPPV was well tolerated in this group and appears to improve ventilation. Our preliminary data support further investigation of NIPPV in patients who remain hypercapnic after hospital admission with ECOPD.
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http://dx.doi.org/10.1111/j.1440-1843.2010.01787.xDOI Listing
July 2010

Weaning from prolonged invasive ventilation in motor neuron disease: analysis of outcomes and survival.

J Neurol Neurosurg Psychiatry 2011 Jun 14;82(6):643-5. Epub 2010 Apr 14.

Respiratory Support and Sleep Centre, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge CB23 3RE, UK.

Introduction: Non-invasive ventilation (NIV) improves prognosis in patients with motor neuron disease (MND) in the absence of major bulbar involvement. However, some experience a rapid and unexpected decline in respiratory function and may undergo emergency tracheal intubation. Weaning from invasive ventilation can be difficult, and reported independence from invasive ventilation is uncommon with poor prognosis. The outcomes of patients with MND referred to a specialist weaning service following emergency tracheal intubation were examined and compared with MND patients electively initiating NIV.

Methods: A case note review was performed on all patients with MND invasively ventilated and referred to a specialist weaning service between 1992 and 2007. Outcomes were compared with those electively commenced on NIV during the same period.

Results: Thirty patients were referred for weaning from invasive ventilation which was started in 17 before MND was diagnosed. Fourteen patients (47%) were weaned from invasive ventilation but still required NIV, 13 failed to wean, and three died. Seventeen were discharged home from hospital. The median survival from tracheal intubation was 13.7 months (95% CI 0 to 30.8) for those previously diagnosed and 7.2 months (95% CI 5.1 to 9.4) for those not previously known to have MND. Comparison with patients initiated electively on NIV demonstrated similar survival estimates to that from emergency intubation (median 9.4 (95% CI 6.9 to 12.0) vs 7.8 (95% CI 2.6 to 12.9) months respectively).

Conclusion: The prognosis in MND following acute respiratory failure and intubation is not always complete ventilator dependence if patients are offered a comprehensive weaning programme.
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http://dx.doi.org/10.1136/jnnp.2009.193631DOI Listing
June 2011

Association of idiopathic rapid eye movement sleep behavior disorder in an adult with persistent, childhood onset rhythmic movement disorder.

J Clin Sleep Med 2009 Aug;5(4):374-5

Westmead Hospital, Sydney, Australia.

We present a case of a 41-year-old man with the association of REM sleep behavior disorder (RBD) and rhythmic movement disorder (RMD). The RMD had a childhood onset and persisted into adulthood. The RMD worsened with the development of RBD and has persisted despite successful treatment of RBD. However, the pathogenesis of RMD remains unclear and the movements have been suggested to play a maturational role as part of psychomotor development by stimulating the vestibular apparatus. Current models underlying the control of REM sleep may need to be refined to explain the observed association of RBD and RMD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725259PMC
August 2009

Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam.

J Clin Sleep Med 2009 Jun;5(3):235-9

Regional Centre for Neurosciences, Newcastle General Hospital, Newcastle upon Tyne, UK.

Study Objectives: REM sleep behavior disorder (RBD) is characterized by loss of the normal muscle atonia during REM sleep associated with disruptive motor activity related to the acting out of dreams. There is frequently injury to the patient or bed partner, and treatment is usually required. Clonazepam has been the first-line therapy for many years, with 2 large case series reporting efficacy with few side effects in the majority of patients. However, long-acting hypnotics in the elderly or those with cognitive impairment can be associated with adverse events especially unacceptable daytime sedation, confusion, and exacerbation of existing sleep apnea.

Methods: We reviewed 39 patients with confirmed RBD who were treated within our regional sleep center, assessing both efficacy and side effects of drug therapies.

Results: Adverse effects were reported by 58% of the patients using clonazepam, with 50% either discontinuing the drug or reducing the dose. This prompted us review the side effects of clonazepam in detail and to look for alternative therapies. We report several novel and effective therapies, in particular zopiclone, in a series of patients under long-term follow-up for RBD.

Conclusions: There are alternatives to clonazepam therapy for RBD which can be as effective and may be better tolerated.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699168PMC
June 2009

Sleep violence.

Authors:
John M Shneerson

Br J Hosp Med (Lond) 2009 Jun;70(6):332-5

Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge CB23 3RE.

Violence during sleep is more common than is usually thought and has characteristic clinical features. These reflect the altered cerebral activity during sleep as well as the specific pathophysiology of the underlying sleep disorder. There are often forensic as well as clinical implications of violence during sleep which need careful assessment.
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http://dx.doi.org/10.12968/hmed.2009.70.6.332DOI Listing
June 2009

Successful treatment of REM sleep behavior disorder with sodium oxybate.

Authors:
John M Shneerson

Clin Neuropharmacol 2009 May-Jun;32(3):158-9

Respiratory Support and Sleep Centre, Papworth Hospital, Cambridge, England.

Objectives: To identify the effectiveness of sodium oxybate in treating the rapid eye movement sleep behavior disorder (RBD).

Methods: Report of effectiveness of sodium oxybate in a patient with severe RBD who was unresponsive to all other standard medication.

Results: The patient's severe symptoms had persisted unchanged for 5 years despite multiple drug treatments. They responded promptly to low-dose sodium oxybate treatment with video confirmation of cessation of physical activities during sleep. This improvement was maintained during 12 months of follow-up.

Conclusions: These novel findings indicate that sodium oxybate should be considered in RBD when other treatments are ineffective or poorly tolerated. They also suggest that RBD and cataplexy may in part share a common pathophysiology.
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http://dx.doi.org/10.1097/WNF.0b013e318193e394DOI Listing
August 2009

Effect of treatment with continuous positive airway pressure or oxygen on sleep-disordered breathing in patients with heart failure: results of the Sleep Events, Arrhythmias, and Respiratory Analysis in Chronic Heart Failure (SEARCH) study.

Congest Heart Fail 2008 Jul-Aug;14(4):197-201

The Ohio State University Heart Center, Columbus, OH 43210, USA.

The response to sleep-disordered breathing (SDB)-directed therapy was evaluated using the Clear Path home-based monitoring system. There were 26 patients with heart failure enrolled in the Sleep Events, Arrhythmias, and Respiratory Analysis in Chronic Heart Failure (SEARCH) study with SDB requiring treatment (apnea-hypopnea index [AHI] >or=15 events/h). Patients were monitored using both standard polysomnography and the Clear Path system to determine the change in SDB parameters before and after initiation of therapy. Accuracy of the Clear Path system compared with polysomnography was >or=87% to detect SDB events. A marked reduction in the mean number of sleep time respiratory disturbances was observed by both techniques after the initiation of SDB-directed therapy, and 21 patients (87.5%) experienced a 16.7-events/h mean reduction in AHI. Thus, the Clear Path system appears to be a useful device to monitor response to SDB-directed treatment for apnea in patients with heart failure.
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http://dx.doi.org/10.1111/j.1751-7133.2008.07841.xDOI Listing
November 2008

REM sleep behaviour disorder treated with melatonin in a patient with Alzheimer's disease.

Clin Neurol Neurosurg 2008 May 4;110(5):492-5. Epub 2008 Mar 4.

Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, United Kingdom.

We report a case of a 68-year-old man with probable Alzheimer's disease who developed rapid eye movement (REM) sleep behaviour disorder. This was confirmed with polysomnography but the patient also had some sleep apnea, which prevented the use of clonazepam for treatment. Melatonin was successfully used as an alternative treatment.
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http://dx.doi.org/10.1016/j.clineuro.2008.01.004DOI Listing
May 2008

Idiopathic hypersomnia: a study of 77 cases.

Sleep 2007 Oct;30(10):1274-81

Respiratory Support and Sleep Centre, Papworth Hospital Papworth Everard, Cambridge, UK.

Study Objectives: To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment.

Setting: The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK.

Patients And Design: A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years.

Measurements And Results: Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs.

Conclusions: Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve.
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http://dx.doi.org/10.1093/sleep/30.10.1274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266276PMC
October 2007

Screening the human prepro-orexin gene in a single-centre narcolepsy cohort.

Sleep Med 2007 Aug 18;8(5):498-502. Epub 2007 Jun 18.

Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, Cambridgeshire, UK.

Background And Purpose: Although the orexin system has an established role in narcolepsy, the mechanism of orexin deficiency in human cases is unknown. The strong association with human leukocyte antigen (HLA) DQB1*0602 suggests an autoimmune basis, but supporting evidence is lacking. Although data indicate that HLA status is not the sole genetic factor, only a single case of a functional orexin system mutation has been discovered, in a study with a selection bias designed to increase yield. In this study, we examined the prepro-orexin gene for mutations in a cohort of unrelated patients with narcolepsy from a national UK referral centre.

Patients And Methods: Subjects with a diagnosis of narcolepsy were recruited from a patient database. DNA samples were obtained using buccal smear kits. The prepro-orexin gene was amplified using polymerase chain reactions and screened for polymorphisms and mutations.

Results: Eighty-one patients were recruited, of whom 69 provided DNA samples. A previously described intronic single nucleotide polymorphism, of unlikely significance, was identified in one subject who had typical clinical and electrophysiological features of narcolepsy. It was located 16 base pairs downstream from exon 1. No other mutations were found.

Conclusion: This result supports existing evidence which indicates that mutations of the prepro-orexin gene are rare and that the genetic contribution to the aetiology of human narcolepsy is likely to be complex.
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http://dx.doi.org/10.1016/j.sleep.2006.11.016DOI Listing
August 2007

Severe chronic sleep-related neurogenic tachypnea.

J Clin Sleep Med 2005 Apr;1(2):167-8

Sleep Centre, Papworth Hospital, Cambridge, United Kingdom.

We report a chronic and severe case of sleep-related neurogenic tachypnea that occurred after head injury and preceding the use of medications known to suppress the respiratory system. Failure to acknowledge or explain the patient's sleep behavior had previously contributed to her depression and anxiety. She accepted that her respiratory abnormality in sleep is of little prognostic significance. Her medication was not changed, and no treatment was initiated. The patient took comfort from the polysomnography evidence shown to her and was greatly reassured.
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April 2005

Validation and clinical utility of a simple in-home testing tool for sleep-disordered breathing and arrhythmias in heart failure: results of the Sleep Events, Arrhythmias, and Respiratory Analysis in Congestive Heart Failure (SEARCH) study.

Congest Heart Fail 2006 Sep-Oct;12(5):241-7; quiz 248-9

The Ohio State University Heart Center, Davis Heart & Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210-1252, USA.

Fifty patients with New York Heart Association class III systolic heart failure were enrolled in this prospective multicenter study that compared the diagnostic accuracy of a home-based cardiorespiratory testing system with standard attended polysomnography. Patients underwent at least 2 nights of evaluation and were scored by blinded observers. At diagnostic cutoff points of > or =5, > or =10, and > or =15 events per hour for respiratory disturbance severity, polysomnography demonstrated a sleep-disordered breathing prevalence of 69%, 59%, and 49%, respectively. Compared with polysomnography, the cardiorespiratory testing system demonstrated predictive accuracies of 73%, 73%, and 75%, which improved to 87%, 87%, and 83%, respectively, when analysis of covariance suggested reanalysis omitting one site's data. The system accurately identified both suspected and unsuspected arrhythmias. The device was judged by 80% of patients to be easy or very easy to use, and 74% of patients expressed a preference for the in-home system. Therefore, this system represents a reasonable home testing device in these patients.
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http://dx.doi.org/10.1111/j.1527-5299.2006.05693.xDOI Listing
November 2006

Rhythmic movement disorder (head banging) in an adult during rapid eye movement sleep.

Mov Disord 2006 Jun;21(6):866-7

Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, Cambridge, United Kingdom.

Sleep-related rhythmic movements (head banging or body rocking) are extremely common in normal infants and young children, but less than 5% of children over the age of 5 years old exhibit these stereotyped motor behaviors. They characteristically occur during drowsiness or sleep onset rather than in deep sleep or rapid eye movement (REM) sleep. We present a 27-year-old man with typical rhythmic movement disorder that had persisted into adult life and was restricted to REM sleep. This man is the oldest subject with this presentation reported to date and highlights the importance of recognizing this nocturnal movement disorder when it does occur in adults.
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http://dx.doi.org/10.1002/mds.20847DOI Listing
June 2006

Prolonged invasive ventilation following acute ventilatory failure in COPD: weaning results, survival, and the role of noninvasive ventilation.

Chest 2006 Jan;129(1):133-9

Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, Cambridge, UK CB3 8RE.

Background: Invasive ventilation for COPD has significant mortality, and weaning can be difficult. At Papworth Hospital, we provide a specialist weaning service using noninvasive ventilation (NIV) for patients requiring prolonged invasive ventilation after recovery from acute illness. We analyzed our results for patients with COPD to identify factors associated with weaning outcome and survival.

Methods: A retrospective analysis was conducted of COPD patients admitted for weaning from invasive ventilation, from 1992 to 2003. Weaning success and survival were assessed. Associations were sought between these outcomes and age, sex, spirometry, arterial blood gas levels, APACHE (acute physiology and chronic health evaluation) II score, length of stay (LOS), and the use of NIV and long-term oxygen therapy.

Results: Sixty-seven patients were identified, all of whom were receiving tracheostomy ventilation on transfer to the Respiratory Support and Sleep Centre (RSSC). Sixty-four patients (95.5%) were weaned, and 62 patients survived to hospital discharge. NIV was used in weaning 40 patients and in the long term in 25 patients. Median survival was 2.5 years (interquartile range, 0.7 to 4.6 years). One-year, 2-year, and 5-year survival rates were 68%, 54%, and 25%, respectively. Long-term survival was inversely associated with age and LOS in the ICU and the RSSC. The provision of maintenance NIV after weaning was associated with better long-term survival, independent of age and LOS (hazard rate, 0.48; p = 0.03).

Conclusions: These results demonstrate that a specialist multidisciplinary approach, including the use of NIV, can be successful in weaning most COPD patients from prolonged invasive ventilation. The data also suggest that long-term NIV may improve survival in selected patients.
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http://dx.doi.org/10.1378/chest.129.1.133DOI Listing
January 2006

Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome.

J Psychopharmacol 2005 Nov;19(6):647-60

Psychopharmacology Research Unit, Centre for Neuroscience Research, King's College London, London, UK.

Fourteen patients (7 male, 7 female, 22-63 years), classified as having chronic fatigue syndrome (CFS), but without concurrent major depression, significant sleepiness or use of psychoactive medication, completed a double-blind, placebo-controlled, crossover study of the effects of the selective wakefulness-promoting agent, modafinil (200 and 400mg/day). The treatment periods were each 20 days, with washout periods of 2 weeks. The primary aim was to determine effects on cognition and the secondary aim was to determine effects on self-ratings of fatigue, quality of life and mood. Modafinil had mixed effects in two cognitive tasks. In a test of sustained attention, treatment with 200mg reduced the latency to correctly detect sequences, but 400mg increased the number of missed targets. In a test of spatial planning, the 200mg dose resulted in a slower initial thinking time for the easiest part of the task, whereas 400mg reduced the initial thinking time for the hardest part of the test. Lastly, in a test of mental flexibility and one of motor speed, patients performed worse whilst on modafinil (400mg), compared with the placebo period. No effects were observed on the performance of other psychometric tests or on self-ratings of fatigue, quality of life or mood, but this may have been due to insufficient statistical power. It is discussed whether the limited and mixed cognitive effects that we observed could have occurred by chance, or whether a subgroup of CFS patients with daytime sleepiness would have shown greater benefits.
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http://dx.doi.org/10.1177/0269881105056531DOI Listing
November 2005

The validation of a new actigraphy system for the measurement of periodic leg movements in sleep.

Sleep Med 2005 Nov 31;6(6):507-13. Epub 2005 Mar 31.

Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, UK.

Background And Purpose: To determine the accuracy of a new actigraphy system for the measurement of periodic leg movements (PLMs). Continuous measurements of leg movements, made overnight, are essential to diagnose and monitor treatment for PLMs. We have developed the Actiwatch with Cambridge Neuro-Technology Ltd (Cambridge, UK) to detect leg movements consistent with PLMs, to record these movements from both feet over three consecutive nights and to report standard indices of PLMs. We describe three studies designed to validate this device.

Patients And Methods: The Actiwatch was assessed on a bench model across a range of movement amplitudes. The level of agreement on individual movements between the Actiwatch and bilateral anterior tibialis electromyography (BATEMG) measures was assessed in 199 epochs from five patients with known PLMs. The ability of the Actiwatch to correctly identify patients with PLMs was assessed in a comparison with polysomnography (PSG) in 50 consecutive patients investigated in the sleep laboratory.

Results: The Actiwatch detected all mechanically generated movements (100% sensitivity and 100% specificity) on the bench test. On individual movements BATEMG measurement and the Actiwatch agreed on 94% of epochs. The sensitivity and specificity of the Actiwatch to detect leg movements in severe PLMs as defined by BATEMG (PLMI>or=25) are high (100% sensitive and 97% specific). Our bilateral system gave better agreement with BATEMG than previous systems but the two measures are still not interchangeable.

Conclusions: EMG is only a surrogate measure of limb movement and indices measured in this way correlate poorly with symptoms. We have demonstrated that the Actiwatch faithfully records movement, which offers the potential to reassess the relationships between limb movement indices and symptoms. This which offers a convenient and economical alternative to PSG in the study of large populations to increase our understanding of the epidemiology and clinical significance of PLMs.
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http://dx.doi.org/10.1016/j.sleep.2004.12.010DOI Listing
November 2005

Cognitive effects of modafinil in student volunteers may depend on IQ.

Pharmacol Biochem Behav 2005 Sep 2;82(1):133-9. Epub 2005 Sep 2.

Psychopharmacology Research Unit, Centre for Neuroscience Research, King's College London, London, UK.

The results of two previous studies on the effects of modafinil, a selective wakefulness-promoting agent, in healthy university students were combined in a retrospective analysis. This allowed determination of whether the effects of modafinil were dependent on IQ and whether the larger sample size (n=89) would reveal more cognitive benefits. A battery of cognitive tests was completed 2-3 h after dosing. In the whole sample, modafinil (200 mg) significantly reduced the number of missed targets in a test of sustained attention (RVIP). However, interestingly, several interactions between modafinil and IQ emerged. Modafinil (100 and 200 mg) significantly improved target sensitivity in the RVIP test, but only in the group of 'lower' IQ (mean+/-sem=106+/-0.6), not in the 'higher' IQ group (mean+/-sem=115.5+/-0.5). Furthermore, there were significant modafinil x IQ interactions in two further tests. Modafinil significantly reduced speed of responding in a colour naming of dots, and in clock drawing, but only in the 'lower' IQ group. Thus, the cognitive benefits of modafinil seem particularly marked in tests of vigilance and speed, in which sleepiness would be an important factor. Furthermore, the results indicate that high IQ may limit detection of modafinil's positive effects.
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http://dx.doi.org/10.1016/j.pbb.2005.07.019DOI Listing
September 2005
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