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BACKGROUND: Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined. METHODS: This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment). DISCUSSION: The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions. If this trial demonstrates the non-inferiority of therapist-guided iCBT-I, healthcare providers may be more confident recommending this treatment to their patients, contributing to the wider dissemination of CBT-I. TRIAL REGISTRATION: Trial registration number in the German Clinical Trials Register: DRKS00028153 ( https://drks.de/search/de/trial/DRKS00028153 ). Registered on 16th May 2023.

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BACKGROUND: The COVID-19 pandemic has caused a severe shortage of personal protective equipment (PPE), especially N95 respirators. Efficient, effective and economically feasible methods for large-scale PPE decontamination are urgently needed. AIMS: (1) to develop protocols for effectively decontaminating PPE using vaporized hydrogen peroxide (VHP); (2) to develop novel approaches that decrease set-up and take-down time while also increasing decontamination capacity; (3) to test decontamination efficiency for N95 respirators heavily contaminated by make-up or moisturizers. METHODS: We converted a decommissioned Biosafety Level 3 laboratory into a facility that could be used to decontaminate N95 respirators. N95 respirators were hung on metal racks, stacked in piles, placed in paper bags or covered with make-up or moisturizer. A VHP® VICTORY™ unit from STERIS was used to inject VHP into the facility. Biological and chemical indicators were used to validate the decontamination process. FINDINGS: N95 respirators individually hung on metal racks were successfully decontaminated using VHP. N95 respirators were also successfully decontaminated when placed in closed paper bags or if stacked in piles of up to six. Stacking reduced the time needed to arrange N95 respirators for decontamination by approximately two-thirds while almost tripling facility capacity. Make-up and moisturizer creams did not interfere with the decontamination process. CONCLUSIONS: Respirator stacking can reduce the hands-on time and increase decontamination capacity. When personalization is needed, respirators can be decontaminated in labelled paper bags. Make up or moisturizers do not appear to interfere with VHP decontamination.

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With adipose-derived stem cells being in the focus of research in regenerative medicine, the need arises for fast reliable cultivation protocols. We have tested the cultivation of human adipose-derived stem cells in endothelial cell growth medium prior to induction and differentiation, against the long-established use of DMEM/F12 medium-based cultivation protocols. We found that cultivation in endothelial cell growth medium not only accelerates growth before induction and differentiation, but also allows shorter induction and differentiation times than those following precultivation with DMEM/F12 medium with regard to the formation of mature adipocytes and to the viability undifferentiated cells. These results were first observed morphologically but could be confirmed by performing adiponectin ELISA and cell proliferation assays.

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OBJECTIVES: To describe the clinical and neuroradiological features of basilar impression in patients with osteogenesis imperfecta type IV. METHODS: Four patients with basilar impression were ascertained in a population study of osteogenesis imperfecta. All four had detailed clinical and neuroradiological examination with both CT and MRI of the craniocervical junction and posterior fossa structures. RESULTS: All four showed significant compression of the posterior fossa structures and surgical decompression was performed with relief of symptoms. CONCLUSION: Symptoms of cough headache and trigeminal neuralgia occurring in patients with osteogenesis imperfecta are indications for detailed clinical and neuroradiological investigation to document basilar impression.

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We described a profoundly intellectually disabled 24-year-old man with Wolf-Hirschhorn syndrome, left hemiplegia, epilepsy, atrophy of the right cerebral hemisphere, and dilatation of the right ventricle. The patient had a small ventricular septal defect, was wheelchair bound, and totally dependent. He had no speech, but vocalised to show his feelings. In this patient, the del(4)(p15) was subtle and arose due to the inheritance of a recombinant chromosome (4) from a maternal pericentric inversion-46,XX,inv(4) (p15.32q35). Fluorescence in situ hybridisation with probe D4S96 confirmed the deletion. This is the second case of Wolf-Hirschhorn syndrome resulting from a large pericentric inversion of chromosome 4.

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A 16-year-old girl presented with a unilateral third nerve palsy and predominant gray matter involvement on MR and positron emission tomography with fludeoxyglucose F 18. These findings were manifestations of gliomatosis cerebri. The antemortem diagnosis was made by partial temporal lobectomy.

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The author discusses a specific case to illustrate the problem of chronic, uncompensated asymmetrical vestibular function, which can present with seemingly bizarre symptoms. Simple guidelines to distinguish between organic and functional dizziness are offered.

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Lymphomatoid granulomatosis is an uncommon clinical problem and even more rarely presents to the ophthalmologist. A case is described in which a 60-year-old Fijian woman presented with sudden, sequential, complete visual loss in association with signs of scleritis. Direct eyewall biopsy and nasal mucosal biopsy confirmed the diagnosis of lymphomatoid granulomatosis. Despite intensive high-dose oral prednisone therapy her vision remained at no light perception and she developed recrudescence of disease necessitating the use of radiotherapy. All systemic investigations failed to show any other organ involvement by the disease process and she remains well. This is the first report of lymphomatoid granulomatosis presenting as sudden blindness.

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The vestibulo-ocular reflex and its suppression by fixation of a target rotating with the subject were tested in 18 subjects with congenital nystagmus using steps of constant velocity rotation and sinusoidal stimuli swept in frequency between 0.01 and 1.0 Hz. Responses to stopping stimuli were abnormal in waveform and of short duration in most subjects tested. This pattern was attributed to masking of the response by spontaneous eye movements and to adaptation. In contrast, during both oscillation in the dark and attempted suppression of the vestibulo-ocular reflex, all subjects had nystagmus that was modulated with the stimulus during all frequencies of stimulation. The phase relationship of the nystagmus to the motion stimulus was the same as in normal subjects. Estimates of the gain of the vestibulo-ocular reflex response were not meaningful because of contamination of the vestibular response by the congenital nystagmus waveforms. Modulation of amplitude and reversal of nystagmus in phase with the vestibular stimulus at all frequencies of oscillation were shown most clearly during attempted suppression of the vestibulo-ocular reflex. This finding is clinically useful because it establishes suppression as a test of the presence of vestibular function in congenital nystagmus.

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Ten patients with an accepted diagnosis of Friedreich's ataxia have been examined neuro-otologically, and oculomotor, vestibular and auditory function assessed. Brainstem auditory evoked potentials (BAEPs) were also recorded. A high incidence of various eye movement disorders was noted. Some of these were indicative of cerebellar dysfunction. Reduced vestibular function and impaired hearing were common to most of the patients. BAEPs were also abnormal in the majority; reasons underlying these abnormalities are discussed. Neuro-otologically, the patients did not constitute an homogeneous group. The findings cast doubt upon the accuracy and validity of the currently accepted criteria for the diagnosis and classification of the spinocerebellar degenerations.

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The effects of the "vestibular sedative" drug Flunarizine upon the oculomotor functions of pursuit and voluntary saccades and upon the vestibular response (to rotational stimuli) were assessed in twenty volunteer subjects. The study was then extended to three patients with chronic imbalance of central origin who had reported a beneficial symptomatic response to the drug. Three of the volunteer subjects were found to have a directional preponderance (presumed to arise from peripheral dysfunction). In the remaining seventeen normal subjects Flunarizine was found to reduce the amplitudes of fast phases of vestibular nystagmus. The directional preponderance in the other three subjects was redressed through production of fast phases which were of lower and more uniform amplitude. In the patients, in addition to a reduction in fast phase amplitude, there was a reduction or abolition of after nystagmus. In no case was any reduction in slow phase velocity observed. Pursuit and voluntary saccades were unaffected by the drug. It was concluded, on the basis that the fast phases of nystagmus are centrally generated, that Flunarizine has a central action rather than a depressant effect upon the vestibular end organ. In view of known oculomotor physiology and pharmacology it is proposed that vestibular sedatives act by depression of Type II vestibular neurons, and modification of the functional relationships between the vestibular nuclei, the perihypoglossal nuclei and the flocculus of the cerebellum. A trial of vestibular active drug is indicated particularly in patients in whom asymmetry of the vestibular response and/or abnormal after nystagmus is demonstrated.

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A patient with downbeat nystagmus and familial ataxia is described. The nystagmus was induced by static tilt away from normal upright posture, by linear acceleration of the head, and by convergence. It is inferred that the nystagmus was modulated by otolith-specific stimuli and not by stimulation of the canals. These findings demonstrate the role of otolith function in generation of eye movements in the vertical plane and support proposed interrelationships between otolith and vergence mechanisms. The nystagmus and associated oscillopsia were partially suppressed by treatment with clonazepam.

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We describe a patient with multiple sclerosis who experienced the Pulfrich illusion of elliptical motion of a target moving linearly when viewing the motion with one eye as opposed to the well recognised binocular manifestation of the phenomenon. The perception of the illusion was independent of the wave form or velocity characteristics of target motion or of retinal image position. We suggest that the occurrence of the phenomenon does not simply reflect delay in the visual system but is a function of an abnormality of perceptual interpretation of visual stimuli occurring at a high integrative level.

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Investigations were made of 16 patients with acquired pendular nystagmus and a further 32 cases reported in the literature were reviewed. Amongst our own patients two thirds had multiple sclerosis, almost one third a cerebrovascular accident or angioma and two had optic atrophy with squint. The nystagmus took forms which could be monocular or binocular, conjugate or disconjugate and could involve movements about single or multiple axes. Spectral analysis was used to characterise the amplitude and frequency of the movements and to estimate the degree of relationship (coherence) between movements of the two eyes or between movements of one eye about several axes. The oscillations ranged in frequency from 2·5 Hz to 6 Hz, with typical amplitudes between 3° and 5°. In a given patient all oscillations, regardless of plane, were highly synchronised. Somatic tremors of the upper limb, face and palate associated with the nystagmus were often at similar frequencies to the eye movement. The other ocular signs common to all our patients were the presence of squint with failure of convergence. Most patients also had skew deviation or internuclear ophthalmoplegia or both. The major oculomotor systems, that is, saccades, pursuit, optokinetic and vestibulo-ocular reflexes could be intact. It is inferred that the mechanism responsible for the pendular nystagmus lies at a level which is close to the oculomotor nuclei so that it can have monocular effects but is not part of the primary motor pathways. It is possible that this mechanism normally subserves maintenance of conjugate movement and posture of the eyes. The periodicity of the nystagmus is likely to arise from instability in a certain type(s) of neurone, for the associated somatic tremors have similar characteristics and yet involve very different neuronal muscular circuitry. Prognosis for cessation of the nystagmus is poor. In five patients with multiple sclerosis it was suppressed by intravenous hyoscine with, however, unacceptable subsequent side effects.

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The occurrence of spinal cord lesions in association with self-administration of heroin is a recognised entity in the United States of America which has not up to now been reported in British literature. Three cases are described, the literature reviewed and possible aetiological factors discussed.

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