Effects of acute nutritional ketosis during exercise in adults with glycogen storage disease type IIIa are phenotype-specific: An investigator-initiated, randomized, crossover study.

Glycogen storage disease type IIIa (GSDIIIa) is an inborn error of carbohydrate metabolism caused by a debranching enzyme deficiency. A subgroup of GSDIIIa patients develops severe myopathy. The purpose of this study was to investigate whether acute nutritional ketosis (ANK) in response to ketone-ester (KE) ingestion is effective to deliver oxidative substrate to exercising muscle in GSDIIIa patients. This was an investigator-initiated, researcher-blinded, randomized, crossover study in six adult GSDIIIa patients. Prior to exercise subjects ingested a carbohydrate drink (~66 g, CHO) or a ketone-ester (395 mg/kg, KE) + carbohydrate drink (30 g, KE + CHO). Subjects performed 15-minute cycling exercise on an upright ergometer followed by 10-minute supine cycling in a magnetic resonance (MR) scanner at two submaximal workloads (30% and 60% of individual maximum, respectively). Blood metabolites, indirect calorimetry data, and in vivo 31 P-MR spectra from quadriceps muscle were collected during exercise. KE + CHO induced ANK in all six subjects with median peak ßHB concentration of 2.6 mmol/L (range: 1.6-3.1). Subjects remained normoglycemic in both study arms, but delta glucose concentration was 2-fold lower in the KE + CHO arm. The respiratory exchange ratio did not increase in the KE + CHO arm when workload was doubled in subjects with overt myopathy. In vivo 31 P MR spectra showed a favorable change in quadriceps energetic state during exercise in the KE + CHO arm compared to CHO in subjects with overt myopathy. Effects of ANK during exercise are phenotype-specific in adult GSDIIIa patients. ANK presents a promising therapy in GSDIIIa patients with a severe myopathic phenotype. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03011203.

Compensatory Movement Patterns Are Based on Abnormal Activity of the Biceps Brachii and Posterior Deltoid Muscles in Patients with Symptomatic Rotator Cuff Tears.

BACKGROUND: Abnormal movement patterns due to compensatory mechanisms have been reported in patients with rotator cuff tears. The long head of the biceps tendon may especially be overactive and a source of pain and could induce abnormal muscle activation in these patients. It is still unknown why some patients with a rotator cuff tear develop complaints and others do not. QUESTIONS/PURPOSES: (1) Which shoulder muscles show a different activation pattern on electromyography (EMG) while performing the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with a symptomatic rotator cuff tear compared with age-matched controls with an intact rotator cuff? (2) Which shoulder muscles are coactivated on EMG while performing the FIT-HaNSA? METHODS: This comparative study included two groups of people aged 50 years and older: a group of patients with chronic symptomatic rotator cuff tears (confirmed by MRI or ultrasound with the exclusion of Patte stage 3 and massive rotator cuff tears) and a control group of volunteers without shoulder conditions. Starting January 2019, 12 patients with a chronic rotator cuff tear were consecutively recruited at the outpatient orthopaedic clinic. Eleven age-matched controls (randomly recruited by posters in the hospital) were included after assuring the absence of shoulder complaints and an intact rotator cuff on ultrasound imaging. The upper limb was examined using the FIT-HaNSA (score: 0 [worst] to 300 seconds [best]), shoulder-specific instruments, health-related quality of life, and EMG recordings of 10 shoulder girdle muscles while performing a tailored FIT-HaNSA. RESULTS: EMG (normalized root mean square amplitudes) revealed hyperactivity of the posterior deltoid and biceps brachii muscles during the upward phase in patients with rotator cuff tears compared with controls (posterior deltoid: 111% ± 6% versus 102% ± 10%, mean difference -9 [95% confidence interval -17 to -1]; p = 0.03; biceps brachii: 118% ± 7% versus 111% ± 6%, mean difference -7 [95% CI -13 to 0]; p = 0.04), and there was decreased activity during the downward phase in patients with rotator cuff tears compared with controls (posterior deltoid: 89% ± 6% versus 98% ± 10%, mean difference 9 [95% CI 1 to 17]; p = 0.03; biceps brachii: 82% ± 7% versus 89% ± 6%, mean difference 7 [95% CI 0 to 14]; p = 0.03). The posterior deltoid functioned less in conjunction with the other deltoid muscles, and lower coactivation was seen in the remaining intact rotator cuff muscles in the rotator cuff tear group than in the control group. CONCLUSION: Patients with a symptomatic rotator cuff tear show compensatory movement patterns based on abnormal activity of the biceps brachii and posterior deltoid muscles when compared with age-matched controls. The posterior deltoid functions less in conjunction with the other deltoid muscles, and lower coactivation was seen in the remaining intact rotator cuff muscles in the rotator cuff tear group than the control group. CLINICAL RELEVANCE: This study supports the potential benefit of addressing the long head biceps tendon in the treatment of patients with a symptomatic rotator cuff tear. Moreover, clinicians might use these findings for conservative treatment; the posterior deltoid can be specifically trained to help compensate for the deficient rotator cuff.

The importance of the intensive care unit environment in sleep-A study with healthy participants.

Sleep disruption is common among intensive care unit patients, with potentially detrimental consequences. Environmental factors are thought to play a central role in ICU sleep disruption, and so it is unclear why environmental interventions have shown limited improvements in objectively assessed sleep. In critically ill patients, it is difficult to isolate the influence of environmental factors from the varying contributions of non-environmental factors. We thus investigated the effects of the ICU environment on self-reported and objective sleep quality in 10 healthy nurses and doctors with no history of sleep pathology or current or past ICU employment participated. Their sleep at home, in an unfamiliar environment ('Control'), and in an active ICU ('ICU') was evaluated using polysomnography and the Richard-Campbell Sleep Questionnaire. Environmental sound, light and temperature exposure were measured continuously. We found that the control and ICU environment were noisier and warmer, but not darker than the home environment. Sleep on the ICU was perceived as qualitatively worse than in the home and control environment, despite relatively modest effects on polysomnography parameters compared with home sleep: mean total sleep times were reduced by 48 min, mean rapid eye movement sleep latency increased by 45 min, and the arousal index increased by 9. Arousability to an awake state by sound was similar. Our results suggest that the ICU environment plays a significant but partial role in objectively assessed ICU sleep impairment in patients, which may explain the limited improvement of objectively assessed sleep after environmental interventions.

Dental side effects of long-term obstructive sleep apnea therapy: a 10-year follow-up study.

OBJECTIVES: Patients with obstructive sleep apnea (OSA) are usually treated with either mandibular advancement device (MAD) or continuous positive airway pressure (CPAP) therapy. The objective of this study is to evaluate changes in dental occlusion associated with long-term MAD and CPAP therapy. MATERIALS AND METHODS: Data from 14 OSA patients using MAD and 17 OSA patients using CPAP therapy were evaluated at baseline, 2-year and 10-year follow-up. Changes in dental occlusion were analyzed from dental plaster casts with a digital sliding caliper. RESULTS: At 2-year follow-up, MAD therapy resulted in significant dental changes when compared with baseline values. In MAD therapy, overjet and overbite decreased with 1.1 ± 1.8 mm and 1.1 ± 1.2 mm respectively. With CPAP therapy overjet and overbite decreased significantly with 0.2 ± 0.5 mm and 0.3 ± 0.5 mm, respectively. Both groups also showed significant changes in molar occlusion. After a 10-year follow-up, significant and more pronounced changes were seen in overjet and overbite. In MAD therapy, overjet and overbite decreased with 3.5 ± 1.5 mm and 2.9 ± 1.5 mm respectively when compared with baseline values. In CPAP therapy, overjet and overbite decreased with 0.7 ± 1.5 mm and 0.8 ± 1.4 mm respectively when compared with baseline values. CONCLUSIONS: This study demonstrates that MAD and CPAP therapy result in significant changes in dental occlusion. These changes appear progressive and more pronounced with MAD compared to CPAP therapy. CLINICAL RELEVANCE: Long-term OSA treatment results in significant dental side effects that may progress over time. Informed consent is fundamental before starting MAD treatment and individualized long-term follow-up is of eminent importance.

Validity and Predictive Value of a Portable Two-Channel Sleep-Screening Tool in the Identification of Sleep Apnea in Patients With Heart Failure.

BACKGROUND: Sleep apnea is an important comorbidity in heart failure (HF) and is associated with an adverse outcome. Diagnosing sleep apnea is difficult, and polysomnography, considered to be the criterion standard, is not widely available. We assessed the validity of a portable 2-channel sleep-screening tool for the identification of sleep apnea in patients with HF. METHODS AND RESULTS: One hundred patients with stable HF had simultaneous recordings of home-based polysomnography and the screening tool (Apnealink). To compare the apnea-hypopnea index of the screening tool with polysomnography, intraclass correlation (ICC), sensitivity, and specificity were calculated, and a Bland-Altman plot and receiver operating characteristic (ROC) curves were constructed. Ninety valid measurements with the screening tool were obtained (mean age 65.5 ± 11.0 y, 72% male, mean left ventricular ejection fraction 34.6 ± 11.0%). Agreement between the screening tool and polysomnography was high (ICC 0.85). The optimal cutoff value was apnea-hypopnea index ≥15/h (area under the ROC curve 0.94). Sensitivity and specificity were 92.9% and 91.9%, respectively. CONCLUSIONS: The screening tool is useful in excluding the presence of sleep apnea in HF patients to refer only high-risk patients for more extensive polysomnography. This method may potentially reduce the need for the more expensive polysomnography.

Intensive care unit depth of sleep: proof of concept of a simple electroencephalography index in the non-sedated.

INTRODUCTION: Intensive care unit (ICU) patients are known to experience severely disturbed sleep, with possible detrimental effects on short- and long- term outcomes. Investigation into the exact causes and effects of disturbed sleep has been hampered by cumbersome and time consuming methods of measuring and staging sleep. We introduce a novel method for ICU depth of sleep analysis, the ICU depth of sleep index (IDOS index), using single channel electroencephalography (EEG) and apply it to outpatient recordings. A proof of concept is shown in non-sedated ICU patients. METHODS: Polysomnographic (PSG) recordings of five ICU patients and 15 healthy outpatients were analyzed using the IDOS index, based on the ratio between gamma and delta band power. Manual selection of thresholds was used to classify data as either wake, sleep or slow wave sleep (SWS). This classification was compared to visual sleep scoring by Rechtschaffen & Kales criteria in normal outpatient recordings and ICU recordings to illustrate face validity of the IDOS index. RESULTS: When reduced to two or three classes, the scoring of sleep by IDOS index and manual scoring show high agreement for normal sleep recordings. The obtained overall agreements, as quantified by the kappa coefficient, were 0.84 for sleep/wake classification and 0.82 for classification into three classes (wake, non-SWS and SWS). Sensitivity and specificity were highest for the wake state (93% and 93%, respectively) and lowest for SWS (82% and 76%, respectively). For ICU recordings, agreement was similar to agreement between visual scorers previously reported in literature. CONCLUSIONS: Besides the most satisfying visual resemblance with manually scored normal PSG recordings, the established face-validity of the IDOS index as an estimator of depth of sleep was excellent. This technique enables real-time, automated, single channel visualization of depth of sleep, facilitating the monitoring of sleep in the ICU.

Effects of Upper Blepharoplasty Techniques on Headaches, Eyebrow Position, and Electromyographic Outcomes: A Randomized Controlled Trial.

The aim of this study was to assess changes in headaches, eyebrow height, and electromyographic (EMG) outcomes of the frontalis and orbicularis oculi muscles, after an upper blepharoplasty with or without resecting a strip of orbicularis oculi muscle. In a randomized controlled trial, 54 patients received an upper blepharoplasty involving either only removing skin (group A) or removing skin with an additional strip of orbicularis muscle (group B). Preoperative, and 6 and 12 months postoperative headache complaints were assessed using the HIT-6 scores and eyebrow heights were measured on standardised photographs. Surface EMG measurements, i.e., electrical activity and muscle fatigue, were assessed for the frontalis and orbicularis oculi muscles preoperatively and 2, 6, and 12 months postoperatively. Significantly fewer headaches were reported following a blepharoplasty. The eyebrow height had decreased, but did not differ between groups. Regarding the surface EMG measurements, only group A's frontalis muscle electrical activity had decreased significantly during maximal contraction 12 months after surgery (80 vs. 39 mV, p = 0.026). Fatigue of both the frontalis and the orbicularis oculi muscles did not change significantly postoperatively compared to baseline. EMG differences between groups were minor and clinically insignificant. The eyebrow height decreased and patients reported less headaches after upper blepharoplasty irrespective of the used technique.

Fetal endoscopic myelomeningocele closure preserves segmental neurological function.

AIM: Our aim was to compare the effect of prenatal endoscopic with postnatal myelomeningocele closure (fetally operated spina bifida aperta [fSBA]) versus neonatally operated spina bifida aperta [nSBA]) on segmental neurological leg condition. METHOD: Between 2003 and 2009, the fetal surgical team (Department of Obstetrics, University of Bonn, Germany) performed 19 fetal endoscopic procedures. Three procedures resulted in fetal death, three procedures were interrupted by iatrogenic hemorrhages and 13 procedures were successful. We matched each successfully treated fSBA infant with another nSBA infant of the same age and level of lesion, resulting in 13 matched pairs (mean age 14 mo; SD 16 mo; f/m=1.6; female-16, male-10). Matched fSBA and nSBA pairs were compared in terms of segmental neurological function and leg muscle ultrasound density (MUD). We also determined intraindividual difference in MUD (dMUD) between myotomes caudal and cranial to the myelomeningocele (reflecting neuromuscular damage by the myelomeningocele) and compared dMUD between fSBA and nSBA infants. Finally, we correlated dMUD with segmental neurological function. RESULTS: We found that, on average, the fSBA group were born at a lower gestational age than the nSBA group (median 32 wks [range 25-34 wks] vs 39 wks [34-41 wks]; p=0.001) and experienced more complications (chorioamnionitis, premature rupture of the amniotic membranes, oligohydramnios, and infant respiratory distress syndrome necessitating intermittent positive-pressure ventilation). Neurological function was better preserved after fSBA than after nSBA (median motor and sensory gain of two segments; better preserved knee-jerk [p=0.006] and anal [p=0.032] reflexes). The dMUD was smaller in fSBA than in nSBA infants (mean difference 24, 95% confidence interval [CI] 15-33; p<0.05), which was associated with better preserved segmental muscle function. INTERPRETATION: Fetal endoscopic surgery is associated with spinal segmental neuroprotection, but it results in more complications. Before considering clinical implementation of fetal endoscopic myelomeningocele closure as standard care, the frequency of complications should be appropriately reduced and results assessed in larger groups over a longer period of time.

In children with Friedreich ataxia, muscle and ataxia parameters are associated.

AIM: In children with Friedreich ataxia (FRDA), ataxia is assessed using the surrogate marker the International Cooperative Ataxia Rating Scale (ICARS). We aimed to determine whether ICARS scores in children with FRDA are confounded by muscle weakness. METHOD: In 12 children with FRDA (10 males, two females; mean age 13 y 6 mo, SD 2 y 6 mo) and 12 age-matched children without FRDA (nine males; three females), we determined the association between muscle and ataxia parameters (i.e. muscle ultrasound density (MUD), muscle force, sensory evoked potentials, and ICARS scores). Children with FRDA were included on the basis of FXN gene analysis. Children in the comparison group were included on basis of uneventful pregnancy and normal cognitive and neurological development. RESULTS: In children with FRDA, muscle ultrasound density was homogeneously increased in the biceps, quadriceps, and tibialis anterior muscles (median 4SD). FRDA muscle weakness was significantly more pronounced in proximal than in distal muscles (-2SD vs -0.5SD respectively; p=0.004), with a stronger impairment of leg muscles than of arm muscles (-2SD vs -0. SD respectively; p=0.001). Comparing MUD between children with FRDA and an age-matched comparison group revealed a relatively strong increase in MUD in the proximal leg muscles in the FRDA group. Under the condition of persistently absent sensory evoked potentials, leg ICARS subscores in the FRDA group appeared to be positively associated with leg muscle force until a maximal plateau level of ICARS subscores was reached. INTERPRETATION: In children with FRDA, ataxia scales based on ICARS are confounded by muscle weakness. Longitudinal ICARS evaluations in children with FRDA do not necessarily indicate altered ataxia.

The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy.

PURPOSE: Pyridoxine-dependent epilepsy (PDE) is characterized by therapy-resistant seizures (TRS) responding to intravenous (IV) pyridoxine. PDE can be identified by increased urinary alpha-aminoadipic semialdehyde (α-AASA) concentrations and mutations in the ALDH7A1 (antiquitin) gene. Prompt recognition of PDE is important for treatment and prognosis of seizures. We aimed to determine whether immediate electroencephalography (EEG) alterations by pyridoxine-IV can identify PDE in neonates with TRS. METHODS: In 10 neonates with TRS, we compared online EEG alterations by pyridoxine-IV between PDE (n = 6) and non-PDE (n = 4). EEG segments were visually and digitally analyzed for average background amplitude and total power and relative power (background activity magnitude per frequency band and contribution of the frequency band to the spectrum). RESULTS: In 3 of 10 neonates with TRS (2 of 6 PDE and 1 of 4 non-PDE neonates), pyridoxine-IV caused flattening of the EEG amplitude and attenuation of epileptic activity. Quantitative EEG alterations by pyridoxine-IV consisted of (1) decreased central amplitude, p < 0.05 [PDE: median -30% (range -78% to -3%); non-PDE: -20% (range -45% to -12%)]; (2) unaltered relative power; (3) decreased total power, p < 0.05 [PDE: -31% (-77% to -1%); -27% (-73% to -13%); -35% (-56% to -8%) and non-PDE: -16% (-43% to -5%); -28% (-29% to -17%); -26% (-54% to -8%), in delta-, theta- and beta-frequency bands, respectively]; and (4) similar EEG responses in PDE and non-PDE. DISCUSSION: In neonates with TRS, pyridoxine-IV induces nonspecific EEG responses that neither identify nor exclude PDE. These data suggest that neonates with TRS should receive pyridoxine until PDE is fully excluded by metabolic and/or DNA analysis.

Development of muscle ultrasound density in healthy fetuses and infants.

Muscle ultrasound density (MUD) is a non-invasive parameter to indicate neuromuscular integrity in both children and adults. In healthy fetuses and infants, physiologic MUD values during development are still lacking. We therefore aimed to determine the physiologic, age-related MUD trend of biceps, quadriceps, tibialis anterior, hamstrings, gluteal and calf muscles, from pre- to the first year of postnatal life. To avoid a bias by pregnancy-related signal disturbances, we expressed fetal MUD as a ratio against bone ultrasound density. We used the full-term prenatal MUD ratio and the newborn postnatal MUD value as reference points, so that MUD development could be quantified from early pre- into postnatal life. Results: During the prenatal period, the total muscle group revealed a developmental MUD trend concerning a fetal increase in MUD-ratio from the 2nd trimester up to the end of the 3rd trimester [median increase: 27% (range 16-45), p < .001]. After birth, MUD-values increased up to the sixth month [median increase: 11% (range -7-27), p = 0.025] and stabilized thereafter. Additionally, there were also individual MUD characteristics per muscle group and developmental stage, such as relatively low MUD values of fetal hamstrings and high values of the paediatric gluteus muscles. These MUD trends are likely to concur with analogous developmentally, maturation-related alterations in the muscle water to peptide content ratios.

Long-term obstructive sleep apnea therapy: a 10-year follow-up of mandibular advancement device and continuous positive airway pressure.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder, commonly managed by either continuous positive airway pressure (CPAP) or a mandibular advancement device (MAD). Long-term follow-up and comparison regarding efficacy of these therapies is scarce. In this study the results of treatment, patient adherence, and satisfaction over a 10-year follow-up of these therapies are reported. METHODS: This is a longitudinal follow-up study taken from a subset of patients initially enrolled in a randomized controlled clinical trial of 103 patients with OSA (51 and 52 patients randomized for MAD and CPAP, respectively). After a 10-year follow-up period, 14 patients using MAD and 17 patients using CPAP could be evaluated for this longitudinal follow-up study. Data were analyzed at baseline, after 3 months and at 1-, 2-, and 10-year follow-up. All 31 patients with OSA underwent polysomnography and self-reported measurements. RESULTS: Polysomnography results showed a favorable outcome of both therapies at 10-year follow-up. At baseline, included patients in both groups did not significantly differ in apnea-hypopnea index (AHI) values. At 10-year follow-up, both the MAD and CPAP groups showed a significant reduction in AHI. At baseline the mean AHI in the MAD group was 31.7 ± 20.6 events/h whereas in the CPAP group it was 49.2 ± 26.1 events/h. At 10-year follow-up the mean AHI in the MAD group was 9.9 ± 10.3 events/h and in the CPAP group it was 3.4 ± 5.4 events/h. Both therapies resulted in a substantial improvement in self-reported neurobehavioral outcomes at 10-year follow-up. CONCLUSIONS: Both CPAP and MAD therapy demonstrate good and stable treatment effects after a 10-year follow-up period. Therefore, when indicated, both therapies are appropriate modalities for the long-term management of OSA. CLINICAL TRIAL REGISTRATION: Registry: Netherlands Trial Register; Name: Management of the Obstructive Sleep Apnea-Hypopnea Syndrome: Oral Appliance versus Continuous Positive Airway Pressure Therapy; Identifier: NL75; URL: https://www.trialregister.nl/trial/75.

Leg muscle strength is reduced and is associated with physical quality of life in Antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Physical quality of life is reduced in ANCA-associated vasculitis (AAV). This study aims to investigate whether this may be explained by reduced muscle strength and physical activity resulting from disease damage and steroid myopathy. METHODS: Forty-eight AAV patients were sequentially included from the outpatient clinic. Patients in different stages of disease and treatment underwent measurements of muscle strength and anthropometric parameters. Patients filled in physical activity (Baecke) and quality of life questionnaires (RAND-36) and carried an accelerometer for a week. Muscle strength and physical activity were compared to quality of life, prednisolone use and disease duration. RESULTS: Most AAV patients had lower knee extension (76%) and elbow flexion (67%) forces than expected based on healthy norms. Also, physical (P<0.001) and mental (P = 0.01) quality of life were significantly reduced compared to healthy norm values. Lower knee extension force (P = 0.009), younger age <70 (P<0.001) and relapse of vasculitis (P = 0.003) were associated with lower age-adjusted physical quality of life. Lower Baecke index (P = 0.006), higher prednisolone dose (P = 0.005) and ENT involvement (P = 0.006) were associated with lower age-adjusted mental quality of life. Leg muscle strength showed no association with current or cumulative prednisolone use. Disease duration was longer in patients with knee extension force below healthy norms (P = 0.006). CONCLUSION: Knee extension force and physical activity are positively associated with quality of life in AAV. Knee extension force decreases with longer disease duration, suggesting that disease- and treatment-related damage have a cumulative negative effect on muscle strength.

Lack of analgesic effects of transcranial pulsed electromagnetic field stimulation in neuropathic pain patients: A randomized double-blind crossover trial.

BACKGROUND: Neuromodulation is nowadays investigated as a promising method for pain relief. Research indicates that a single 30-minute stimulation with transcranial pulsed electromagnetic fields (tPEMF) can induce analgesic effects. However, it is unknown whether tPEMF can induce analgesia in neuropathic pain patients. OBJECTIVE: To evaluate the effect of tPEMF on spontaneous pain and heat pain in neuropathic pain patients. METHODS: This study had a randomized double-blind crossover design. Twenty neuropathic pain patients received 30-minutes of tPEMF and 30-minutes sham stimulation. Primary outcomes were pain intensity, pain aversion and heat pain. Secondary outcomes included affect, cognition, and motor function, to investigate safety, tolerability and putative working mechanisms of tPEMF. Outcomes were assessed before, during and after stimulation. RESULTS: No differences in analgesic effects between tPEMF and sham stimulation were found for pain intensity, pain aversion or heat pain. No differences between tPEMF and sham stimulation were observed for affect, motor, and cognitive outcomes. CONCLUSION: A single 30-minute tPEMF stimulation did not induce analgesic effects in neuropathic pain patients, compared to sham. Further study is needed to determine whether prolonged stimulation is necessary for analgesic effects.

Clinical- and Cost-Effectiveness of a Mandibular Advancement Device Versus Continuous Positive Airway Pressure in Moderate Obstructive Sleep Apnea.

STUDY OBJECTIVES: Limited evidence exists on the cost-effectiveness of mandibular advancement device (MAD) compared to continuous positive airway pressure (CPAP) therapy in moderate obstructive sleep apnea (OSA). Therefore, this study compares the clinical and cost-effectiveness of MAD therapy with CPAP therapy in moderate OSA. METHODS: In a multicentre randomized controlled trial, patients with an apnea-hypopnea index (AHI) of 15 to 30 events/h were randomized to either MAD or CPAP. Incremental cost-effectiveness and cost-utility ratios (ICER/ICUR, in terms of AHI reduction and quality-adjusted life-years [QALYs, based on the EuroQol Five-Dimension Quality of Life questionnaire]) were calculated after 12 months, all from a societal perspective. RESULTS: In the 85 randomized patients (n = 42 CPAP, n = 43 MAD), AHI reduction was significantly greater with CPAP (median reduction AHI 18.3 [14.8-22.6] events/h) than with MAD therapy (median reduction AHI 13.5 [8.5-18.4] events/h) after 12 months. Societal costs after 12 months were higher for MAD than for CPAP (mean difference €2.156). MAD was less cost-effective than CPAP after 12 months (ICER -€305 [-€3.003 to €1.572] per AHI point improvement). However, in terms of QALY, MAD performed better than CPAP after 12 months (€33.701 [-€191.106 to €562.271] per QALY gained). CONCLUSIONS: CPAP was more clinically effective (in terms of AHI reduction) and cost-effective than MAD. However, costs per QALY was better with MAD as compared to CPAP. Therefore, CPAP is the first-choice treatment option in moderate OSA and MAD may be a good alternative. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT01588275.

The treatment of sleep-related painful erections.

INTRODUCTION: As specialists in male genital problems, urologists and sexologists will most likely to be involved in the treatment of males presenting with sleep-related painful erections (SRPEs). This means that this phenomenon needs to be recognized by urologists and sexologists, and that they should have knowledge of the current diagnostic and therapeutic approaches. Aim. To review the literature on SRPE and to find the best pharmacological treatment. Methods. Four personal clinical observations from two clinics and 29 other cases with SRPE found in PubMed were analyzed, especially regarding the results of pharmacological treatment. MAIN OUTCOME MEASURES: The results of pharmacological treatment. RESULTS: Many of the various treatments proved to be ineffective and only a few showed efficacy for a few weeks or months. The only effective drugs in the long term were baclofen, clonazepam, and clozapine. CONCLUSIONS: Until now, the phenomenon of SRPE is not well understood. The rarity of the published cases undoubtedly does not reflect the actual occurrence of SRPE. Controlled double-blind pharmacological trials are needed, and long-term follow-up including polysomnography coupled with nocturnal penile tumescence and rigidity monitoring may provide further information about SRPE.

Quantifying interhemispheric symmetry of somatosensory evoked potentials with the intraclass correlation coefficient.

Although large intersubject variability is reported for cortical somatosensory evoked potentials (SEPs), variability between hemispheres within one subject is thought to be small. Therefore, interhemispheric comparison of SEP waveforms might be clinically useful to detect unilateral abnormalities in cortical sensory processing. We developed and evaluated a new technique to quantify interhemispheric SEP symmetry that uses a time interval including multiple SEP components, measures similarity of SEP waveforms between both hemispheres and results in high symmetry values even in the presence of small interhemispheric anatomic differences. Median nerve SEPs were recorded in 50 healthy subjects (20-70 years) using 128-channel EEG. Symmetry was quantified by the intraclass correlation coefficient and correlation coefficient between global field power of left and right median nerve SEPs. In 74% of subjects left-right intraclass correlation coefficient was higher than 0.60, implying high SEP hemispheric symmetry in terms of shape and amplitude. Left-right intraclass correlation coefficients lower than 0.60 were due to differences in amplitude, unilateral absence of peaks, or shape differences. We quantified SEP waveform interhemispheric symmetry and found it to be high in most healthy subjects. This technique may therefore be useful for detection of unilateral abnormalities in cortical sensory processing.

Trismus as manifestation of bilateral internal capsule genu infarction.

Acute trismus can have different causes. We describe the presentation, course and radiological findings of a 34-year-old man who developed acute trismus and MRI findings consistent with the combination of an old and fresh infarction in the genu of the internal capsule. We believe it is important to consider stroke as a cause of acute trismus.

Five-year follow-up of a cordotomy.

Percutaneous cervical cordotomy is an invasive procedure to treat severe, opioid-resistant cancer pain. It is usually proposed for patients with a limited life expectancy. As a consequence, objective quantification of the long-term effects of this procedure is lacking. The present report describes a patient who was treated with a right-sided percutaneous cervical cordotomy for refractory cancer pain. Afterward, disseminated seminoma was diagnosed, which was cured with chemotherapy. Five years after the procedure, a qualitative and quantitative evaluation of the long-term effects was performed. Sensory dysfunction was observed in the left side of the body, but no motor neuron or autonomic dysfunction was observed. The influence of these long-term effects on the patient's daily activities was limited.