Benefit of sequential bilateral cochlear implantation in children between 5 to 18 years old: A prospective cohort study.

OBJECTIVE: To determine the benefit of sequential cochlear implantation after a long inter-implantation interval in children with bilateral deafness receiving their second implant between 5 and 18 years of age. STUDY DESIGN: Prospective cohort-study. SETTING: Tertiary multicenter. PATIENTS: 85 children with bilateral deafness and unilateral implantation receiving a contralateral cochlear implant at the age of 5 to 18 years. METHOD: The primary outcomes were speech recognition in quiet and noise (CVC) scores. The secondary outcomes were language outcomes and subjective hearing abilities, all measured before and 12 months after sequential bilateral cochlear implantation. Medians of the paired data were compared using the Wilcoxon signed-rank test. Univariable linear regression analyses was used to analyze associations between variables and performance outcomes. RESULTS: A significant benefit was found for speech recognition in quiet (96% [89-98] vs 91% [85-96]; p < 0.01) and noise (65% [57-75] vs 54% [47-71]; p = 0.01) in the bilateral CI condition compared to unilateral (n = 75, excluded 10 non-users). No benefit was seen for language outcomes. The subjective sound quality score was statistically significant higher in bilateral compared to the unilateral CI condition. Pre-operative residual hearing level in the ear of the second implant, the inter-implant interval and age at time of second implantation was not significantly associated with performance scores. CONCLUSION: After 12 months of use, sequential bilateral cochlear implantation showed improved speech perception in quiet and noise and improved subjective sound quality outcomes in children despite a great inter-implantation interval (median of 8 years [range 1-16 years]).

The impact of a history of child abuse on cognitive performance: a cross-sectional study in older patients with a depressive, anxiety, or somatic symptom disorder.

BACKGROUND: Child abuse is a major global burden with an enduring negative impact on mental and physical health. A history of child abuse is consistently associated with worse cognitive performance among adults; data in older age groups are inconclusive. Since affective symptoms and cognitive functioning are interrelated among older persons, a synergistic effect can be assumed in patients with affective symptoms who also have suffered from child abuse. This study examines the association between a history of child abuse and cognitive performance in such patients. METHODS: Cross-sectional data were collected from the 'Routine Outcome Monitoring for Geriatric Psychiatry & Science' project, including 179 older adults (age 60-88 years) with either a unipolar depressive, any anxiety, or somatic symptom disorder referred to specialized geriatric mental health care. A history of physical, sexual, and psychological abuse, and emotional neglect was assessed with a structured interview. Cognitive functioning was measured with three paper and pencils tests (10-words verbal memory test, Stroop Colour-Word test, Digit Span) and four tests from the computerized Cogstate Test Battery (Detection Test, Identification Test, One Card Learning Test, One Back Test). The association between a history of child abuse and cognitive performance was examined by multiple linear regression analyses adjusted for covariates. RESULTS: Principal component analyses of nine cognitive parameters revealed four cognitive domains, i.e., visual-verbal memory, psychomotor speed, working memory and interference control. A history of child abuse was not associated with any of these cognitive domains. However, when looking at the specific types of child abuse separately, a history of physical abuse and emotional neglect were associated with poorer interference control. A history of physical abuse was additionally associated with better visual-verbal memory. CONCLUSIONS: The association between a history of child abuse and cognitive performance differs between the different types of abuse. A history of physical abuse might particularly be a key determinant of cognitive performance in older adults with a depressive, anxiety, or somatic symptom disorder. Future studies on the impact of these disorders on the onset of dementia should take child abuse into account. TRIAL REGISTRATION: ROM-GPS is registered at the Dutch Trial Register ( NL6704 at www.trialregister.nl ).

Impact of childhood trauma on multidimensional frailty in older patients with a unipolar depressive-, anxiety- or somatic symptom disorder.

OBJECTIVES: Frailty marks an increased risk for adverse health outcomes. Since childhood trauma is associated with the onset of physical and mental health diseases during the lifespan, we examined the link between childhood trauma and multidimensional frailty. METHOD: A cross-sectional study embedded in a clinical cohort study (ROM-GPS) of older (≥60 years) patients (n=182) with a unipolar depressive-, anxiety- and/or somatic symptom disorder according to DSM-criteria referred to specialized geriatric mental health care. Frailty was assessed with the Tilburg Frailty Indicator (TFI), comprising a physical, psychological, and social dimension. Physical, sexual and psychological abuse and emotional neglect before the age of 16 years was measured with a structured interview. RESULTS: Of 182 patients, 103 (56.6%) had experienced any childhood trauma and 154 (84.6%) were frail (TFI sum score ≥5). Linear regression analyses, adjusted for lifestyle, psychological and physical-health factors, showed that the presence of any type of childhood trauma was not associated with the TFI sum score, however when considered separately, physical abuse was (ß=0.16, p=.037). Regarding the specific frailty dimensions, any childhood trauma was associated with social frailty (ß=0.18, p=.019), with emotional neglect as main contributor. CONCLUSION: These findings demonstrate a complex link between different types of childhood trauma and multidimensional frailty among older psychiatric patients. Regarding the three dimensions of frailty, social frailty seems most affected by childhood trauma. This may have been underestimated until now and should receive more attention in clinical care and future research.

Autophagy lipidation machinery regulates axonal microtubule dynamics but is dispensable for survival of mammalian neurons.

Neurons maintain axonal homeostasis via employing a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. Abnormal MT-based trafficking hallmarks the pathology of neurodegenerative diseases, but the exact mechanism regulating MT dynamics in axons remains enigmatic. Here we report on a regulation of MT dynamics by AuTophaGy(ATG)-related proteins, which previously have been linked to the autophagy pathway. We find that ATG proteins required for LC3 lipid conjugation are dispensable for survival of excitatory neurons and instead regulate MT stability via controlling the abundance of the MT-binding protein CLASP2. This function of ATGs is independent of their role in autophagy and requires the active zone protein ELKS1. Our results highlight a non-canonical role of ATG proteins in neurons and suggest that pharmacological activation of autophagy may not only promote the degradation of cytoplasmic material, but also impair axonal integrity via altering MT stability.

Efficacy and safety of medical cannabinoids in older subjects: a systematic review.

This systematic review aims to integrate the evidence on indications, efficacy, safety and pharmacokinetics of medical cannabinoids in older subjects. The literature search was conducted using PubMed, EMBASE, CINAHL and Cochrane Library. We selected controlled trials including solely older subjects (≥65 years) or reporting data on older subgroups. 105 (74%) papers, on controlled intervention trials, reported the inclusion of older subjects. Five studies reported data on older persons separately. These were randomized controlled trials, including in total 267 participants (mean age 47-78 years). Interventions were oral tetrahydrocannabinol (THC) (n=3) and oral THC combined with cannabidiol (n=2). The studies showed no efficacy on dyskinesia, breathlessness and chemotherapy induced nausea and vomiting. Two studies showed that THC might be useful in treatment of anorexia and behavioral symptoms in dementia. Adverse events were more common during cannabinoid treatment compared to the control treatment, and were most frequently sedation like symptoms. Although trials studying medical cannabinoids included older subjects, there is a lack of evidence of its use specifically in older patients. Adequately powered trials are needed to assess the efficacy and safety of cannabinoids in older subjects, as the potential symptomatic benefit is especially attractive in this age group.

Rule based processing of the CD4000, CD3200 and CD Sapphire analyser output using the Cerner Discern Expert Module.

The latest version of our Laboratory Information System haematology laboratory expert system that handles the output of Abbott Cell-Dyn Sapphires, CD4000s and a CD3200 full blood count analyser in three high-volume haematology laboratories is described. The three hospital laboratories use Cerner Millennium Version 2007.02 software and the expert system uses Cerner Millennium Discern Expert rules and some small Cerner Command Language in-house programs. The entire expert system is totally integrated with the area-wide database and has been built and maintained by haematology staff members, as has the haematology database. Using patient demographic data, analyser numeric results, analyser error and morphology flags and previous results for the patient, this expert system decides whether to validate the main full blood count indices and white cell differential, or if the analyser results warrant further operator intervention/investigation before verifying, whether a blood film is required for microscopic review and if abnormal results require phoning to the staff treating the patient. The principles of this expert system can be generalized to different haematology analysers and haematology laboratories that have different workflows and different software.

A Dutch day treatment program for anorexia and bulimia nervosa in comparison with internationally described programs.

A Dutch day treatment program for patients with anorexia and bulimia nervosa is described and compared to intensive day treatment programs for patients with eating disorders outlined in international literature. The 5-day program is described in terms of its general characteristics, intended outcome and specific treatment interventions. Along these parameters it is compared to the programs found in a systematic literature search of day hospitalization programs for eating disorders. Global inspection shows a lot of similarities between all the programs. Looking more closely, also many important differences exist (concerning, e.g. treatment duration, intensity of treatment, theoretical orientation, goals of treatment and weight gain regime). Because of the differences, it is hard to compare outcome data between centres. Besides, on many of these dimensions, the literature does not yet tell us unambiguously what is best for our patients. Therefore, it is necessary to keep the dialogue between treatment centres going.

Source levels and harmonic content of whistles in white-beaked dolphins (Lagenorhynchus albirostris).

Recordings of white-beaked dolphin whistles were made in Faxafl6i Bay (Iceland) using a three-hydrophone towed linear array. Signals from the hydrophones were routed through an amplifier to a lunch box computer on board the boat and digitized using a sample rate of 125 kHz per channel. Using this method more than 5000 whistles were recorded. All recordings were made in sea states 0-1 (Beaufort scale). Dolphins were located in a 2D horizontal plane by using the difference of arrival time to the three hydrophones, and source levels were estimated from these positions using two different methods (I and II). Forty-three whistles gave a reliable location for the vocalizing dolphin when using method II and of these 12 when using method I. Source level estimates on the center hydrophone were higher using method I [average source level 148 (rms) +/- 12 dB, n = 36] than for method II [average source level 139 (rms) +/- 12 dB, n = 36]. Using these rms values the maximum possible communication range for whistling dolphins given the local ambient noise conditions was then estimated. The maximum range was 10.5 km for a dolphin whistle with the highest source level (167 dB) and about 140 m for a whistle with the lowest source level (118 dB). Only two of the 43 whistles contained an unequal number of harmonics recorded at the three hydrophones judging from the spectrograms. Such signals could be used to calculate the directionality of whistles, but more recordings are necessary to describe the directionality of white-beaked dolphin whistles.

Structural and mechanistic insights into the interaction between Rho and mammalian Dia.

Formins are involved in a variety of cellular processes that require the remodelling of the cytoskeleton. They contain formin homology domains FH1 and FH2, which initiate actin assembly. The Diaphanous-related formins form a subgroup that is characterized by an amino-terminal Rho GTPase-binding domain (GBD) and an FH3 domain, which bind somehow to the carboxy-terminal Diaphanous autoregulatory domain (DAD) to keep the protein in an inactive conformation. Upon binding of activated Rho proteins, the DAD is released and the ability of the formin to nucleate and elongate unbranched actin filaments is induced. Here we present the crystal structure of RhoC in complex with the regulatory N terminus of mammalian Diaphanous 1 (mDia1) containing the GBD/FH3 region, an all-helical structure with armadillo repeats. Rho uses its 'switch' regions for interacting with two subdomains of GBD/FH3. We show that the FH3 domain of mDia1 forms a stable dimer and we also identify the DAD-binding site. Although binding of Rho and DAD on the N-terminal fragment of mDia1 are mutually exclusive, their binding sites are only partially overlapping. On the basis of our results, we propose a structural model for the regulation of mDia1 by Rho and DAD.

One-hydrophone method of estimating distance and depth of phonating dolphins in shallow water.

Previous attempts at localizing cetaceans have generally used multiple hydrophone arrays and multichannel recording systems. In this paper, a low-budget localization technique using only one hydrophone is described. The time delays of the signals traveling via the surface and bottom reflection paths to the hydrophone, relative to the direct signal, are used to calculate the distance and the depth of a phonating animal. Only two additional measures, the depth of the bottom and hydrophone, have to be taken. The method requires relatively shallow waters and a flat bottom surface. Echolocating and burst pulsing Hawaiian spinner dolphins (Stenella longirostris) at the Waianae coast of Oahu, Hawaii, were localized over different bottom substrates. A tracking range of up to 100 m was achieved. The accuracy of the method is estimated by the total error differential technique. The relative distance estimation error is below 35% and the absolute depth error below 0.7 m, so that the location method is sufficiently precise for examining source levels in our study area. Because of its simplicity, the method ideally complements sound recordings and visual sightings of marine mammals and could lead to a better understanding of the nature and use of click trains by dolphins.

Health complaints and immunological markers of exposure to bioaerosols among biowaste collectors and compost workers.

OBJECTIVES: In a cross sectional study, work related health complaints and diseases of 58 compost workers and 53 biowaste collectors were investigated and compared with 40 control subjects. Levels of specific IgG antibodies to moulds and bacteria were measured as immunological markers of exposure to bioaerosols. METHODS: With a standardised protocol, the participants of the study were interviewed for work related symptoms, conditions of exposure to bioaerosols at their workplaces, exposure to bioaerosols from other sources, atopic diseases, and smoking habits. They were clinically examined by physicians specialised in occupational medicine. Also, concentrations of specific IgG antibodies against antigens of moulds and actinomycetes occurring regularly at these workplaces were measured and compared with the health complaints of the workers. RESULTS: Compost workers had significantly more symptoms and diseases of the airways (p=0.003) and the skin (p=0.02) than the control subjects. Health complaints of biowaste collectors did not differ significantly from those of the control group. Subjects with atopic diseases were underrepresented in the compost workers (p=0.003). Significantly increased antibody concentrations against fungi and actinomycetes were measured in workers at composting plants. The concentrations in biowaste collectors did not differ significantly from those in the control subjects. A significant association between the diseases and increased antibody concentrations were found in the compost workers. CONCLUSION: The high exposure to bioaerosols of compost workers is significantly associated with a higher frequency of health complaints and diseases as well as higher concentrations of specific antibodies against moulds and actinomycetes. A healthy worker effect is indicated by the underrepresentation of atopic diseases among the compost workers compared with biowaste collectors and the control group.

[Immunological reactions and health complaints in biological refuse personnel and composting by biological aerosol exposure]. / Immunologische Reaktionen und Gesundheitsbeschwerden bei Biomüllentsorgern und Kompostierern durch Bioaerosolexpositionen.

Employees in waste treatment industries are exposed to high levels of airborne microorganisms. Concentrations of 10(7) cfu/m3 air were measured in composting facilities, whereas exposures of bio-waste collectors were two orders of magnitude lower with exposure peaks up to 10(6) cfu/m3 air. These exposures were compared to specific antibody levels against molds and actinomycetes, work related health complaints, and diseases of the workers. 72 bio-waste collectors and 77 compost workers were examined and interviewed for work related symptoms, current occupational exposures, smoking habits, and exposures from other sources (farming, bird breeding, gardening) by physicians specialized in occupational medicine, using a standardized protocol. Levels of specific IgG antibodies to molds and actinomycetes occurring regularly at these workplaces were determined as biomarkers of exposure. The exposure data from the workplaces indicate a higher exposure of compost workers compared to bio-waste collectors. This corresponds with significantly increased health complaints of the upper airways and the skin and higher concentrations of specific antibodies against molds and actinomycetes in the compost workers. Atopic diseases were underrepresented in the compost workers compared to bio-waste collectors and population based data, indicating a healthy worker effect in this group. Occupational diseases from airborne microorganisms eligible for insurance compensation were observed in waste treatment facilities. More detailed studies are needed for exact assessment of health risks of workers in these industries.

Adverse effects in epilepsy therapy. Wait and see or go for it?

OBJECTIVES: Attention for adverse effects (AEs) is important for optimizing epilepsy treatment. However, a uniform strategy is lacking. In particular there appears to be a dichotomy between those who "wait and see" and those who "go for it", i.e. routinely check a list of AEs. Our intention is to identify the effects of different approaches. METHODS: Trial reports on carbamazepine or valproate monotherapy (Medline-search), and data from the Nijmegen Epilepsy Research Group were analyzed. RESULTS: Analysis suggests that for certain AEs, such as diplopia, dysarthria, affect and mood disturbances, headache, dizziness, gastro-intestinal disturbances, dermatological disturbances and idiosyncratic reactions, it does not matter which approach is chosen. However, sedation, cognitive impairments, sexual dysfunction, hair changes, nystagmus, gait disturbances, tremor and weight changes are reported more frequently when routinely checked. The value of routine laboratory monitoring is, however, questioned. CONCLUSIONS: Use of different strategies to detect AEs obstructs estimation of risks of AEDs. Baseline measurements and regular checking for those AEs, which are reported more frequently by authors who actively search for AEs, is advisable.

Use of antiepileptic drugs in a community-dwelling Dutch population.

We compared the treatment policy for patients with epilepsy in six Dutch cities, comprising 302, 149 inhabitants, with the treatment policies of a secondary referral center (a university hospital) and tertiary referral centers (outpatient departments of epilepsy centers). By comparing the prevalence of individuals receiving antiepileptic drugs in the six cities with the epidemiologic data for epilepsy in Rochester, Minnesota, we concluded that prescription data offer a suitable means by which to estimate the prevalence of epilepsy in a community. To compare prescriptions in cases of polytherapy, we normalized data by using defined daily doses published by the WHO Collaborating Center for Drugs Statistics Methodology and the Nordic Council on Medicines and concluded that the defined daily doses of antiepileptic drugs should be further elaborated. There is a need to obtain complete dose-response curves of equivalent antiepileptic drugs in humans. The trend of drugs use found in the six cities, the university hospital, and the epilepsy centers is, however, in accord with the expectations regarding primary, secondary, and tertiary referral centers.

Neither dosage nor serum levels of antiepileptic drugs are predictive for efficacy and adverse effects.

In order to assess whether doses or serum levels are predictive for the efficacy and adverse effects of antiepileptic drugs (AEDs), measures for exposure to drug combinations have to be used. For doses, the ratio of the observed prescribed daily dose (PDD) and the average defined daily dose (DDD) considered effective for the main indication of the drug was used. In analogy for serum levels, the OSL/ATL ratio, i.e. the ratio of the observed serum level and the average therapeutic level was used. In polypharmacy these ratios can be summed as the are normalized measures of strength. The correlations of these ratios with outcome measures were studied in 200 patients attending out-patient clinics of special centres for epilepsy; half of these patients were treated with monopharmacy and half with polypharmacy. As outcome measures the following indices were used: the index of seizures, which quantifies seizure type and frequency, the seizure activity index, the neurotoxicity score, the systemic toxicity score, and the composite index of impairments, which is the sum of the seizure activity index and the neurotoxicity score and the systemic toxicity score. When all data were pooled, the correlation coefficient between the PDD/DDD ratio and the OSL/ATL ratio was 0.77. However, when the data were examined separately for the monopharmacy and polypharmacy groups, the correlation was 0.31 for the monopharmacy group and 0.50 for the polypharmacy group. Neither the PDD/DDD ratio nor the OSL/ATL ratio correlated with the composite index of impairments or with any of the individual indices. Factors such as the difficulty of titrating the endpoint of seizure suppression and the development of tolerance to adverse drug effects may perhaps be responsible for these findings. This observational study signals the problem.

Patient-therapist interaction in the behavioral treatment of panic disorder with agoraphobia.

Although effective behavioral techniques have been developed, what aspects of the patient-therapist interaction affect treatment outcome remain largely unknown. This study hypothesized that the interaction between patient and therapist develops over several phases. Further, the association between behavior modes and treatment outcome was expected to alter as that interaction developed. Thirty patients diagnosed with panic disorder with agoraphobia were treated with a standardized behavioral treatment program of 12 sessions. The interpersonal verbal therapist and patient behavior modes were studied at Sessions 1, 3, and 10, using an observational instrument. It was found that behavior modes change over the course of treatment, in line with predictions derived from social-psychological models. The hypothesis that establishing a therapeutic relationship requires an empathic and nondirective stance by the therapist in Session 1 was partly confirmed.