EAONO/JOS classification for acquired cholesteatoma: evaluating the impact of the number of affected sites on treatment and outcomes.

PURPOSE: The European and Japanese system for cholesteatoma classification proposed an anatomical differentiation in five sites. In stage I disease, one site would be affected and in stage II, two to five. We tested the significance of this differentiation by analyzing the influence of the number of affected sites on residual disease, hearing ability and surgical complexity. METHODS: Cases of acquired cholesteatoma treated at a single tertiary referral center between 2010-01-01 and 2019-07-31 were retrospectively analyzed. Residual disease was determined according to the system. The air-bone gap mean of 0.5, 1, 2, 3 kHz (ABG) and its change with surgery served as hearing outcome. The surgical complexity was estimated regarding the Wullstein's tympanoplasty classification and the procedure approach (transcanal, canal up/down). RESULTS: 513 ears (431 patients) were followed-up during 21.6 ± 21.5 months. 107 (20.9%) ears had one site affected, 130 (25.3%) two, 157 (30.6%) three, 72 (14.0%) four and 47 (9.2%) five. An increasing number of affected sites resulted in higher residual rates (9.4-21.3%, p = 0.008) and surgical complexity, as well poorer ABG (preoperative 14.1 to 25.3 dB, postoperative 11.3-16.8 dB, p < 0.001). These differences existed between the means of cases of stage I and II, but also when only considering ears with stage II classification. CONCLUSION: The data showed statistically significant differences when comparing the averages of ears with two to five affected sites, questioning the pertinence of the differentiation between stages I and II.

Potential of vermicomposting with mixtures of animal manure and vegetable leaves in the development of Eisenia foetida, microbial biomass, and enzymatic activity under semi-arid conditions.

Vermicomposting is the bio-oxidation and stabilization of organic matter involving relationships between the action of earthworms and microorganisms and the activation and dynamics of several enzyme activities. Semi-arid farmers to make (extra) money and organic production, produce their vermicompost using plant residues and animal manure, but there is no information about the final product generated. Thus, this study aimed to analyze the potential of vermicomposting with mixtures of animal manure and vegetable leaves in the development of Eisenia foetida, microbial biomass, and enzymatic activity in the semi-arid region, Brazil. The experimental design applied was randomized block in a 6 × 4 factorial scheme with four replicates, with six treatments (mixtures of cattle manure, goat manure, cashew leaves, and catanduva leaves) and evaluated at four-time intervals (30, 60, 90, and 120 days of vermicomposting). The treatments were placed in polyethylene pots in the same site, environmental conditions, and residues proportions as used by farmers. The characteristics analyzed were the number of earthworms (NE), total earthworm biomass (TEB) and earthworm multiplication index (MI), microbial biomass carbon (MBC), and activities of enzymes ß-glucosidase, dehydrogenase, alkaline and acid phosphatases. The cattle manure vermicomposted shows the highest average values observed for NE, MI, TEB, MBC, and enzymatic activity, regardless of the plant leaves mix. In general, the enzymes activities were found in the descending order of ß-glucosidase > alkaline phosphatase > dehydrogenase > acid phosphatase. The maturation dynamics of vermicompost were characterized by a decline in the microbial population and number and biomass of earthworms in the substrate and consequently a decrease in new enzyme synthesis and degradation of the remaining enzyme pool. Microbial biomass and enzymatic activity were indicators for changes in the quality of vermicompost.

Retronasal olfactory testing using candies sent by post and for screening purposes: a feasibility study.

BACKGROUND: The olfactory system is able to detect external odours through the orthonasal- and internal odours through the retronasal route. Flavour perception strongly relies on the sense of smell and this back route. In contrast to orthonasal, retronasal olfactory tests (ROT) are less frequently applied, although testing should be recommended for several reasons. The aim of the present investigation was to propose a suitable form of ROT for home-testing (and postal distribution) and evaluate a retronasal screening test. METHODOLOGY: Initially, 111 participants were tested using a 27-item version of the Candy Smell Test (CST). Fifty-four participants performed retesting, of which 25 subjects did so in a home-setting being supplied with professionally packed "candy-chains". Seven candies were chosen by means of hit rate differences in normosmics and severely hyposmics/anosmics. The 7-CST is designed in a non-forced-choice fashion with same seven flavours to choose from. RESULTS: For the 27-item CST both groups (subjects performing home-testing and those performing retesting at the clinic) showed highly significant test-rest-reliabilities. The 7-CST was capable of discriminating healthy from diseased subjects when being tested in 116 healthy subjects and 47 patients suffering from olfactory dysfunction. CONCLUSION: The CST is suitable for home-testing and postal distribution. The new 7-item CST can be valuable for rapidly revealing anosmics. These findings help in further standardizing ROT, may encourage rhinologists to more routinely evaluate retronasal olfactory abilities and pave the way for larger epidemiologic studies also in regard to food preferences and nutritional behaviour.

Testing gustatory function using either a forced-choice or a non-forced-choice paradigm - Does it make a difference?

BACKGROUND: Recently more interest is evolving for research on gustatory function, also due to findings of â€extraoral†taste receptors with postulated participation in a pathogen detection network. Also, bitter taste function seems to be reduced in patients with chronic rhinosinusitis. For testing gustatory function â€taste strips†(TS) have been validated in a forced-choice (fc) and a non-forced-choice (nfc) paradigm and used in several studies. Purpose of the investigation was to evaluate possible differences of named modalities. METHODOLOGY: Healthy subjects (n=102) with subjective normal gustatory function and patients (n=30) with potential taste dysfunction were included. All participants were tested twice (using TS in four concentrations of sweet, sour, salty, and bitter taste), either starting with a fc or a nfc paradigm. RESULTS: In tested patients there was a difference between fc and nfc procedure with higher results for bitter in the fc testing procedure, while other qualities did not differ. This effect was also visible in the overall participants with higher scores in the fc procedure for bitter taste. CONCLUSION: TS are valid to be used in a forced and a non-forced choice paradigm, with bitter taste showing slightly higher scores in forced-choice testing. Future investigators with focus on bitter taste perception should be particularly cautious when comparing results in regard to testing procedure.

From sweet to sweat: Hedonic olfactory range is impaired in Parkinson's disease.

INTRODUCTION: Olfactory dysfunction and neuropsychological symptoms like depression and anhedonia are common non-motor symptoms in Parkinson's disease (PD). The assessment of both functional domains includes clinical examination, olfactory testing, and standardized questionnaires. While olfaction is readily assessed by functional tests, the distinction of anhedonia as a separate symptom from other depressive symptoms is challenging. Thus, a test focusing on the assessment of hedonic olfaction may be helpful in the assessment of neuropsychological symptoms in PD. METHODS: We examined anhedonia by evaluating the perception of pleasantness of odors in PD patients (n = 57) and healthy controls (n = 46). Pleasantness of odors was registered on a visual 9-point scale. For the assessment of anhedonia we used the Snaith-Hamilton-Pleasure-Scale (SHAPS). Depression was evaluated with the Zung Self-Rating Depression Scale and the Beck Depression Inventory II. RESULTS: PD patients showed a substantial reduction in hedonic olfaction compared to controls (hedonic score: 1.5 vs. 2.2). Hyposmia, one of the most prevalent non-motor symptoms in PD, was a confounding factor. However, even normosmic PD patients showed a reduced hedonic olfaction compared to controls (hedonic score: 1.6 vs. 2.2). Furthermore, we observed a correlation between hedonic olfaction and the SHAPS-score for PD patients even though positive SHAPS-rating was observed in 9% of PD patients only, while no correlation to depression was present. CONCLUSION: These findings suggest that reduced hedonic olfaction might be an additional neuropsychological feature, probably giving insights into changes in hedonic tone complementary to hyposmia and depression in PD.

Acetaminophen/paracetamol: A history of errors, failures and false decisions.

Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed. Personal contacts existed to renowned researchers having contributed to the medical use of paracetamol and its precursors as H.U. Zollinger, S. Moeschlin, U. Dubach, J. Axelrod and others. Further information is found in earlier reviews by Eichengrün, Rodnan and Benedek, Sneader, Brune; comp. references. The history of the discovery of paracetamol starts with an error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side-effect 'epidemy' (phenacetin nephropathy, drug-induced interstitial nephritis) and ends with the discovery of second-generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child. It appears timely to reassess the risk/benefit ratio of this compound.

[Position paper "Chemosensory testing for expert opinion in smell disorders"]. / Positionspapier "Die chemosensorische Testung bei der gutachterlichen Abklärung von Riechstörungen"

Providing expert opinion in the context of smell disorders is often challenging, not only with regard to general aspects of providing an expert opinion but particularly with regard to chemosensory testing. Currently there is no consensus which chemosensory test should be selected and how they should be executed. This positions paper from Committee on Olfaction and Gustation of the German Society of Otorhinolaryngology, Head and Neck Surgery aims to give concrete recommendations for chemosensory testing for providing expert opinion for smell disorders with regard to the selection and execution of these test.

Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief.

OBJECTIVE: Administering cyclooxygenase-2 inhibitors preoperatively appears attractive since these drugs reduce post-operative pain, but do not increase the risk of post-operative bleeds, asthmatic attacks and stress-related gastrointestinal ulcers. In a former investigation, we could show that post-operative administration of etoricoxib reduces prostaglandin production in wound fluid, but the onset of action is variable due to delayed post-operative absorption. METHODS: In this study, we investigated the preoperative administration of etoricoxib in patients undergoing hip replacement. They received 120 mg etoricoxib or placebo 2 h before surgery and 1 day after in a double-blinded, randomized, parallel group design. RESULTS: A total of 11 patients were randomized (placebo n = 5; verum n = 6). We found high and constant levels of the drug in blood, central nervous system and wound fluid already at the end of surgery (t(max) < 2 h). This was accompanied by inhibition of prostaglandin production in the wound tissue (treatment p < 0.05), suppression of interleukin 6 increase in plasma (treatment p < 0.01), and - despite existing standard pain relief procedures - higher satisfaction with analgesics (time vs. treatment p < 0.05) and less demand for opioids (treatment p < 0.01) and intrathecal bupivacaine (treatment p = 0.05) administration. CONCLUSION: Administration of etoricoxib 2 h before surgery allows for an effective drug concentration in critical tissues, a reduction of the production of pro-inflammatory mediators and for better pain relief.

Thickness in entorhinal and subicular cortex predicts episodic memory decline in mild cognitive impairment.

Identifying subjects with mild cognitive impairment (MCI) most likely to decline in cognition over time is a major focus in Alzheimer's disease (AD) research. Neuroimaging biomarkers that predict decline would have great potential for increasing the efficacy of early intervention. In this study, we used high-resolution MRI, combined with a cortical unfolding technique to increase visibility of the convoluted medial temporal lobe (MTL), to assess whether gray matter thickness in subjects with MCI correlated to decline in cognition over two years. We found that thickness in the entorhinal (ERC) and subicular (Sub) cortices of MCI subjects at initial assessment correlated to change in memory encoding over two years (ERC: r = 0.34; P = .003) and Sub (r = 0.26; P = .011) but not delayed recall performance. Our findings suggest that aspects of memory performance may be differentially affected in the early stages of AD. Given the MTL's involvement in early stages of neurodegeneration in AD, clarifying the relationship of these brain regions and the link to resultant cognitive decline is critical in understanding disease progression.

What is setting the stage for abdominal obesity reduction? A comparison between personality and health-related social cognitions.

The present longitudinal study examines whether changes in waist circumference are best predicted by relatively stable and broad personality traits (dispositional optimism and pessimism), by modifiable and domain-specific social cognitions (health-related self-efficacy), or a combination of these. Altogether 385 participants (74% women; 50-65 years) attended the GOAL Implementation Trial, a lifestyle counseling intervention to improve diet and physical activity. Measurements were conducted prior to the intervention (Time 1), and 3 months (Time 2) and 12 months (Time 3) after Time 1. Three different models of the potential interplay between dispositional optimism and pessimism and health-related self-efficacy were tested. The analyses showed that the change in health-related self-efficacy during the intervention (Time 1-Time 2) was negatively related with waist circumference change between Time 1 and Time 3, indicating that increases in self-efficacy during the intervention resulted in reduction in waist circumference over 12 months. However, optimism and pessimism were unrelated to waist circumference change either directly or indirectly through changes in self-efficacy. Interventions enhancing participants' positive health-related expectancies such as self-efficacy are likely to be effective even when participants' dispositional expectancies are pessimistic.

[Cyclooxygenase inhibitors: adverse drug reactions are unavoidable, but only a few are (acutely) dangerous]. / Zyklooxygenasehemmer: Arzneimittelinteraktionen sind unvermeidlich, nur wenige sind (akut) gefährlich.

Non-steroidal, anti-inflammatory drugs are the most widely used remedies worldwide. Drug interactions are frequent, life threatening ones are rare: Bleeds on the basis of inhibition of platelet aggregation and loss of organ protection (GI-tract), thrombotic events due to loss of vasoprotection and increased propensity for blood coagulation (stroke), acute kidney failure on the basis of loss of kidney protection by prostaglandins together with stress to the organ and/or drugs interfering with the renal blood flow. Acute liver toxicity is typical for acetaminophen. Whether the risk is increased by other hepatotoxic drugs, as diclofenac, is uncertain at present. All risks can be reduced considerably by avoiding problematic drug interactions.

Quantitative assessment of gustatory function in a clinical context using impregnated "taste strips".

Assessment of gustatory sensitivity in a clinical setting is the prerequisite for correct diagnosis and adequate treatment of taste dysfunction. Despite of this, no taste test has been established for the routine clinical testing. The aim of the present study was to create a protocol which is easy to administer. The presently used technique is based on strips made from filter paper which were impregnated with different taste solutions (four concentrations each for sweet, sour, salty and bitter). These strips are placed on the tongue and subjects are asked to identify the taste quality. After establishing the concentration range of the taste solutions, the test was tried in 69 subjects. Each subject received eighteen taste strips (four concentrations of each taste quality plus two blanks) in a pseudo-randomized sequence. Results from this new procedure correlated significantly with the results of the well established extensive three-drop-technique (r69 = 0.67). Repeated measures indicated good reproducibility of the results for the taste strips (r69 = 0.68). These data suggest the usefulness of this new technique in routine clinical practice. Major advantages are long shelf-life, convenience of administration, short time needed for testing (approximately 8 min), and the possibility to test each side of the tongue separately.

Social-cognitive predictors of health behavior: action self-efficacy and coping self-efficacy.

The effects of social-cognitive variables on preventive nutrition and behavioral intentions were studied in 580 adults at 2 points in time. The authors hypothesized that optimistic self-beliefs operate in 2 phases and made a distinction between action self-efficacy (preintention) and coping self-efficacy (postintention). Risk perceptions, outcome expectancies, and action self-efficacy were specified as predictors of the intention at Wave 1. Behavioral intention and coping self-efficacy served as mediators linking the 3 predictors with low-fat and high-fiber dietary intake 6 months later at Wave 2. Covariance structure analysis yielded a good model fit for the total sample and 6 subsamples created by a median split of 3 moderators: gender, age, and body weight. Parameter estimates differed between samples; the importance of perceived self-efficacy increased with age and weight.

Specific sensory detection, discrimination, and hedonic estimation of nicotine enantiomers in smokers and nonsmokers: are there limitations in replacing the sensory components of nicotine?

The aim of this study was to investigate in smokers and nonsmokers (1) the olfactory and trigeminal detection of R(+)- and S(-)-nicotine and (2) the discrimination ability and hedonic estimation of nicotine enantiomers in olfactory and trigeminal concentrations. Thirty healthy male subjects (15 smokers, 15 nonsmokers) participated in the experiments. A randomized sequence of R(+)- and S(-)-nicotine stimuli (seven R(+)- and seven S(-)-nicotine stimuli) were introduced into the right nostril of the subjects using a Kobal-olfactometer. The subjects were instructed to group the stimuli into two categories (A and B). To test the role of the olfactory and the trigeminal system in this discrimination task, the authors studied the olfactory detection threshold for the "odorous" sensation and the trigeminal detection thresholds for the "burning" and "stinging" sensations. Nicotine enantiomers were presented at the individual "olfactory" and "trigeminal" concentration levels. The subjects estimated the hedonic properties using a bipolar visual analog scale (from "very unpleasant" to "very pleasant"). A statistical evaluation (t-test) revealed that the subjects were able to identify R(+)- and S(-)-nicotine at olfactory and trigeminal concentrations (p < or = 0.01, p < or = 0.001, respectively). At concentrations near the detection thresholds, i.e., clearly below subjective pain thresholds, smokers rated both nicotine stereoisomers to be significantly more pleasant than did nonsmokers (t-test, R(+)-nicotine: p < or = 0.05; S(-)-nicotine: p < or = 0.01). Increasing the concentrations to above trigeminal thresholds resulted in a difference in hedonic estimates. Smokers perceived the S(-)-isomer as being less unpleasant than nonsmokers at trigeminal concentrations (t-test, p < or = 0.001). This difference in perception might be explained by the smokers' experience with S(-)-nicotine, which is the natural nicotine enantiomer in tobacco.

Familial risk for alcoholism and self-reported psychopathology.

Three groups of young men varying in familial alcoholism risk (high density, high risk [HDHR]; low density, high risk [LDHR]; and low risk [LR]) were compared on the 11 clinical scales of the Personality Assessment Inventory. Significant group differences were found on 9 scales, with scores of the HDHR group exceeding those of the other 2 groups. No differences were found between the LDHR and LR groups. When the proportion with pathological scores per scale was examined, significant group differences were still revealed on 7 scales. The HDHR group exceeded the other 2 groups, but the LDHR group also exceeded the LR group on several scales. These findings support the need to more finely characterize familial alcoholism risk than is provided by the typical high-risk-low-risk dichotomy. Finally, statistically controlling for normal variations in response style reduced the number of group differences, although the same patterns persisted.

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p <0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p <0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.

Population pharmacokinetics of fast release oral diclofenac in healthy volunteers: relation to pharmacodynamics in an experimental pain model.

PURPOSE: Population pharmacokinetics of a fast release diclofenac were assessed with special focus on pharmacodynamic implications. METHODS: In a double blind four-way crossover study, 20 healthy volunteers received orally 50 and 100 mg diclofenac-Na effervescent ("fast-release NSAID"), 50 mg diclofenac tablets ("control"), or placebo. Population pharmacokinetics of the fast release diclofenac were assessed using a nonlinear mixed effects modeling approach (NON-MEM). Analgesic effects were investigated by means of an experimental pain model based on both pain-ratings and cortical evoked potentials after specific stimulation of nasal nociceptors with short pulses of gaseous CO2. RESULTS: Pharmacokinetics of fast release diclofenac were best described by a two-compartment population model, with an estimated terminal half-life of 1.2 hours. Pharmacokinetics of diclofenac tablets were highly variable and a population pharmacokinetic model could not be obtained. As an indication of an early onset of analgesic effects, 100 mg fast release diclofenac but not the tablets significantly reduced the amplitudes of pain-related evoked potentials at 30 min after administration. CONCLUSIONS: Earlier drug absorption and lower pharmacokinetic variability of the fast-release formulation are likely to be preserved in a population.