Prediction of radiation-induced mucositis of H&N cancer patients based on a large patient cohort.

PURPOSE/OBJECTIVE: Radiation-induced mucositis is a severe acute side effect, which can jeopardize treatment compliance and cause weight loss during treatment. The study aimed to develop robust models to predict the risk of severe mucositis. MATERIALS/METHODS: Mucosal toxicity scores were prospectively recorded for 802 consecutive Head and Neck (H&N) cancer patients and dichotomised into non-severe event (grade 0-2) and severe event (grade 3+) groups. Two different model approaches were utilised to evaluate the robustness of the models. These used LASSO and Best Subset selection combined with 10-fold cross-validation performed on two-thirds of the patient cohort using principal component analysis of DVHs. The remaining one-third of the patients were used for validation. Model performance was tested through calibration plot and model performance metrics. RESULTS: The main predicted risk factors were treatment acceleration and the first two principal dose components, which reflect the mean dose and the balance between high and low doses to the oral cavity. For the LASSO model, gender and current smoker status were also included in the model. The AUC values of the two models on the validation cohort were 0.797 (95%CI: 0.741-0.857) and 0.808 (95%CI: 0.749-0.859), respectively. The two models predicted very similar risk values with an internal Pearson coefficient of 0.954, indicating their robustness. CONCLUSIONS: Robust prediction models of the risk of severe mucositis have been developed based on information from the entire dose distribution for a large cohort of patients consisting of all patients treated H&N for within our institution over a five year period.

Use of robot technology in passive mobilization of acute hospitalized geriatric medicine patients: a pilot test and feasibility study.

BACKGROUND: Along with an aging population, the field of robot technology in rehabilitation is expanding. As new technologies develop, it is important to test these clinically before implementation. To assess the possibilities of undertaking a future randomized controlled trial (RCT), the aim of this study was to pilot test and investigate the feasibility of a newly developed passive mobilization robot device in geriatric medicine patients. METHODS: We used a robot to perform passive mobilization for all recruited patients while they were lying in bed. Inclusion criteria include the following: ≥ 65 years of age, able to walk before hospitalization, and not capable of walking > 2 m at the first day of hospitalization. Exclusion criteria include the following: known moderate/severe dementia, unstable fractures (back, pelvis, or legs), high intracranial pressure, pressure ulcers/risk of developing pressure ulcers due to fragile skin, positive Confusion and Assessment Method (CAM) score, not able to understand Danish, and medical instability. A mixed-methods approach, including structured interviews for patients and relatives, questionnaires and semi-structured interviews for the staff, and observations in the clinic were used as data collection methods. A 6-week pilot test preceded the feasibility study to test study design, safety, interview guide, and setting, and to become familiar with the robot. RESULTS: The pilot test included 13 patients, made the staff confident in the use of the robot, and led to the correction of the interview guide. In the feasibility study, 177 patients were screened, 14 patients (four men, nine women) included, and 13 completed the intervention (median [IQR] age 86 [82-92] years). Overall, the robot was easy to use during passive mobilization and fully accepted by patients and relatives. Staff, however, found the robot difficult to maneuver. No adverse events were reported. CONCLUSIONS: Use of robot technology in passive mobilization of older patients was feasible and well accepted by patients, relatives, and staff. Technical and workflow-related issues, as well as the robot not performing active mobilization, affects the launch of a RCT and thereby its implementation in geriatric medicine patients.

Infection with Prevotella nigrescens induces TLR2 signalling and low levels of p65 mediated inflammation in Cystic Fibrosis bronchial epithelial cells.

Prevotella spp. are frequently identified in Cystic Fibrosis sputum. This study examined whether infection with Prevotella nigrescens, a frequently identified member of this species, contributes to inflammation in CF bronchial epithelial cells through activation of TLR- and NF-κB signalling pathways. CFBE41o- cells were infected with either P.nigrescens or Pseudomonas aeruginosa and incubated under anaerobic conditions for 4h. P.nigrescens activated TLR2 signalling but not TLR4 signalling while P.aeruginosa activated TLR4 signalling with a lesser effect on TLR2. P.aeruginosa induced significant IκBα phosphorylation 10min post infection with a return to control levels by 30min post infection. A significant induction in nuclear p65 DNA binding was observed at 2h post infection. In contrast, infection with P.nigrescens induced phosphorylation of IκBα 120min post infection, with significant induction in nuclear p65 DNA binding at 4h post infection only. Cytokine gene and protein responses were lower for P.nigrescens compared to P.aeruginosa. This study demonstrates the ability of a clinical P.nigrescens isolate to provoke a delayed NF-κB(p65) driven response through induction in TLR2 signalling and activation of sustained levels of IKKα.

Generic Dry-Contact Ear-EEG.

Generic dry-contact ear-EEG allows for discreet, user-friendly, unobtrusive, cost-effective and convenient recordings of EEG in real-life settings. In this study we introduce a new generic earpiece design with larger internal ear electrode distances, resulting in an increased spatial coverage compared to previous generic earpiece designs. The signal quality of ear-Fpz, within-ear (the measuring and reference electrode located in the same ear) and cross-ear (the measuring electrodes located in one ear and the reference electrode in the opposite ear) electrode configurations of the developed generic earpiece was evaluated with auditory steady-state responses (ASSR) and compared to dry-contact cEEGrid. Ten subjects with different ear sizes were included. The recordings were performed in a sleep setup, where the subjects were lying on a bed and the effect of sleeping position (back vs. sides) was investigated. We found that the generic earpiece attained statistically significant ASSRs with ear-Fpz, within-ear and cross-ear electrode configurations. However, the dry-contact cEEGrid achieved significantly higher average ASSR signal-to-noise ratio (SNR) compared to the generic earpiece. Additionally, this study showed no significant difference between back and side positions for the ear-EEG.

Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells.

BACKGROUND AND PURPOSE: NF-κB-driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA3 ) is a plant-derived diterpenoid with documented anti-inflammatory activity, which is reported to induce A20-like zinc finger proteins in plants. Here, we sought to investigate the anti-inflammatory effect of GA3 in airway epithelial cells and determine if the anti-inflammatory action relates to A20 induction. EXPERIMENTAL APPROACH: Primary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o-) were used. Cells were pre-incubated with GA3 , stimulated with Pseudomonas aeruginosa LPS; IL-6 and IL-8 release, A20, NF-κB and IκBα expression were then evaluated. To determine if any observed anti-inflammatory effect occurred via an A20-dependent mechanism, A20 was silenced using siRNA. KEY RESULTS: Cells pre-incubated with GA3 had significantly increased levels of A20 mRNA (4 h) and protein (24 h), resulting in a significant reduction in IL-6 and IL-8 release. This effect was mediated via reduced IκBα degradation and reduced NF-κB (p65) expression. Furthermore, the anti-inflammatory action of GA3 was abolished in A20-silenced cells. CONCLUSIONS AND IMPLICATIONS: We showed that A20 induction by GA3 attenuates inflammation in airway epithelial cells, at least in part through its effect on NF-κB and IκBα. GA3 or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction.

Distortion correction and calibration of intra-operative spine X-ray images using a constrained DLT algorithm.

This work presents an automatic method for distortion correction and calibration of intra-operative spine X-ray images, a fundamental step for the use of this modality in computer and robotic assisted surgeries. Our method is based on a prototype calibration drum, attached to the c-arm intensifier during the intervention. The projections of its embedded fiducial beads onto the X-ray images are segmented by the proposed method, which uses its calculated centroids to undo the distortion and, afterwards, calibrate the c-arm. For the latter purpose, we propose the use of a constrained version of the well known Direct Linear Transform (DLT) algorithm, reducing its degrees of freedom from 11 to 3. Experimental evaluation of our method is included in this work, showing that it is fast and more accurate than other existing methods. The low segmentation error level also ensures accurate calibration of the c-arm, with an expected error of 4% in the computation of its focal distance.

Family psychiatric morbidity of acute and transient psychotic disorders and their relationship to schizophrenia and bipolar disorder.

BACKGROUND: Although transient psychotic disorders are currently classified as a category separate from schizophrenia (SZ) and affective disorders, their distinctive features remain uncertain. This study examines the family psychiatric morbidity of the ICD-10 category of 'acute and transient psychotic disorders' (ATPDs), pointing out differences from SZ and bipolar disorder (BD). METHOD: From a cohort of 2.5 million persons, we identified all patients enrolled in the Danish Psychiatric Register who were ever admitted with ATPDs (n=2537), SZ (n = 10639) and BD disorder (n=5292) between 1996 and 2008. The relative risk (RR) of ATPDs, SZ and BD associated with psychiatric morbidity in first-degree relatives (FDRs) was calculated as the incidence rate ratio using Poisson regression. RESULTS: The RR of ATPDs [1.93, 95% confidence interval (CI) 1.76-2.11] was higher if patients with ATPDs had at least one FDR admitted with any mental disorder than patients without family psychiatric antecedents. An additional risk arose if they had FDRs admitted not only with ATPDs (RR 1.60, 95% CI 1.33-1.92) but also with SZ (RR 2.06, 95% CI 1.70-2.50) and/or BD (RR 1.55, 95% CI 1.23-1.96). Despite some overlap, the risk of SZ (RR 2.80, 95% CI 2.58-3.04) and BD (RR 3.68, 95% CI 3.29-4.12) was markedly higher if patients with SZ and BD had FDRs admitted with the same condition. CONCLUSIONS: These findings suggest that family psychiatric predisposition has a relatively modest impact on ATPDs and argue against a sharp differentiation of ATPDs from SZ and BD.

Excess mortality of acute and transient psychotic disorders: comparison with bipolar affective disorder and schizophrenia.

OBJECTIVE: To investigate mortality and causes of death of short-lived psychotic disorders, by carrying out a comparison with bipolar disorder and schizophrenia. METHOD: Record linkage study to the official register of causes of death of all cases aged 15-64 years who were listed for the first time in the Danish Psychiatric Register between 1995 and 2008 with an ICD-10 diagnosis of 'acute and transient psychotic disorders' (ATPDs; n = 4157), bipolar disorder (n = 3200) and schizophrenia (n = 4576). RESULTS: A total of 232 patients (5.6%) with ATPDs, 172 (5.4%) with bipolar disorder and 233 (5.1%) with schizophrenia had died over a mean follow-up period of 6.6 years. The standardized mortality ratio for all causes, natural causes and unnatural causes was significantly high for the three conditions. Mortality of ATPDs was greater in men, with about two-thirds of all deaths resulting from natural causes mainly cardiovascular, digestive, neoplastic and respiratory diseases. Suicide was the major cause of premature death in patients with ATPDs. CONCLUSION: These findings suggest that ATPDs are associated with an increased mortality from both natural causes and suicide.

Combined use of positron emission tomography and volume doubling time in lung cancer screening with low-dose CT scanning.

BACKGROUND: In lung cancer screening the ability to distinguish malignant from benign nodules is a key issue. This study evaluates the ability of positron emission tomography (PET) and volume doubling time (VDT) to discriminate between benign and malignant nodules. METHODS: From the Danish Lung Cancer Screening Trial, participants with indeterminate nodules who were referred for a 3-month rescan were investigated. Resected nodules and indolent nodules (ie, stable for at least 2 years) were included. Between the initial scan and the 3-month rescan, participants were referred for PET. Uptake on PET was categorised as most likely benign to malignant (grades I-IV). VDT was calculated from volume measurements on repeated CT scans using semiautomated pulmonary nodule evaluation software. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity and specificity of PET and VDT. RESULTS: A total of 54 nodules were included. The prevalence of lung cancer was 37%. In the multivariate model both PET (OR 2.63, p<0.01) and VDT (OR 2.69, p<0.01) were associated with lung cancer. The sensitivities and specificities of both PET and VDT were 71% and 91%, respectively. Cut-off points for malignancy were PET>II and VDT<1 year, respectively. Combining PET and VDT resulted in a sensitivity of 90% and a specificity of 82%; ROC cut-off point was either PET or VDT indicating malignancy. CONCLUSION: PET and VDT predict lung cancer independently of each other. The use of both PET and VDT in combination is recommended when screening for lung cancer with low-dose CT.

Do we agree about when patients are psychotic?

OBJECTIVE: To investigate into the use of the term 'psychotic' as defined by ICD-10 or by the concept of impaired reality testing, among psychiatric staff members. METHOD: Questionnaire investigation using 11 short case vignettes. RESULTS: Responses were received from 266 psychiatric staff members: psychiatrists, nursing staff and psychologists. When using ICD-10, patients were identified as psychotic with a sensitivity ranging from 90% to 55%. Specificity ranged from 60% to 75%. According to the concept of impaired reality testing, all three groups showed a sensitivity of about 60%, whereas specificity ranged from 65% to 50%. The combined use of the terms correlated significantly with responses regarding indication for legal detention for psychiatrists and nursing staff. CONCLUSION: In identifying a patient as 'psychotic' a broad concept of impaired reality testing was widely used particularly in cases with legal issues. Psychotic symptoms, however, were identified with high sensitivity and specificity.

Prediction of respiratory distress syndrome by the microbubble stability test on gastric aspirates in newborns of less than 32 weeks' gestation.

AIM: There is a need for a rapid method to identify infants who will develop respiratory distress syndrome (RDS) soon after birth, to allow early treatment of affected infants with surfactant. The microbubble stability test (MST) may be one such method, but clinical experience is sparse. METHODS: The MST was performed on gastric aspirates from 188 infants with a mean gestational age of 29 (range 23-31) wk. RESULTS: 87 infants developed moderate to severe RDS, corresponding to a prevalence of 46%. The sensitivity, specificity and predictive values for identification of infants with moderate to severe RDS were determined for the average diameter of bubbles, the proportion of microbubbles with different diameters and the total number of microbubbles. The proportion of microbubbles with diameters <20 or 25 microm gave the best prediction, with a sensitivity of 78-79%, a specificity of 57-58%, a positive predictive value of 62% and a negative predictive value of 76%. Early treatment with nasal continuous positive airway pressure probably mitigated the development of RDS in some infants with a low-degree surfactant deficiency and this may explain the relatively low specificity. CONCLUSION: In infants of <32 wk gestation RDS can be predicted by computerized image analysis of the size distribution of microbubbles generated in gastric aspirates.

Comparison of psychiatric ICD-10 diagnoses in Denmark and Germany.

A dataset of psychiatric ICD-10 diagnoses from the Danish case register concerning psychiatric hospitals was compared with a sample of psychiatric diagnoses from 27 psychiatric hospitals in Germany. The comparison shows a higher proportion of F1 diagnoses in the German dataset and a difference in the coding of alcohol dependence and harmful use. Some further differences in the groups F0-F6 are demonstrated and some of them are discussed. The most frequent diagnoses found in both datasets but in different sequence are alcohol dependence syndrome and paranoid schizophrenia and, in third place, adjustment disorder. Various aspects of the problem of rarely used diagnoses are discussed.

ICD-10 criteria for depression in general practice.

BACKGROUND: The rate of recognition of depressive disorder in general practice is reported to be low. Current classification systems, i.e. ICD-10 and DSM-III-R, and DSM-IV with operational diagnostic criteria, have led to greater agreement concerning the diagnosis of depressive disorder. The aim of this study was to assess the applicability and validity of the ICD-10 criteria for depression in general practice in Denmark. METHODS: After a 1-day training course in the ICD-10 criteria for depression, ten general practitioners, during an 8-week period assessed all patients aged 18 or older for depressive symptoms in accordance with the ICD-10 criteria. RESULTS: Among a total of 3505 consultations, 116 patients (3.3%) met the criteria for a depressive episode. Of these, 80 (68.8%) accepted to be reinterviewed by a psychiatrist, who confirmed the diagnosis of depressive disorder in 57 of the 80 patients (71.3%). LIMITATIONS: The number of 'false negative' cases are unknown in the study. CONCLUSION: The ICD-10 criteria for depression seem to be appropriate and valid in general practice.

Use of the ICD-10 classification in psychiatry: an international survey.

On the background of some years of experience with ICD-10 psychiatric diagnoses in many countries of the world, an international comparison was performed to evaluate the frequency and use of the ICD-10 psychiatric diagnoses. For future revision of the ICD-10, it is important to know which diagnostic categories are either not used or are used possibly in an unspecific manner. Nineteen departments of psychiatry in 10 different countries took part in the study, presenting data on 33,857 treatment cases leading to a total of 25,470 ICD-10 main diagnoses. The analysis of data reveals that on a four-character level (Fxx.x), the 10 most often used diagnostic categories represent 40% of all main diagnoses, and 70% on a three-character level (Fxx.-). There are 32 specific diagnostic categories on a four-character level which are not used at all and 121 which are used less frequently than 0.1% in inpatient and outpatient treatment. The study shows that the ICD-10 classification is in use in a variety of treatment settings worldwide. Further results and limitations of this study are discussed against the background of transcultural differences.

Psychoactive substance use diagnoses among psychiatric in-patients.

OBJECTIVE: To estimate the prevalence and possible under-diagnosing of substance use disorders and to consider factors that might influence diagnosing of substance use disorders. METHOD: Data collected from case records and PSE interviews of psychiatric in-patients from 12 psychiatric departments in Denmark admitted during October 1996 were compared with data from the Danish Psychiatric Register. RESULTS: A substantially lower prevalence of substance use diagnoses were found in the register (26.1%) than in the research data (50.0%). A high prevalence of co-occurrence between substance use disorders and mental disorders other than substance use disorders was found (37.3%). In the majority of cases knowledge of the substance use disorders was present in the case records, although they had not resulted in a diagnosis. CONCLUSION: The under-diagnosis of substance use disorders is due not only to concealed diagnostic signs and symptoms but also to an under-diagnosis by the psychiatrists, in spite of the fact that information on the substance use was accessible.

Reflections on the clinical utility of the ICD-10 and DSM-IV classifications and their diagnostic criteria.

OBJECTIVE: The change to non-theoretical, criteria-based diagnostic classification in ICD-10 and DSM-III/IV has presented a major innovation in clinical psychiatry. The aim of the present paper is to provide a provisional evaluation of their utility in clinical practice. METHOD: The method involved a close scrutiny of ICD-10 and DSM-IV with a view to identifying difficulties and problems in their use. RESULTS AND CONCLUSIONS: The criteria-based classifications are no longer just coding conventions, but have become part of the conceptual framework of the discipline itself. The advantages, particularly as to the quality and reliability of clinical diagnoses, outweigh the disadvantages with temptations to mechanistic and reductionistic applications of criteria and incomplete nosological evaluation. Comprehensive clinical evaluation, however, should work at two separate levels: one, the initial, syndromatical diagnostic level, followed by the other, the nosological level, with evaluation of factors possibly influencing course and outcome of the psychiatric disorders. Only when both the syndromatical diagnosis and nosological factors are taken into consideration, is it possible to get a full understanding of the disorder necessary for optimal treatment. In this way, clinical psychiatry can be kept as it was intended: a healing discipline.

Nasal continuous positive airway pressure and early surfactant therapy for respiratory distress syndrome in newborns of less than 30 weeks' gestation.

OBJECTIVE: To determine whether early versus late treatment with porcine surfactant (Curosurf) reduces the requirement of mechanical ventilation in very preterm infants primarily supported by nasal continuous positive airway pressure (nasal CPAP). DESIGN: Multicenter randomized, controlled trial. PATIENTS: The study population comprised 60 infants <30 weeks' gestation with respiratory distress syndrome (RDS) who had an arterial to alveolar oxygen tension ratio (a/APO2) of 0.35 to 0.22. The cohort from which the study population was generated comprised 397 infants. RESULTS: The need for mechanical ventilation or death within 7 days of age was reduced from 63% in the late-treated infants to 21% in early-treated infants. Increasing numbers of antenatal steroid doses also improved the outcome, especially in the early-treated infants. Six hours after randomization mean a/APO2 rose to 0.48 in the early-treated infants compared with 0.36 in the late-treated. The need of mechanical ventilation before discharge was reduced from 68% in the late-treated to 25% in the early-treated infants. CONCLUSIONS: Nasal CPAP in combination with early treatment with Curosurf significantly improves oxygenation and reduces the subsequent need for mechanical ventilation in infants <30 weeks' gestational age with RDS.