The effect of pneumococcal conjugate vaccines on incidence and microbiology associated with complicated acute otitis media.

OBJECTIVES: The objectives of this study were to investigate the incidence of complicated acute otitis media (cAOM) as well as the associated microbiology before and after introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV-7 and -13), respectively. CAOM comprises "heavy" AOM (AOM demanding hospitalization), mastodismus (M) and acute mastoiditis (AM). METHODS: A retrospective cohort study of the incidence and microbiology associated with cAOM during the non-PCV era, the PCV-7 and 13 eras, respectively. Clinical and microbiological data were prospectively registered in a local database. The incidences of cAOM as well as the distribution of various bacterial strains in the three eras were compared. RESULTS: A total of 246 cases of cAOM (125 in the pre-vaccine period (2001-2006), 50 in the PCV-7 period (2007-2010) and 71 in the PCV-13 period (2011-2015)) were identified. The incidence of hAOM decreased by 62% in the PCV7-era but increased to almost pre-vaccine levels in the PCV-13 era. In the M + AM group, a decrease by almost 21% in the PCV7-era was found compared to the pre vaccine era, whereas the decrease was only 12% in the PCV13-era. The three most common findings in both hAOM and M + AM were Streptococcus pneumonia (SP), group A streptococcus (GAS) and "no growth". In the hAOM group, SP decreased from 38% in the pre-vaccine era to 31% in the PCV7-era and further to 16% in the PCV13-era. GAS decreased from 17% in the pre-vaccine era to 0% in the PCV7-era and 16% in the PCV13-era. The percentage of "no growth" increased from 12% to 38% and 44%, respectively. In the M + AM group, SP decreased to 10% in the PCV13-era compared with 44% in the pre-vaccine era and 41% in the PCV7-era. An increase in GAS from 15% in the pre-vaccine era and PCV7-era to 30% in the PCV13-era was observed. The "no growth" percentage increased from 13% in the pre-vaccine era to 26% in the PCV7-era and 33% in the PCV13-era. CONCLUSION: Introduction of PCV7 and PCV13 has been associated with an overall reduction of cAOM in Central Region Denmark. Pneumococci were still one of the two most common bacteria species related to cAOM though a decrease in pneumococci positive cases was observed. We found an increase in M + AM induced by GAS and a relatively large increase in "no growth", which might be caused by a more aggressive pre-hospital approach to treatment with antibiotics. Consequently, it is not evident whether the reduction of incidences is caused by the vaccines or a more aggressive antimicrobial attitude to manage AOM. The shift to GAS from SP is worrisome, and therefore continuous surveillance of the microbiology associated with AOM is warranted.

Employment status 1 year after out-of-hospital cardiac arrest in comatose patients treated with therapeutic hypothermia.

BACKGROUND: Therapeutic hypothermia for comatose survivors of out-of-hospital cardiac arrest (OHCA) has improved survival and neurologic outcome. This study focused on return to work 1 year after therapeutic hypothermia. METHODS: From June 2004 to June 2009, patients between 18 and 65 years of age with OHCA, who were treated with hypothermia from two regions, representing one third of the national population, were identified from the Danish National Patient Registry, and from hospital and ambulance records. The patients' employment status was obtained from the Danish Ministry of Employment. RESULTS: One hundred thirty-three comatose patients after OHCA treated with hypothermia were identified. One hundred and four (78%) patients were employed, or able to work, at the time of cardiac arrest. This particular group of patients showed significant lower in-hospital mortality compared to the group of patients who were not able to work before cardiac arrest; 13% vs. 48%, respectively (P < 0.001). The workable group had a lower Charlson comorbidity score (P = 0.004), a higher incidence of witnessed cardiac arrest (P = 0.004) and a higher incidence of shockable heart rhythm (P < 0.001). Eighty-seven patients (84%), who were able to work prior to cardiac arrest, survived, and 55 (65%) of these patients were employed or able to work at 1 year follow-up. CONCLUSION: The majority of patients employed, or able to work prior to OHCA, had returned to work at one year follow-up. Predictors of return to work in comatose patients treated with hypothermia have to be identified in a larger-scale study.

Poisson regression models outperform the geometrical model in estimating the peak-to-trough ratio of seasonal variation: a simulation study.

INTRODUCTION: Several statistical methods of assessing seasonal variation are available. Brookhart and Rothman [3] proposed a second-order moment-based estimator based on the geometrical model derived by Edwards [1], and reported that this estimator is superior in estimating the peak-to-trough ratio of seasonal variation compared with Edwards' estimator with respect to bias and mean squared error. Alternatively, seasonal variation may be modelled using a Poisson regression model, which provides flexibility in modelling the pattern of seasonal variation and adjustments for covariates. METHOD: Based on a Monte Carlo simulation study three estimators, one based on the geometrical model, and two based on log-linear Poisson regression models, were evaluated in regards to bias and standard deviation (SD). We evaluated the estimators on data simulated according to schemes varying in seasonal variation and presence of a secular trend. All methods and analyses in this paper are available in the R package Peak2Trough[13]. RESULTS: Applying a Poisson regression model resulted in lower absolute bias and SD for data simulated according to the corresponding model assumptions. Poisson regression models had lower bias and SD for data simulated to deviate from the corresponding model assumptions than the geometrical model. CONCLUSION: This simulation study encourages the use of Poisson regression models in estimating the peak-to-trough ratio of seasonal variation as opposed to the geometrical model.

Paediatric arterial ischaemic stroke and cerebral sinovenous thrombosis in Denmark 1994-2006: a nationwide population-based study.

AIM: To assess the incidence rates (IR), clinical characteristics, risk factors, treatment and outcomes of paediatric arterial ischaemic stroke (AIS) and cerebral sinovenous thrombosis (CSVT). METHODS: Using population-based, nationwide medical registries, we identified all patients aged 0-18 years at the time of hospitalization with first-ever AIS and/or CSVT in Denmark between 1994 and 2006. Medical records were retrieved and reviewed. RESULTS: We identified 211 patients with AIS and 40 patients with CSVT corresponding to IRs of 1.33 (95% CI 1.16-1.52) and 0.25 (95% CI 0.19-0.34) per 100,000 person-years, respectively. The IRs peaked in infancy (<1 year) for both AIS and CSVT with an additional peak among adolescents (15-18 years) for CSVT. The IR of AIS increased 3.9% per year (p=0.036), whereas no changes were found for CSVT. In total, 48.2% of the patients received antithrombotic treatment; no major complications were observed. All-cause and thrombosis-related 30-day case fatality ratios were 3.6% and 2.4%, respectively; neurological sequelae were found in 56.2% of patients. CONCLUSION: The IR of AIS was highest in infants and had increased with 3.9% annually during the observation period. The IR of CSVT had an additional peak in adolescence and remained unchanged over time.

Neuropsychological experiences in neurotraumatology.

My work in Neurotraumatology was initiated in 1961, when I as a neuropsychologist got a position in a neurosurgical University department. The tasks were to evaluate the mental state of patients, give advices to family members regarding the mental and social prognosis of the patients and to support nurses in the initial care of the patients. Initially the methods that were made use of were tests developed by the German neurologist Kurt Goldstein and traditional psychometric tests, but it was not until the theories of A. R. Luria and his investigation method were applied that a true position as a member of the treatment team was secured. Reading Luria's book "Higher Cortical Functions in Man" made me aware of his theories. The skill to perform the investigation was acquired during visits to Luria's laboratory at the Bourdenko Neurosurgical Institute in Moscow in the nineteen-seventies. Text and material to "Luria's Neuropsychological Investigation" was published in 1974. The early work was further stimulated by the development in the neurosciences regarding brain plasticity and brain repair and experiences from visits to rehabilitation centres in the US, Yehuda Ben-Yishay's center at New York Medical School, George Prigatano's centre at the time in Oklahoma, and Lance Trexler's center at Community Hospital, Indianapolis led in 1985 to the establishment of the first post acute rehabilitation center in Europe: the Center for Rehabilitation of Brain Injury (CRBI) at the University of Copenhagen, DK. The main program was a holistic day program, six hours a day for four months in accordance with the university semesters, and an eigth months follow-up. Groups of 15 persons started together, collaborating in smaller groups. The present director of the CRBI is neuropsychologist Frank Humle. A thorough follow-up of the patients' state and improvement through the course of treatment towards social integration, including getting back to work was performed, and studies have indicated that successful integration of the traumatized patient is possible, provided that an early intensive care is succeeded by a comprehensive, individualized post-acute rehabilitation program, of which follow-up is a part, all within the frame of multidisciplinary collaboration.

Quality of life in patients with traumatic brain injury-basic issues, assessment and recommendations.

INTRODUCTION: Traumatic brain injuries (TBI) are one of the most common consequences of traffic accidents. Patients with mild, moderate or severe brain injuries suffer from physical, cognitive, behavioral, emotional and social problems. Most of these problems have been a long standing focus amongst practitioners and researchers. Only recently a development has started that took interest in the quality of life outcome of TBI patients. The international members of this consensus meeting reviewed the literature on Quality of Life assessment after TBI and discussed the applicability of different measurements to this specific patient group. TIME POINTS: During the acute phase (T1; < 3 month after trauma) QoL it is difficult to assess due to the reduced consciousness of TBI patients. In the phase of rehabilitation (T2; < one year after trauma) and in the post-rehabilitation phase (T3) repeated assessment of QoL is recommended. INSTRUMENTS: Several generic and disease-specific instruments possibly relevant to TBI patients or specifically developed for this group were assessed according to the existing evidence in the literature. Criteria for the evaluation of these instruments were: feasibility, specificity, validity, comprehensiveness, international availability, existence of norms, and psychometric quality. The cognitive impairment and the existential dimension were not sufficiently considered in most of the reviewed instruments. GROUP CONSENSUS: The family's and relatives' view of the patient's QoL should not be used as a proxy but provides an additional source of information in the acute phase. At T2 and T3, assessment of the patient's quality of life should include a generic as well as a disease specific instrument. Among the generic instruments the SF-36, the EuroQol and the WHO-QoL should be considered. The literature about specific instruments for patients with TBI like the EBIC is scarce. Therefore, the group could hardly give an empirically based recommendation. The need for further investigation on QoL instruments in TBI patients is strongly emphasized.

Measurement of transcobalamin by ELISA.

BACKGROUND: Transcobalamin is essential for the cellular internalization of cobalamin. Methods to quantify the unsaturated protein are available, but few attempts have been made to develop methods to quantify the sum of unsaturated and cobalamin saturated transcobalamin. METHODS: gamma-Globulins from two polyclonal rabbit antibodies against recombinant human transcobalamin were used as capture and detection antibodies, and recombinant human transcobalamin was used as calibrator in an ELISA design. RESULTS: The ELISA is specific for transcobalamin and has a detection limit of <1.6 pmol/L. The imprecision (CV) is 4-6% for mean concentrations of 13-70 pmol/L. The central 95% interval for serum from healthy blood donors (n = 77) was approximately 600-1500 pmol/L and showed limited variation with age and sex. No correlation was observed between the marker of acute phase reaction, C-reactive protein, and transcobalamin in plasma. CONCLUSIONS: The ELISA measures total transcobalamin in serum and thus can be used for measurement of transcobalamin in patients treated with cobalamin.

Luria's neuropsychological evaluation in the nordic countries.

The publication of Luria's Neuropsychological Investigation (LNI) by Christensen in 1975 introduced Luria's evaluation procedures to worldwide neuropsychology. The LNI demonstrated the benefit of a thorough qualitative analysis of an individual patient's functioning as well as the usefulness of a comprehensive theory of brain functioning. This article reviews the experiences that led to the development of the LNI, discusses its use and extension in Scandinavian countries, and presents clinical and research applications of the LNI in diagnosis and rehabilitation. A series of case examples provides justification and validity for the continued use of the LNI and related procedures. Discussion of the advantages and disadvantages of the LNI and consideration of possible modifications of the procedures and interpretative methods provide the rationale for continued development of Luria's approach.

Sociological and cultural aspects in postacute neuropsychological rehabilitation.

Various forms of postacute brain injury rehabilitation programs exist. Comprehensive day treatment programs are the most holistic, being neuropsychological in orientation. The importance of developing a trusting relationship and the use of inventive techniques in the individualization of treatment within a holistic rehabilitation program will be described via a case presentation, stressing the sociocultural aspects of the individual as central to treatment.

Subjective experience in brain-injured patients and their close relatives: a European Brain Injury Questionnaire study.

Results are reported from an international project the aim of which has been to develop and validate a wide-ranging questionnaire suitable for administration to brain-injured patients and their relatives. A self-report questionnaire concerning subjective experience of cognitive, emotional and social difficulties (The European Brain Injury Questionnaire, EBIQ) was administered to a group of 905 brain-injured patients, and close relatives to these competed a parallel version of the questionnaire concerning the brain-injured person. The sample was drawn from seven European countries together with Brazil. The same questionnaire was also administered to a group of 203-non-brain-injured controls, similarly in self-report and relative-report versions. Scales relating to eight specific areas of functioning, together with a global scale, are derived from the questionnaire and their internal reliability was estimated in the present data. Analyses of the 63 items of the questionnaire showed consistently greater levels of problems for the brain-injured group, especially as indicated by relatives. This pattern was substantially replicated among the nine scales. The scales discriminated well between stroke patients and those who had suffered a traumatic brain injury. There was also a tendency for reported problems to be greater for patients who were surveyed later post-injury (> or = 19 months) rather than earlier. Comparison of sets of controls derived from two countries (France and Brazil) showed small but important differences. It is concluded that the questionnaire has an acceptable reliability and validity, but that it will be necessary to obtain culturally relevant non-brain-injured control data when employing it in different countries.

Neuropsychological characteristics of Huntington's disease carriers: a double blind study.

A cohort of 33 people at risk for Huntington's disease (HD), applying for genetic testing, were tested with a battery of neuropsychological tests covering attentional, visuospatial, learning, memory, and planning functions. A psychiatric rating scale, SCL-90R, was also applied, mainly as a control, since cognitive dysfunction could be ascribed to functional disorders as well as neurodegenerative processes. Self-rating did not indicate any psychiatric symptoms in carriers or non-carriers. However, significantly inferior cognitive functioning in the gene carriers was disclosed by the neuropsychological tests. Primarily, attentional, learning, and planning functions were affected. It is concluded that premorbid cognitive decline occurs in HD.

Neuropsychology in Denmark.

The origins and development of neuropsychology in Denmark are briefly overviewed, as are the education and training opportunities for Danish neuropsychologists. Areas of application and research are presented, and the role of the rehabilitation of brain injury is emphasized, with specific reference being made to the Center for the Rehabilitation of Brain Injury at Copenhagen University, wherein the rehabilitation program and pertinent research ensuing from the center is presented. Future trends in Danish neuropsychology are also considered.

Psychosocial rehabilitation of cranial trauma and stroke patients.

This paper presents the results of a longitudinal psychosocial study of 22 cranial trauma patients and 14 stroke patients from the time preceding injury (using retrospective data), through a 4-5 month intensive rehabilitation programme, to a follow-up 1 year after completion of the programme. Although the two groups of patients differed on several demographic and medical characteristics, essentially similar patterns for psychosocial decline following injury and improvement following rehabilitation could be observed. For both groups, the proportion in marital or cohabitational relationships returned to pre-injury levels, and for both groups the proportion requiring assistance in their living situation declined following rehabilitation, as did use of the health services. Virtually all patients in both groups had been in employment or undergoing education at the time of the injury, and although this percentage declined in practice to a small minority of both groups post-injury, there was a significant increase in the proportions working or in education following the rehabilitation programme. Similarly, the pattern of leisure-time activities in both groups declined post-injury and was restored following rehabilitation. Since both groups entered the programme at over 2.5 years post-injury, these generally encouraging results seem less likely to reflect spontaneous recovery than a beneficial effect of the programme itself.

Psychosocial outcome following individualized neuropsychological rehabilitation of brain damage.

At the center for Rehabilitation of Brain Damage, University of Copenhagen, 46 consecutively admitted brain-damaged patients with varying pathologies and who were on average 2.9 years post-injury were treated in a daily four-month rehabilitation program in groups of about 10, followed by a six-month period of contact varying according to individual needs. An evaluation of psychosocial outcome is presented. The results, based on comparisons between pre-, post-treatment and follow-up questionnaire data, show continuing functional improvements in the areas of family life and living conditions. Dependence on health services declined. Over 70% of the patients returned to either work, further education or voluntary work activities. For the whole group, leisure activities returned to the pre-injury level. Follow-up at about two years revealed continuing improvements in all areas, suggesting social readaptation to a degree above expectations as judged from the existing literature.

Outpatient management and outcome in relation to work in traumatic brain injury patients.

This paper reports on a holistic psychosocial rehabilitation program for post-acute brain-injury patients. Methods and rationale are described and follow-up data are reported on a group of patients with regard to return to employment or educational programs. The results generally give grounds for optimism concerning the effectiveness of psychosocial rehabilitation.

Peritoneal catheter tip location during non-complicated continuous ambulatory peritoneal dialysis.

In the present study, we evaluated the relationship between 1. the volume and rate of dialysis outflow and subsequent inflow, 2. the patient's impression of the location of the catheter tip and 3. the stability of the catheter tip location. Thirteen patients were studied on 2 random occasions (periods 1 and 2). Inflow (L/min) was significantly faster than outflow (p less than 0.05). No catheter tips were located in the far upper part of the abdomen. Outflow with the catheter tip located in the middle part of the abdomen was significantly lower than with the tip located in the inferior quadrants (p less than 0.02). Two patients were able to feel the catheter tip at Period 1, and 4 at Period 2, but only 1 patient was able to state the exact location identical to fluoroscopy. Ninety-two percent of the fluoroscopic evaluations showed catheter tips located in the same anatomical regions in upright as well as supine positions. If vertical "neighbour" anatomical regions were included in the evaluation of the catheter tip migrations, all catheter tips were located at the same or the vertical "neighbour" region in the 2 study periods.

Intra-abdominal location of peritoneal catheters during CAPD.

Thirteen patients were studied on two random occasions in order to evaluate the relationship between 1) volume and rate of dialysis outflow and the subsequent inflow, 2) patient's impression of the location of the catheter tip, and 3) stability of the catheter tip location. Outflow with the catheter tip located in the middle part of the abdomen was significantly lower than with the tip located in the inferior quadrants (p less than 0.02). No catheter tips were located in the far upper regions of the abdomen. Only one patient was able to state the exact location identical to fluoroscopy. 92% of the fluoroscopic evaluations showed that catheter tips were located in the same anatomical region in the upright as well as in the supine position. If vertical "neighbour" anatomical regions were included in the evaluation of the catheter tip migrations, all catheter tips were located in the same or the vertical "neighbour" region at the two study periods.