Back pain is one of the most frequent complaints in the nursing profession. Thus, the 12-month prevalence of pain in the lumbar spine in nursing staff is as high as 76%. Only a few representative studies have assessed the prevalence rates of back pain and its risk factors among nursing staff in nursing homes in comparison to staff in home-based care facilities. The present study accordingly investigates the prevalence in the lumbar and cervical spine and determines the physical workload to lifting and caring in geriatric care.1390 health care workers in nursing homes and home care participated in this cross sectional survey. The nursing staff members were examined by occupational physicians according to the principals of the multistep diagnosis of musculoskeletal disorders. Occupational exposure to daily care activities with patient transfers was measured by a standardised questionnaire. The lumbar load was calculated with the Mainz-Dortmund dose model. Information on ergonomic conditions were recorded from the management of the nursing homes. Comparisons of all outcome variables were made between both care settings.Complete documentation, including the findings from the occupational physicians and the questionnaire, was available for 41%. Staff in nursing homes had more often positive orthopaedic findings than staff in home care. At the same time the values calculated for lumbar load were found to be significant higher in staff in nursing homes than in home-based care: 45% vs. 6% were above the reference value. Nursing homes were well equipped with technical lifting aids, though their provision with assistive advices is unsatisfactory. Situation in home care seems worse, especially as the staff often has to get by without assistance.Future interventions should focus on counteracting work-related lumbar load among staff in nursing homes. Equipment and training in handling of assistive devices should be improved especially for staff working in home care. Back pain is one of the most frequent complaints in the population in industrialized countries - for example the 12-month prevalence of chronic back pain in Germany in 2003 was 16% in men and 22% in women . 57% of men and 66% of women reported that they had suffered from back pain (of any duration or intensity) within the previous 12 months [There is a growing number of older people in need of health care and services  and it iIn 2007, a total of 572,211 health care workers were active in geriatric care, of which 31% worked in home care facilities ,15. In sThe study was advertised in specialized journals, to enrol occupational physicians in the study. The interested physicians then encouraged the facilities to take part in the study. A total of 137 geriatric care facilities throughout Germany were contacted. 63% of these facilities took part in the study (68 nursing homes and 18 home care services). A total of 3390 health care workers were contacted in the participating facilities. Documents were returned by 2164 persons (64%). Complete documentation - including the findings from the occupational physicians and a questionnaire completed by the respondents - was available for 1390 persons (41%). Participation in the study was voluntary; all subjects gave informed written consent. The study was approved by the Hamburg Medical Council.Nursing staff was divided into three job categories: registered nurses  with an officially recognised diploma after a three-year training, nursing aides (including assistant nurses) with at least a one-year nursing training without examination, and nursing auxiliaries with less or no formal nursing training.41 occupational physicians performed the orthopaedic examination. They were given training by an orthopaedic specialist in the orthopaedic examination techniques, in order to standardise data collection. Data on the intensity of the back pain in the previous four weeks and on inability to work during the preceding 12 months were recorded by the physicians. The orthopaedic examination was based on the principles of the multistep diagnosis of musculoskeletal disorders (MSD) . This is[See additional file The study subjects had to complete a standardised questionnaire, giving information about sociodemographic and profession-related data , and the frequency of load related activities combined with patient transfers. Other components of the questionnaire were:• Work ability (WA): WA was estimated by the subjects using the Work Ability Index (WAI). For the present study, two dimensions of the WAI were selected, dimension 2 "WA with respect to the physical and psychological demands of the work" and dimension 7 "mental resources"). The values for the WAI dimensions were calculated according to standardised coding instructions ,23.• Pain intensity: Information was recorded on the intensity of the pain in the regions of the cervical and lumbar spines for the 4 weeks preceding the questionnaire. Pain intensity was described according to the Graded Chronic Pain Status (GCPS) on a 10-point scale . For the• History of back diseases: Earlier back diseases were registered by recording the utilisation of medical services because of back pain in the preceding 12 months. This included treatment in a rehabilitation program or an individual consultation with the occupational physician.Information on working conditions - such as the number of height adjustable patient beds, technical aids (like bath lifts and mobile lifter systems) and low tech ergonomic aids such as sliding sheets, transfer belts and anti-slip mats - were recorded from a telephone interview with the facility management.Body mass index (BMI) was calculated on the basis of self-reported data as the ratio of body weight (kg) to the square of the height (m), adjusted by a correction factor. The values for BMI were divided into three groups, <25 , 25 to <30 (overweight), and ≥30 (obese).The Mainz-Dortmund dose model (MDD) was used for the assessment of the lumbar load for care actvities with patient transfers ,27. Thisr: Lumbar disc compression force, MDD daily dose Di: Compression force on L5-S1 for single activity i (N)Fi: Duration of daily exposure to single activity i (h)tEach act of lifting was calculated with a loading duration of 7.5s. To assess the calculated lumbar disc compression forces, standard threshold values, namely 3.5 kNh for women and 5.5 kNh for men were used. It is assumed that the risk for back disorders is increased once these reference values are exceeded .To compare discrete variables - like orthopaedic findings and job related characteristics - between respondents in nursing homes and home-based care, chi-squared statistics were used, as well as analysis with the Mantel-Haenszel trend test where relevant. All continuous variables were assessed for normality using the Kolmogorov-Smirnov test. As no variable was normally distributed, the non-parametric Mann-Whitney test was used. All tests were applied two-tailed, and a significance level of 0.05 was chosen. Statistical analyses were performed using the SPSS version 14.0 for Windows.81% of the nursing staff were working in nursing homes with exclusive or predominant inpatient care and 19% in home care services. Of the nursing homes, about 50% had more than 100 patient beds, 30% between 70 and 100 beds and 20% fewer than 70 beds. The characteristics of the nursing staff for the two care settings are described in Table On the day of the examination, 18% of the staff in nursing homes complained of symptoms in the lumbar spine and 11% in the cervical spine Table . There wAbout 60% of nursing staff in both groups were given the more extensive tests in the complementary examination. Of the 13 orthopaedic findings in the lumbar spine, 10 were significantly more often abnormal in staff active in nursing homes than in home care . About 90% of the nursing staff reported that they either occasionally or almost always adjusted the height of the bed to their working procedures Table . Home-baTen of the twelve load related activities occurred significantly more often for staff in nursing homes, including activities such as changing the patient's position in the bed, shifting the patient up to the bed, and raising the patient from the lying position to sitting (data not shown). Calculation of the lumbar load showed that 90% of the female and 38% of the male staff were above the gender-specific reference values for the daily dose (no table). For 45% of the staff in nursing homes, the resulting lumbar load was found to be above the reference value of 5.5 kNh for men, in comparison to the figure of only 6.4% for staff in home care. The median lumbar load for staff in nursing homes was 5.4 kNh, in comparison to 3.5 kNh for home care staff Figure . There wMany studies on the situation in long-term health care have concentrated on geriatric care. In the present study, we have examined the prevalence of orthopaedic findings in the back and of the lumbar load for care activities in a group of 1390 health care workers in 86 nursing homes and home care facilities. Our results show that staff in nursing homes more often gave positive orthopaedic findings and more often complained of symptoms in the cervical spine. At the same time, staff in home-based care had a more favourable impression of the condition of their general health, their work ability in relation to the demands of the work and their mental resources than did their colleagues in nursing homes. This agrees with the study by Hasson and Arnetz, which found that home care staff experienced significantly less physical and emotional strain compared with staff in nursing homes . There hHeight adjustable patient beds and assistive devices can both be of great help in reducing lumbar load for care activities with patient transfer in geriatric care -35. NursAltering the height of patient bed to ergonomic lift level is supposed to be a technique to reduce the frequency and extent of marked inclination of the trunk  and was In our study, staff in nursing homes was exposed to a much higher lumbar load than staff in home care. Except for the study by Theilmeier et al. , which uThe validity of the reference values in the MDD procedure has currently been discussed in the field of occupational medicine  and modiCalculation of the lumbar load was based on self-reported data. Misclassification is therefore possible. Nevertheless, any masking of effects in the comparison between staff in nursing homes and home care should be negligible. Data on the implementation of back-protecting work practices are also self-reported data by the respondents. For this reason, bias from subjective estimation cannot be excluded.Staff in nursing homes reports more occupational exposure on the lumbar spine than home-based staff. Furthermore, staff in nursing homes had more abnormal orthopaedic findings, a higher lumbar load and reduced values for work ability. The present data therefore support the demand for consistent and vigorous implementation of preventive measures for staff in home-based care and - to a much greater extent - in nursing homes. It appears necessary to provide advanced training to support working procedures conducive to back health which should be specifically adapted to the differences between both care settings. Additional studies are needed for more verified information about the working conditions in home care setting.The authors declare that they have no competing interests.KK performed the statistical analyses, interpreted the data and drafted the manuscript. MD participated in the design of the study, interpreted the data and drafted the manuscript. AN participated in the design of the study and interpreted the data. BBB participated in the coordination of the study and helped to draft the manuscript. All authors read and approved the manuscript.Diagnostic procedure of orthopaedic examination. Scheme for the orthopaedic examination performed in this study according to Grifka [o Grifka .Click here for file


An 83-year-old woman presented with weakness in her right-hand and wrist extensors and swelling in the proximal part of the right forearm. Electromyography (EMG) confirmed involvement of posterior interosseous nerve at the level of proximal forearm. MR imaging demonstrated the characteristics of lipoma which extended on the anterolateral aspect of the right forearm and at the level of the radius neck. The lesion was parosteal lipoma causing compression and paralysis of the posterior interosseous nerve without sensory deficit. In this paper, posterior interosseous nerve palsy due to compression of a parosteal lipoma recovered after excision of the lipoma followed by intensive rehabilitation for six month. Surgical excision should be performed to ensure optimal recovery from the nerve paralysis. Lipomas are common benign soft-tissue tumours which are usually asymptomatic . SometimAn 83-year-old woman presented with acute and progressive weakness of the right-hand extensors with painless swelling in the proximal part of the right forearm. Interestingly, she noticed that weakness after a fall on the outstretched left hand leading to fracture of left distal radius. She was treated conservatively in a cast. Six weeks later, and during routine follow-up, she mentioned that she noticed her right-hand weakness only when she started to use it excessively. She denied any injury to her right-hand or elbow. Examination revealed a swelling 3 × 3 cm in the antero-lateral aspect of the right forearm in the region of supinator muscle. The swelling was soft in consistency and decreased in size on flexion with supination of the forearm indicating that the lump was deep to the brachioradialis muscle. Extension of the metacarpophalangeal joints of all fingers in her right-hand was weakened. Also, there was slight weakness in the wrist joint extension. There was no sensory deficit in any of the dermatomes of the hand or the forearm. Radiographs of the right elbow showed soft-tissue density closely related to the proximal radius with normal bone appearance. Electromyography of the posterior interosseous nerve and muscles demonstrated active denervation, but nevertheless there were 1 or 2 recruited motor units confirming continuity of these motor fibres. Magnetic resonance imaging (MRI) of the right forearm revealed a multilobulated mass with hypointensity signal on a T1-weighted sequence which is pathognomonic of a lipoma. The precise anatomical location was in the lateral and anterior aspects of the right radius neck and extending distally for about 3 cm as shown in Figures Postoperatively, with intensive physiotherapy, she noticed improvement in hand and wrist extension. The final check, 6 months later, confirmed that elbow, wrist, and hand function were similar in both sides.Compression or entrapment of the posterior interosseous nerve may occur at various anatomical sites in the forearm and for various reasons. At the level of proximal forearm, it can be caused by lipomas, fibromas, arteriovenous malformation, bursa, ganglion, or as a result of synovial cysts in osteoarthrosis or rheumatoid arthritis. In addition, focal constriction of the nerve may occur without trauma or external compression –8. Involvement of PIN by lipomas is unusual and is characterized by a gradual onset of symptoms without sensory loss , 9. The Parosteal lipoma often has distinctive features that allow diagnosis on radiographs. MR imaging is the procedure of choice following radiography because of its multiplan imaging capabilities and improved ability to show muscle atrophy caused by the compression of adjacent nerves. These factors have significant implication for improving preoperative assessment and for helping to guide surgical treatment. The classical finding of parosteal lipoma on plain radiographs is a radiolucent lesion in the soft tissue closely applied to the subjacent bone with or without some osseous changes . As in tSurgical excision of parosteal lipoma of the proximal radius has been recommended in the literature to prevent posterior interosseous nerve compression and to increase the likelihood of functional recovery as the recovery of the neurological deficit relates to the duration of symptoms. The prognosis after excision of parosteal lipoma is excellent, with very low recurrence rates , 13.In conclusion, parosteal lipoma occurring in the proximal radius may readily cause paralysis of the posterior interosseous nerve. Surgical excision might be required to prevent compression of the posterior interosseous nerve and facilitate neurological recovery.


Sternoclavicular septic arthritis is a rare condition and accounts only for 1% of cases of septic arthritis in the general population. The most common risk factors are intravenous drug use, central-line infection, distant-site infection, immunosuppression, trauma and diabetes mellitus. This is a report of an unusual case where this type of arthritis was masquerading as rupture of the cervical oesophagus.A 63-year-old man presented complaining of right neck pain and dysphagia following a bout of violent coughing. Physical examination revealed cellulitis extending from the right sternoclidomastoid region to the anterior upper chest. Computed tomography showed inflammatory changes behind the right sternoclavicular joint with mediastinitis and ipsilateral pleural effusion. These findings raised the suspicion of spontaneous rupture of the cervical oesophagus. Management involved jejunal feeding along with broad-spectrum antibiotics. The inflammation, however, relapsed after discontinuation of the antibiotics and this time, computed tomography pointed to a diagnosis of arthritis of the sternoclavicular joint. The patient responded completely to a 6-week course of oral penicillin, flucloxacillin and metronidazole.Sternoclavicular arthritis is a rare condition that has been associated with a variety of predisposing factors. It may, however, occur in otherwise completely healthy individuals and should be included in the differential diagnosis of other inflammatory conditions of the neck and upper chest. Sternoclavicular septic arthritis is a rare condition and accounts only for 1% of cases of septic arthritis in the general population .Due to the anatomical location of the infection, this entity can often mimic other inflammatory conditions of the neck and upper chest. This is a report of sternoclavicular arthritis in a previously healthy adult that was initially misdiagnosed and managed as possible spontaneous rupture of the cervical oesophagus.A 63-year-old Caucasian man presented complaining of right neck pain and dysphagia following a bout of violent coughing that he experienced on the previous day. On admission, he was haemodynamically normal with mild pyrexia. Physical examination revealed cellulitis extending from the right sternoclidomastoid region to the anterior upper chest with swelling and tenderness just above the right sternoclavicular joint. The blood tests showed leukocytosis and raised inflammatory markers. A plain chest X-ray showed a right pleural effusion. These findings raised suspicion of a spontaneous rupture of the cervical oesophagus. Oral intake was omitted and a nasojejunal tube was inserted for feeding along with empirical intravenous administration of penicillin, flucloxacillin and metronidazole. A computed tomography (CT) scan showed inflammatory changes behind the right sternoclavicular joint with small pockets of air behind the upper sternum, pleural thickening at the right apex with some adjacent lung consolidation and confirmed the presence of a pleural effusion Figures  and 2.A gastrografin swallow study showed a small irregularity of the lateral pharyngeal wall but not definitive contrast leak, and pharyngoscopy could not find any abnormality. Paracentesis of the sternoclavicular swelling was attempted under ultrasound guidance, but no micro-organisms were isolated from the aspirate. Nevertheless, because there was still a degree of uncertainty, it was decided to treat the condition with prolonged jejunal feeding and antibiotics. After 2 weeks on this regime, the inflammation resolved completely and the patient was allowed oral feeding and discharged home. However, 9 days after his discharge, the patient presented with the same symptoms. Another CT scan established the diagnosis of septic arthritis showing erosive changes within the right sternoclavicular joint Figure . The patInfection of the sternoclavicular joint is an uncommon entity often misdiagnosed at the first presentation. In 2004, Ross et al. published a comprehensive review of 180 cases [Staphylococcus aureus is responsible for the majority of the cases (49%), followed by Pseudomonas aeruginosa (10%), Brucella melitensis (9%), Escherichia coli (5%) and Mycobacterium tuberculosis (3%). Most cases of Pseudomonas pyarthrosis affecting the sternoclavicular joint have been reported in immunosuppressed intravenous drug users [Bacteria can easily pass from the subclavian vein into the joint space. This explains how a central-line insertion or drug injection directly into the jugular vein can cause the infection. For the same reason, a sternoclavicular infection can be secondary to a skin infection. Furthermore, various distant sites of infection have been described: urinary and respiratory tract infections, pericarditis and intra-abdominal abscess. rculosis %. Most cruginosa 0%, Brucehe cases 9%, folloThe classical clinical presentation of patients with septic sternoclavicular arthitis involves an insidious onset of chest pain localized to the sternoclavicular joint or pain referred to the ipsilateral shoulder or neck. Fever and leukocytosis are not invariably present. The median duration of symptoms at presentation is much longer than the typical septic arthritis of other joints. The majority of patients with this condition have a normal plain radiograph. The plain chest X-ray in our case showed contra-lateral deviation of the trachea and an ipsilateral pleural effusion. A CT scan showed inflammatory changes behind the right sternoclavicular joint, pockets of air behind the upper sternum, pleural thickening at the right apex with some adjacent lung consolidation. It also confirmed the tracheal deviation and the pleural effusion. CT scans show osteomyelitis in 69% of the reported cases, chest-wall abscess or phlegmon in 57%, joint space widening or fluid in 25% and mediastinitis in 20% [Our case raised the suspicion of oesophageal rupture mainly due to the history of violent cough and the anatomical distribution of the inflammation associated with mediastinitis and pleural effusion. In fact, forceful increase of the pharyngeal pressure may cause spontaneous rupture of the cervical oesophagus . The atyPrompt diagnosis and appropriate treatment with long-term antibiotics result in an excellent outcome in most cases. The choice of the broad-spectrum combination penicillin, flucloxacillin and metronidazole in our case was empirical, given that no risk factors for this condition were identified and no micro-organisms were isolated in the joint aspirate. Sternoclavicular septic arthritis may occasionally require operative treatment with resection of one half of the manubrium and the medial third of the clavicle. This may be indicated either when the arthritis involves extensive bony destruction or when conservative management is unsuccessful . OperatiAlthough rare, sternoclavicular arthritis can mimic other inflammatory conditions of the neck and upper chest due to the anatomical location of the infection and may be misdiagnosed, especially in patients without associated risk factors.CT: computed tomography.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.IEK conceived the idea, collected the patient's data and was the major contributor to the writing of the manuscript. MB did the literature search and drafted the manuscript. ND performed the CT examinations and JIL critically reviewed the paper. All authors read and approved the final manuscript.


Cigarette smoking has been implicated as an important risk factor for the development of respiratory symptoms in adults. The relationship of dyspnea with cigarette smoking has been examined in smokers and ex-smokers and the beneficial effects of smoking cessation have been demonstrated. Recent studies reported that in subjects who smoke cigarettes the risk of developing respiratory symptoms is higher in a dose-dependent way. Environmental tobacco smoke heavily influences the incidence of respiratory symptoms in both adults and in children. Up to the present time, the mechanisms whereby cigarette smoking causes dyspnea perception remain to be defined. Abnormalities in sensory nerves might diminish the perception of bronchoconstriction in smokers. In this regard, it has been postulated that prolonged exposure to cigarette smoke may lead to chronic depletion of sensory nerve neurotransmitters. Eosinophil airway inflammation has been proposed as a determinant of breathlessness via mechanisms affecting either the mechanical pathways that control breathlessness or the afferent nerves involved in perception of dyspnea. An increased number of eosinophils in some smokers implies the possibility that smoking may trigger immunological or other reactions associated with eosinophilia. In conclusion, cigarette smoking is by far one of the greatest risk factors for most respiratory symptoms, including dyspnea. Smoking is associated with the development of symptoms in a dose-dependent way and eosinophilia and airway hyperresponsiveness (AHR) increase the risk of developing dyspnea. The mechanisms responsible for inter-individual differences in dyspnea perception are difficult to clarify due to the wide variation in the perception of breathlessness present in normal subjects  in whom Cigarette smoking has been implicated as an important risk factor for the development of respiratory symptoms in adults . On this1, they have fewer symptoms than consistent smokers who reported more dyspnea at the last survey [Data were similar for male and female subjects. The results of the symptom-analysis of both the initial and last surveys would suggest that although restarters have the steepest rates of decline in FEVt survey . This mit survey . More ret survey   in smoking asthmatics [Neutrophilic airway inflammation and release of neutrophil chemoattractant cytokines, including IL-8, have been observed to be associated with smoke exposure, with sputum IL-8 concentration being related to percent-predicted forced expiratory volume in 1 second . Smoking cessation was shown to have a positive impact on growth of pulmonary function. Young smokers without respiratory symptoms experienced the same longitudinal changes in FEV1 as non-smokers [The presence of respiratory symptoms has been examined as a marker of susceptibility to the detrimental effect of smoking on respiratory function. In an analysis from the Tucson study of data on the growth of pulmonary function between 5.5 and 25 years of age, symptoms and smoking had a negative impact on growth of lung function, using FVC, FEVInterestingly, the habit of smoking may influence dyspnea perception also in fibrotic diseases. De Cremoux and colleagues  examinedIn summary, cigarette smoking is by far one of the greatest risk factors for most respiratory symptoms, including dyspnea. Smoking is associated with the development of symptoms in a dose-dependent way and eosinophilia and AHR increase the risk of developing dyspnea. In short, further studies are necessary in order to establish the exact interaction between cigarette smoking and airway inflammation with dyspnea perception.The authors declare that they have no competing interests.


One of the few in vivo studies which tested the hypothesis involved the examinationof the activity of aurothiomalate in the treatment of polyarthritis in Hooded Wistar rats. Activity ofaurothiomalate is only shown in animals which received thiocyanate. Hydrogen cyanide is aconstituent of cigarette smoke and the aurocyanide formed by the interaction with gold complexesand inhaled hydrogen cyanide rapidly diffuses into red blood cells. Because of the metabolism ofhydrogen cyanide to thiocyanate in the liver, there are higher plasma levels of thiocyanate insmokers than in non-smokers. Smokers may have a greater incidence of side effects than non-smokersbut there appears to be little difference in therapeutic response, possibly because there issufficient thiocyanate in extracellular fluid, even in non-smokers, to support the conversion of goldcomplexes to aurocyanide. The relationship between the metabolism and effects of the orallyactive gold complex, auranofin are less clear. Auranofin itself is taken up by cells with the loss of theligands bound to gold while its inhibitory activity against the oxidative burst of PMN decreases withincreasing cell density. For example, the lucigenin-dependent chemiluminescence of 106  PMN/mlis 46 percent of control at 0.5 μM auranofin but only 2.2 percent in 2.105  PMN/ml in the presenceof the same concentration of auranofin. A potentially active gold complex is a plasma componentwhich is taken up by red blood cells.Leads to the cellular effects of the anti-arthritic gold complexes may come from the determination of their metabolism by target cells and, possibly, cells in the immediateenvironment of the target cells. Polymorphonuclear leukocytes (PMN) and mononuclear cells(monocytes and lymphocytes) are present in inflamed joints of patients with rheumatoid arthritis andthese cells have been widely used in pharmacological studies on the gold complexes. It issuggested that the cellular effects of the gold complexes are mediated by the production ofaurocyanide. According to this hypothesis, PMN metabolize small quantities of thiocyanate tocyanide which, in turn, converts gold complexes, such as aurothiomalate, to aurocyanide(dicyanogold(I)) which inhibits the functions of PMN and other cells. There is now considerableevidence for this hypothesis from


Recent years have seen publication of a considerable number of clinical trials of preventive interventions against clinical malaria in children. There has been variability in the specification of end-points, case definitions, analysis methods and reporting and the relative lack of standardization complicates the ability to make comparative evaluations between trials.To prepare for a WHO consultation on design issues in malaria vaccine trials, controlled trials of preventive interventions against malaria in children in endemic countries were identified in which clinical malaria, or death, had been one of the main end-points. Trials were included that evaluated the impact of vaccines, insecticide-treated bed nets (ITN), intermittent presumptive or preventive therapy in infants (IPTi) or, in one instance, vitamin A supplementation. Methods that had been used in these trials were summarized and compared in order to identify issues that were directly relevant to the design of malaria vaccine trials.29 controlled trials of preventive malaria interventions were identified, of which eight were vaccine trials. Vaccine trials that were designed to detect an effect on clinical malaria all reported the incidence rate of first episodes of clinical malaria as their primary endpoint. Only one trial of a preventive intervention (of ITN) was identified that was designed to detect an effect on severe malaria. A group of larger trials were designed to detect an effect of impregnated bed nets or curtains on all-cause mortality as the primary end-point. Key methodological and reporting differences between trials are noted in the text. Two issues have been identified that are of some concern. Firstly, the choice of primary endpoint is not stated in the reports of a number of the trials and, secondly, the relationship between pre-specified analysis plans and trial reports is rarely made clear.This article reports an investigation into the ways in which trial design and reporting could be improved and standardized to enable comparative evaluation of the relative merits of malaria control measures, and specifically with respect to the design of malaria vaccine trials. The need for standardization of clinical trial design, conduct, analysis and reporting has been also affirmed as a priority area by the Malaria Vaccine Technology Roadmap. The development and deployment of new and improved intervention methods for malaria control shows promising signs of reducing significantly the global burden of malaria. However, the search for more effective control methods still has very high priority. Controlled trials remain essential for the rigorous assessment of the potential impact of new tools and strategies to reduce morbidity and mortality caused by malaria. In recent years, there have been a considerable number of randomized controlled trials of new malaria interventions directed at children, including trials evaluating candidate malaria vaccines, insecticide-treated bed nets (ITN) and intermittent presumptive or preventive therapy in infants (IPTi). The appropriate choices of the primary end-points in such trials and the measurement methods are prerequisites for the proper evaluation of the interventions. The end-points and measurement methods must allow comparability of the performance of the same intervention in different locations and age groups and over time at the same location. In addition, the comparability of performance of alternate control measures, or combinations of measures, relies on standardized methods of assessment.To prepare for a World Health Organization (WHO) consultation on design issues in malaria vaccine trials, the methods that have been used in reported malaria preventive intervention trials to estimate efficacy against clinical malaria and related end-points were reviewed and the strengths and weaknesses of the different approaches were summarized. The aim is to provide a resource for those planning clinical trials of preventive malaria interventions. The target audience is clinical trialists, statisticians and other technical personnel. A companion paper, resulting from a WHO consultation on the issues, was directed at policy makers, funders and regulators .Reports of trials published between 1990 and 2007 evaluating the impact of preventive malaria interventions were identified . Trial reports were found primarily through PubMed database searches. Papers were sought using the following search terms: malaria vaccin*, malaria vaccines [MeSH],  and (bednet or bed net or mosquito net or curtain), malaria ipti, malaria intermittent therapy infants, malaria presumptive therapy infants, malaria preventive therapy infants, malaria preventive clinical trial. Further trials were identified through the references of retrieved articles. In addition, investigators responsible for the design and analysis of clinical trials of preventive interventions against malaria were interviewed as part of a WHO consultation process on design of phase 3 trials of malaria vaccines. Each interviewee was asked to identify further eligible studies. Data on trial methods and reporting for each study were extracted into tables and are summarized [see additional file Papers were included if they reported randomized controlled trials of preventive malaria interventions with a primary or secondary objective stated as the estimation of efficacy against clinical malaria, severe malaria or all-cause mortality. Trials were excluded, to coincide with the intended scope of the review, if they were conducted in adult populations or in areas of unstable malaria transmission  or they did not report incidence end-points.29 randomized clinical trials of malaria preventive interventions in children published between 1990 and 2007 were identified, which reported estimation of efficacy against clinical malaria, severe malaria or all-cause mortality. Six trials, all of insecticide-treated bed nets or curtains, were cluster randomized. The other 23 were individually randomized.The trials could be classified broadly into two groups. The largest group consisted of trials designed primarily to detect an effect on clinical malaria. In some of these both clinical malaria and anaemia are described as efficacy measures in the same trial. In several trials, it was not possible to identify whether a single primary end-point had been specified amongst several end-points that were ostensibly reported as "co-primaries".The other group of trials, all of ITNs, were those designed to detect an effect on all-cause mortality. Severe malaria was a primary outcome measure in only one trial .All malaria vaccine trials -8 and seAn alternative end-point for trials designed to examine the overall impact against clinical malaria is the rate of all episodes of malaria. Only one trial was identified reporting multiple episodes of malaria as its primary end-point . For thiet al [Defining what constitutes an episode of clinical malaria is not straightforward in areas in which the disease is highly endemic. In such areas, at any one time, a significant proportion of children in a community may have malaria parasites in their blood. Many will be asymptomatic and others will have symptoms consistent with malaria. In some of this latter group the symptoms may be directly attributable to malaria but, because malaria symptoms are not specific to the illness, in others the symptoms may be due to another condition and the malaria parasites in their blood are merely coincidental. In general, the higher the blood parasite load, the more likely it is that the symptoms are due to malaria. Thus, in preventive trials, it is common practice to define clinical malaria as being present in those who have symptoms and signs consistent with malaria and who also have a density of parasites in their blood greater than some specified level. Choice of the appropriate minimal parasite density level (cut-off) for defining malaria will depend upon the endemicity of malaria in the study area. For example, in areas where malaria is relatively uncommon, the finding of any malaria parasites in the blood of someone presenting to a health facility with fever provides a sensitive and specific diagnosis of the disease. For malaria endemic areas, Smith et al  devised et al method, were presented in publications of intervention trials. This has generally not been done.In recent malaria vaccine trials in children, efficacy estimates using different parasite density cut-offs, in the same trial, have been presented. Case definitions with lower specificity (lower parasite cut-off levels) should theoretically yield lower point estimates of efficacy. Curiously, this expected effect has not been seen generally in the trials reviewed. Further research into this issue is warranted. Also, it would aid interpretation if the sensitivities and specificities of the various case definitions and parasite density cut-offs used, as derived by the Smith A different approach to defining clinical malaria was used in an ITN trial performed in Côte d'Ivoire . In thisAnother measure of clinical malaria was used in a trial of intermittent preventive therapy with sulphadoxine/pyrimethamine (SP) and iron supplementation performed in Kenya. The anaIn trials of malaria vaccines, an assessment has commonly been made of the effect of the vaccine on the incidence of parasitaemia as well as on clinical malaria. The former has been measured by taking repeated blood smears from some children following vaccination. In order to be able to measure new infections, in most trials, anti-malarial treatment has been given prior to vaccination to clear asexual parasitaemia. Thus, in five out of eight malaria vaccine efficacy trials in children, participants were treated for malaria at the start of the trial. A sixth trial used amodiaquine/SP pre-treatment in a separate cohort, where only anti-infection efficacy data was generated. In one et al [All malaria vaccine trials in children published to date have included some form of active case detection (ACD) for at least some trial participants. Two trials ,7 used aThe criteria used to trigger the taking of a blood smear to assess for a possible clinical malaria episode varied from trial to trial. This also affects interpretation of efficacy results. Thus, the results of trials must be interpreted in the light of the case detection systems used.In some trials, both ACD and PCD were used to detect clinical malaria cases and efficacy results were reported for cases detected by each of these methods. With suThere are three methods for calculating parasite density that have been employed in published intervention trials. Firstly, reading 100 or 200 high power fields, with the assumption that the volume of each high power field is 1/500 μl. Secondly, an assumption that the total white cell count is 8,000/μl and reading to 200 white blood cells. Thirdly, a calculation of white cell count individually and then reading to 200 WBC, with adjustment using the calculated count. It is difficult to compare the results of studies in which different counting methods have been used. Standardization on one method is desirable for accuracy, precision and to aid comparisons of the results in different trials and is essential for a multi-site licensure trial. Double reading of all blood smears for efficacy end-points is also undertaken, and is highly desirable, in most intervention trials. The elements of slide taking and reading that require standardization include: staining of blood smears including where Field's stain and Giemsa stain are used; procedure for double and third reading of smears; internal quality control (QC) procedures; external QC of a proportion of blood smears and the process for resolution of discrepancies found through external QC.While clinical malaria has been the primary end-point in most studies of preventive interventions studies, some studies have measured the impact on more severe disease or death and others have evaluated the impact on hospital utilization for any cause.Whilst the presenting features and, to some extent, predictors of mortality in hospitalized cases of malaria have been adequately described in a handful of settings in sub-Saharan Africa -40, onlyIn some trials an attempt has been made to estimate the extent to which a preventive malaria intervention has reduced the overall burden of illness on the health service, such as the impact on all-cause clinic or hospital attendance. For example, this measure was included in the evaluation of the Asembo/Gem Kenyan ITN trial . Over 20A relatively large number of possible efficacy end-points are potentially available to malaria investigators and malaria preventive intervention trials may be particularly vulnerable to the multiple comparisons problems in trial design. Many of the trials reviewed reported a large number of different efficacy end-points . Furthermore, it is not generally made clear in papers how many efficacy end-points were analysed but were not reported. A ranking of end-points pre-unblinding, in the analytic plan, with publication in the pre-specified rank order would be one way to address concerns about multiple comparisons. Conservative methods such as adjusting significance levels for the number of end-points examined have not been used in trials reported to date. In practice, in addition to the primary end-point (if one is specified!) the sum of the evidence from all of the end-points measured is usually taken into account, together with their biological plausibility and their consistency, in the overall assessment of the potential impact of an intervention. Assessment would be aided if, for all trials, the reporting and analysis plans were made available for review together with the trial protocol.There is a wealth of data available from randomized controlled trials of malaria preventive interventions directed at children, much published in recent years. Further information will become available through ongoing iPTi trials and the planned large multi-site phase 3 trial of the GlaxoSmithKline/Malaria Vaccine Initiative vaccine candidate RTS, S. Attention to the design issues identified above will aid the generation of data that can inform public health decisions.It is notable that many of the trials identified in this review report the incidence rate of first episodes of clinical malaria as the primary endpoint. Given the public health interest in a potential new intervention's impact on the community burden of clinical malaria, further attention to analysis methods for the incidence rate of all episodes of malaria appears to be one priority for those undertaking clinical trials in this field. This may help bridge the gap between proof-of-concept and evaluation of public health benefit for preventive interventions against clinical malaria.An ambitious, but highly laudable goal, stated as a priority area in the strategic framework of the Malaria Vaccine Technology Roadmap, is clinThe authors declare that they have no competing interests.VSM performed the literature search, extracted the data on methods and reporting and wrote the first draft of the manuscript. ZR conceived the scope for the review and provided input into the final manuscript. PS provided input and review into the final manuscript.Tables 1–4. Tables summarising methods and reporting for identified randomized controlled trials of preventive malaria interventions.Click here for file


EPEATMASKER. Sequences annotated by REPEATMASKER often correspond to fragments of repetitive elements resulting from the insertion of younger elements or other rearrangements. Although REPEATMASKER annotation is indispensable for studying genome biology, this annotation does not contain much information on the common origin of fossil fragments that share an insertion event, especially where clusters of nested insertions of repetitive elements have occurred.Dispersed repeats are a major component of eukaryotic genomes and drivers of genome evolution. Annotation of DNA sequences homologous to known repetitive elements has been mainly performed with the program RANNOTATE, a computational tool to process REPEATMASKER annotation for automated i) defragmentation of dispersed repetitive elements, ii) resolution of the temporal order of insertions in clusters of nested elements, and iii) estimating the age of the elements, if they have long terminal repeats. I have re-annotated the repetitive content of human chromosomes, providing evidence for a recent expansion of satellite repeats on the Y chromosome and, from the retroviral age distribution, for a higher rate of evolution on the Y relative to autosomes.Here I present REANNOTATE is ready to process existing annotation for automated evolutionary analysis of all types of complex repeats in any genome. The tool is freely available under the GPL at .RE Repeats of high sequence complexity – mostly transposable elements (TEs) – account for a large portion of many eukaryotic genomes. In humans they comprise almost half of the  genome , and in EPEATMASKER and wheat [GENBANK:AF459639.1] sequences were annotated with REPEATMASKER using a cutoff score of 200. Maize repeat sequences in the REPBASE UPDATE. This is the main repeat re-annotation file output by REANNOTATE as a tab delimited text file. Each line corresponds to a repetitive element model.Click here for fileDescription of data fields in the main re-annotation file. Data fields in Additional file Click here for fileANNOTATE.RE Current version of REANNOTATE.Click here for fileANNOTATE user manual.RE User manual.Click here for file


This systematic review aimed to evaluate the psychometric properties and clinical utility of all condition specific outcome measures used to assess quality of life (QOL) in school aged children with cerebral palsy (CP).Relevant outcome measures were identified by searching 8 electronic databases, supplemented by citation tracking. Two independent reviewers completed data extraction and analysis of the measures using a modified version of the CanChild Outcome Measures Rating Form.From the 776 papers identified 5 outcome measures met the inclusion criteria: the Care and Comfort Hypertonicity Questionnaire (C&CHQ), the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD), CP QOL-Child, DISABKIDS and PedsQL 3.0 CP Module. There was evidence of construct validity for all five measures. Content validity was reported for all measures except PedsQL 3.0. The CPCHILD and CP QOL-Child were the only outcome measures to have reported data on concurrent validity. All measures, with the exception of one (C&CHQ) provided evidence of internal reliability. The CPCHILD and the CP-QOL-Child had evidence of test-retest reliability and DISABKIDS had evidence of inter-rater reliability. There were no published data on the responsiveness of these outcome measures.The CPCHILD and the CP QOL-Child demonstrated the strongest psychometric properties and clinical utility. Further work is needed, for all measures, on data for sensitivity to change. Cerebral Palsy (CP) defines a group of conditions, arising from an injury to the developing brain and occurs in 2.0 children per 1000 live births -5. The WQuality of life measures can either be generic , for example the KIDSCREEN , or be cIncreasingly, research and clinical practice is focusing on interventions not only to improve biomechanical alignment or functional outcomes for children with CP but also to positively improve QOL. Clinicians need to utilise outcome measures that accurately assess QOL in these children to provide evidence that their management strategies are influencing a child's QOL. The aim of this review therefore was to systematically identify all available condition specific QOL outcome measures for school aged children with CP, and to evaluate their psychometric properties and clinical utility.Articles were identified from a systematic search of the following computerized bibliographic databases: CINAHL (1982-October 2009), Medline (1950-October 2009), EMBASE (1988-October 2009), AMED (1985-October 2009), PsychINFO (1967-October 2009), PEDro (1929-October 2009), the Cochrane Library and ERIC (1966-October 2009). The keywords used were "quality of life," "cerebral palsy," "children" and "outcome measure," along with relevant MeSH terms and synonyms and searches were combined to obtain the final yield. Further articles were identified through citation tracking using the Web of Science databases, manual checking of the reference lists of included articles, and consultation with experts in the field.Outcome measures were included if they were designed to measure quality of life, according to the WHO definition, in children with CP aged 4 to 18 years and were written in English. This lower age limit was chosen so as to make certain a correct diagnosis of CP.Outcome measures were excluded if they were a generic QOL outcome measure or measured a construct other than QOL such as functional or health status and therefore did not meet the WHO definition. Functional status was described as a child's capacity to fulfill the requirements of day-to-day living, including societal contributions and personal up-keep , for exaTwo independent reviewers  excluded papers from the initial search yield on the basis of title and abstract. Full text articles were sourced where the title and abstract did not provide enough information about whether the inclusion criteria were met. Any disagreements over which papers to include or exclude were discussed with a third reviewer (RG) until a consensus was reached.Quality assessment was completed by the two independent reviewers , using a modification of the CanChild Outcome Measures Rating Form and Guidelines ,14, an aThe modified rating form consisted of eleven items which were applied to assess clinical utility ; and psychometric properties; including scale construction, standardization, reliability , validity  and responsiveness.Evidence for each aspect of quality measurement was scored as excellent (3 points), adequate (2 points), poor (1 point), or a no evidence available option was given (zero points). To be allocated 3 points there must have been at least two high quality published papers reporting strong evidence for the outcome measure in question. A score of 2 points required 1-2 well-designed studies with adequate to excellent results. If poor quality studies were conducted; or poor levels of evidence shown, a score of 1 was given. Such cut-offs were put into place so that only outcome measures which had a body of high-quality evidence of psychometric properties, along with high levels of clinical utility would be considered as excellent.Data were extracted by two reviewers  using a standardized form on the theoretic construct of the outcome measure, the respondent(s), standardization measures available , the target population, and the cost and training involved. Information on validity, reliability and responsiveness was also tabulated for each of the outcome measures by the two reviewers , based on the evidence sourced from publications. The quality of psychometric properties and clinical utility were then ranked by the two reviewers.The systematic search yielded 776 references of which 39 papers remained after review of the title and abstract. The full text of these papers were retrieved and assessed by two independent reviewers  and a further 31 papers were excluded . Importantly, the process for developing both the CP QOL-Child and the DISABKIDS included discussion and consultation with children who have CP. The basic premise for the C&CHQ was sourced from an earlier outcome measure, The Caregiver Questionnaire . InformaAll outcome measures were designed to be completed by parents (parent report), and three of the five measures also had a child report version, administered to children eight years and older; CP QOL-Child , DISABKIIn the eight studies reporting the measures only four papers reported on the GMFCS levels of participants -18,22. OQuality assessment found two outcome measures  that were considered to be of a high standard based on the aforementioned ratings. Two measures (DISABKIDS and PedsQL 3.0) were considered to be moderately constructed, while the C&CHQ was scored as a poor outcome measure on the quality scale used Table .The definition of QOL as described by Bjornson and McLaughlin  compromiThe available data on the psychometric properties of the five included measures are presented in Table Four of the five outcome measures  reported data on the internal reliability of the domains  Table . The CPCIdeally, therapists and researchers hoping to assess QOL in children with CP should have a choice of valid, reliable, easy to administer, low cost instruments, suited to the cultural and societal background of the children involved. This review reported and evaluated the psychometric properties and clinical utility of the condition specific outcome measures currently used to measure QOL in children with CP. Several areas were identified where further research is required including, data supporting concurrent validity, retest reliability and the responsiveness of the outcome measures. Based on the collected psychometric and clinical utility data of the included studies, the CPCHILD and the CP QOL-Child were the strongest outcome measures for evaluating QOL in school aged children with CP. The CP QOL-Child was the only outcome measure to have been developed with a firm theoretical underpinning of QOL.In the process of identifying and evaluating available outcome measures, the agreement of each to the accepted definition of QOL was assessed. Only one outcome measure fulfilled the two-part definitional criteria of QOL being measured across broad domains and being a measure of well-being (CP QOL-Child). It is recommended that clinicians and researchers utilise outcome measures that fulfil the requirements of the accepted definition. Self-evaluation of well-being has been theorised to stem from positive internal attitudes and feelings ; accordiAll five outcome measures available to measure QOL in school aged children with CP have limited evidence of validity. In three studies ,17,22 thWith the exception of the CPCHILD and the CP QOL-Child, outcome measures evaluated in this review did not provide evidence to support their concurrent validity. While there is no agreed 'gold standard' QOL measure to compare these CP condition specific outcome measures to, researchers could analyse the correlations between their outcome measure and a combination of other validated and reliable QOL measures. Accordingly, the CP QOL-Child was validated against the KIDSCREEN, a generic measure of QOL . Such reAs QOL is a personal perspective of an individual's well-being, testing reliability may be seen by some as problematic. In theory, it should be possible; with the absence of any major life changes, the results of consecutive applications of a QOL questionnaire should be consistent. There was no evidence for re-test reliability for three of the five QOL outcome measures; the C&CHQ, DISABKIDS and PedsQL 3.0. An assessment of re-test reliability for both the child and parent report was conducted for the CP QOL-Child, with applications of the questionnaire occurring at baseline and two weeks. Additional questions were administered after the two week period to gauge for any major life events during that time. Given this limited evidence for re-test reliability, it would be hard for clinicians and researchers using these outcome measures to determine if changes have really occurred following an intervention.This review identified that there is a lack of data on responsiveness, measurement error and minimally clinically significant difference scores for all of the measures. While the C&CHQ presented data on sensitivity to change, there was a potential bias in that the parents reporting the scores knew of the change in medical management. As rehabilitation studies are rarely masked to treatment allocation, it is problematic for parents to report perceived QOL without knowledge of treatment allocation, introducing bias. Information on sensitivity and responsiveness is important as increasingly QOL measures are being used in research studies. Until there is empirical evidence on the sensitivity to change and measurement error of these outcome measures, we cannot properly interpret results obtained from these outcome measures. The condition specific outcome measures for measuring QOL have only recently been developed, thus information regarding the appropriate minimally clinically significant change for each of the measures is now needed. It needs to be clear whether a change in domain or total score correlates to a clinically important change in QOL.Ceiling and floor effect sizes were reported for only one outcome measure (DISABKIDS chronic generic). This scale was designed as a 'chronic generic measure', including not only children with CP, but other paediatric conditions, thus, some questions may not be as appropriate as in other outcome measures. It is a positive indication of the validity of the given outcome measures if such effects did not generally occur. It would be expected that ceiling and floor effects would only occur if an outcome measure was inappropriately used on a population, for example a commonly erroneously used health status measure such as the PODCI, which is often referred to as a measure of QOL .During compilation of the studies in this review, the lack of reported demographic details of the population of interest in published works was evident. One short-coming was the lack of information regarding the cognitive abilities of children taking part in the self reporting of QOL. Children with CP may have cognitive impairments and such information is vital to researchers when deciding on whether an outcome measure to assess QOL is appropriate for a particular client or not. The CPCHILD specifically focused on children with greater physical impairment (children with GMFCS classifications III to V) and relied on parents' report of their child's QOL .Another point of interest was the wide age ranges that were used in four of the studies -17,22. WA limitation of this review was that potentially relevant articles were excluded if they were not written in the English language. Other limitations were the relatively recent development of the QOL outcome measures, resulting in a paucity of data on the ability of the measures to detect clinically important changes in QOL due to interventions.Taking into account the evidence for reliability and validity, the ease of access, the relatively quick completion time, and the free availability, the CP QOL-Child and the CPCHILD were found to be the strongest measures of QOL in children with CP. The CP QOL-Child was the only measure which wholly fulfilled the definitional criteria of QOL. As yet however, there is no data published on sensitivity and limited data on the child report questionnaire for the CP QOL-Child. More broadly, the term "Quality of Life" is used with much inconsistency. Both research and clinical practice would benefit from the uniform understanding and use of an agreed, consensus driven definition.Contributing author RB was involved in the consultation processes which lead to the development and psychometric testing of the CP QOL-Child questionnaire. This bias was eliminated by RB not being involved with the quality analysis of the questionnaires.SC assisted in developing the search strategy and modifying the quality analysis tool, conducted the search, screened publications for inclusion, applied inclusion and exclusion criteria, performed data extraction and quality analysis and drafted the manuscript. NS contributed to developing the study methodology, assisted in developing the search strategy and modifying the quality analysis tool, oversaw the assessment of each measure and provided input at each stage of the drafting of the review. KY screened publications for inclusion and applied the inclusion and exclusion criteria. RG assisted with application of inclusion and exclusion criteria, performed data extraction and quality analysis. LS provided methodological input, background information and clinically applicable support. RB provided background information, assisted in developing the review methodology, assisted in developing the search strategy and modifying the quality analysis tool and provided input at each stage of the drafting of the review. All authors have been involved in the revision of this document and have approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/10/81/prepub


Abdominal migraine is a commonly described migraine variant in children and young adults, but associations with Alice in Wonderland syndrome and lilliputian hallucinations are exceptional.A 20 years-old male experienced frequent and prolonged attacks of abdominal colic associated with autonomic manifestations started at the age of ten. At the age of 17, he additionally described prolonged attacks (≥ 7 days) of distortions of shape, size or position of objects or subjects. He said "Quite suddenly, objects appear small and distant (teliopsia) or large and close (peliopsia). I feel as I am getting shorter and smaller "shrinking" and also the size of persons are not longer than my index finger (a lilliputian proportion). Sometimes I see the blind in the window or the television getting up and down, or my leg or arm is swinging. I may hear the voices of people quite loud and close or faint and far. Occasionally, I experience attacks of migrainous headache associated with eye redness, flashes of lights and a feeling of giddiness. I am always conscious to the intangible changes in myself and my environment". There is a strong family history of common migraine. Clinical examination, brain-MRI and EEG were normal. Transcranial magnetic stimulation and evoked potentials revealed enhanced cortical excitability in multiple brain regions. Treatment with valproate resulted in marked improvement of all clinical and neurophysiological abnormalities.The association between the two migraine variants  might have clinical, pathophysiological and management implications. I think this is the first description in the literature. Migraine variants (MVs) or migraine equivalents exhibit themselves in forms other than head pain. MVs are less recognized and poorly understood entities of migraine. They are encountered in 3-5% of patients with migraine and usually affect children and young adults . AbdominMVs should be differentiated from organic, psychiatric or central nervous system diseases with similar clinical presentation. In MVs, various molecular and cellular mechanisms may increase the susceptibility of cortical spreading depression (CSD), a main pathophysiologic mechanism associated with migraine. CSD is a slow cortical depolarization that progress from one brain area to its contiguous resulting in transient oligemia or ischemia, followed by hyperemia in different cortical areas and the associated multiple neurological phenomena .Twenty years-old Egyptian male was referred by an internist for neurological assessment. At presentation, the patient was curled up in a fetal position and only bent his head in response to questions, because he was experiencing intense and prolonged attacks of colic centered in his mid-abdomen. The colic attacks started at the age of ten. Early at the onset, the attacks were shorter in duration (few hours to 24 hours) and recurred every 3-5 months. They progressed in duration and frequency as in the last year before presentation, they were recurring weekly and each continued up to 72 hours. The attacks were accompanied by nausea, abdominal flushing, pallor, tachycardia and diarrhea (but never vomiting). The patient said that abdominal discomfort leaves as suddenly as it comes, offering no clue to when it will return. But he recognized eating fish or its products as strong triggers for the colic. The pain was severe enough to make him refuse to eat or drink for prolonged periods. This resulted in unintentional weight loss (the patient was 45 kilos at presentation), slowed growth and limited life activities and school attendance. The referral internist excluded the presence of organic disorder as a cause of patient's manifestations based on medical evaluation and unremarkable laboratory tests , abdominal imaging and endoscopic examinations. Long-term anti-epileptic treatment with carbamazepine was prescribed to the patient by a pediatrician based on the presence of epileptic activity in the electroencephalogram (EEG). Long-term treatment with colchicine was prescribed by another internist because of the misdiagnosis as Mediterranean Fever although the patient never experienced attacks of fever or serositis.At the clinic and in front of the consulting neurologist, the patient developed the attacks of abdominal colic. The patient was not only feeling miserable, but looked it too. He was pale and curled up with sucked abdomen. Neither loss of consciousness nor postictal confusion was witnessed. Immediate EEG was normal.At the age of 17, the patient developed abnormal visual phenomena in between the attacks of abdominal colic which lasted longer than a week. The patient said: "Quite suddenly everything seems strange, unusually I see objects small and distant (teliopsia) or large and close (peliopsia). I feel that I am getting shorter and smaller "shrinking" and also the size of persons are not longer than my index finger (a Lilliputian proportion). I see the same by either eye separately. I see the blind in the window or the television gets up and down, or my leg or arm is swinging. I hear people's voices loud and close or faint and far. I am always conscious of the intangible changes in myself and my environment. I am least likely to be distressed by those hallucinations as I find them non-threatening and I also get familiar with them. Occasionally at the end of the third day of an abdominal attack, I develop attacks of throbbing hemicranial headache associated with eye redness, flashes of lights and a feeling of giddiness which lasts no longer than 15 minutes". There is a strong family history  of recurrent hemicranial headaches associated with eye redness, anxiety, nausea and vomiting, that lasted for a period of hours to 3 days and sometimes improved with NSAIDs. The manifestations are suggestive of a common migraine disorder. There were no previous histories of trauma, drug ingestion, epilepsy, other central nervous system or psychiatric disorders.Diagnostic testing was done to distinguish primary from secondary causes that share similar features. Diagnostic workup did not reveal another cause. MRI-brain (regular and diffusion-weighted) was normal. Interictal video EEG using basal temporal  and sphenoidal electrodes did not reveal epileptiform abnormalities. For research purpose, sensory evoked potentials  and transcranial magnetic stimulation (TMS) were done five times  to assess the excitability and function of the motor and sensory cortices. In each test of SEPs, a peripheral sense organ is electrically stimulated and conduction velocities were recorded for central sensory pathways .EPs recordings revealed enhanced amplitude of P100 of VEP and delayed N20  of SSEP. TMS recordings revealed increased size of MEPs and short CSP  was prescribed as a prophylactic treatment. VPA is a known antiepileptic drug which increases brain levels of GABA or enhances GABA action. Occasionally, eletriptan (Relpax 40 mg per needed) was prescribed as a treatment for acute migraine. Triptans constrict blood vessels and possibly inhibit inflammation of the blood vessels . Shortly after the start of treatment, the patient experienced marked clinical and neurophysiological improvement tables . The decInterestingly, as the patient recognized eating fish or its products as a trigger for abdominal colic, he frequently tried fish to evaluate the therapeutic efficacy of VPA.This study was conducted according to the principles established in Helsinki and approved by Assiut University Hospital ethics committee. Informed written consent was obtained from the patient to publish the details of his clinical history, laboratory and imaging data.In clinical practice, the presence of family history of common migraine and a trigger for the attack remain the key tools to explain why this patient was born with a liability for migraine. In general, heritability in migraine is estimated to be 40-60% . MigrainAnalyzing the clinical and neurobiological characteristics, the onset of autonomic phenomena, which was manifested as abdominal colic, abdominal flushing, nausea, pallor, diarrhea, tachycardia and fear or anxiety, simulate to a great extent auras of temporal lobe epilepsy (TLE). The amygdale, hypothalamus and medullary cranial nerve nuclei are possible generators of abdominal colic and autonomic manifestations, in support: 1) discharges arising in the amagdala and transmitted to the gut via dense direct projections to the dorsal motor nucleus of the vagus might be responsible for gastrointestinal tract (GIT) symptoms in TLE, 2) sympathetic pathways from the amygdala to the GIT can be activated via the hypothalamus, 3) there are direct sensory pathways from the bowel via the vagus nerve to the solitary nucleus of the medulla which are heavily connected to the amygdala. These pathways can be activated during intestinal contractions, and 4) recently, it has been suggested that orexinegic neurons in the lateral hypothalamus may be a generator for a migraine attack .Additionally, at adolescence, the patient developed manifestations of Alice in Wonderland Syndrome which mainly composed of complex visual illusions. The described distortions of objects and body images in absence of a concomitant attack of vertigo are suggestive of involvement of the posterior part of the right parietal lobe (non-dominant) with and without involvement of the temporal lobe. The occurrence of auditory illusions (consisted of loudening or muffling of ambient sounds) suggests involvement of the posterior superior temporal lobule. While the primary visual hallucinations associated with migraine suggest involvement of the striate and extra-striate regions of the occipital lobe . PatientThe presence of atypical manifestations, progressive weight loss and reduced growth mandate medical diagnostic workup for exclusion of an organic cause. Neuroimaging and neurophysiologic assessments were needed to exclude other causes of AWLS as epilepsy , infectiSEPs and TMS results indicate cortical hyperexcitability in multiple brain regions or diffuse brain involvement. Enhanced amplitude of P100 of VEP is indicative of occipital cortical hyperexcitability. Delayed N20  of SSEP is indicative of parietal lobe dysfunction. Increase in the size of motor responses or MEPs and short CSP are indicative of motor neuronal hyperexcitability. In accordance, independent evidences from VEPs and TMS, recordings and psychophysics indicate the presence of deficient habituation and changes in neuronal excitability during and in between the attacks of migraine ,32.nd, 3rd and 5th cortical layers. Fast and early cortical motor inhibitions are mediated by GABAA receptors, while slow and late G-protein-coupled inhibitions are mediated by GABAB receptors. In fact, neuronal excitability is governed by the complex interplay of channel currents. Changes in ion channels as a result of hereditary mutations could result in minimal or episodic changes in neuronal micro-environment. These changes might be sufficient to cause transient neuronal hyperexcitability. It has been found that the subpopulations of cortical neurons have different physiological properties in response to different stimuli, thus might be differentially modulated in migraine extremes. Furthermore, expression of a single mutation in different cell types, networks and developmental periods has been suggested to underlie the coexistence of common migraine, atypical migraine auras, or a non-epileptic paroxysmal disorder in one individual or family [The neurophysiologic changes observed in migraine could offer explanation for the migraine mechanism. In general, cortical hyperexcitability is due to imbalance between the cortical inhibitory GABA-ergic (gamma aminobutyric acid) and excitatory glutaminergic circuits . VPA incr family . These eWe suggest that the occurrence of two different migraine phenomena in one patient might be the result of chronicity and the concomitant central sensitization process . Due to The authors declare that they have no competing interests.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/10/2/prepub


The authors present an objective review of what is new in endourology instrumentation, based on up-to-date scientific data gathered from meetings, state-of-art lectures and current literature. The main scope of this review is to highlight the most recommended device options for each step of an ureteroscopy, in order to offer best care to patients. Ureterorenoscopy has firmed its importance in the urology surgery arsenal. The technological advances in this field, specifically the innovations in ureteroscope design, surgical technique, and accessory instrumentation, have allowed not only for broadening of diagnostic potential of ureteral and intrarenal infirmities but also it has provided the means for treating them once diagnosed.Associated with this technological evolution is an ever-widening array of instruments available to endourologists who need to be up-to-date on the advances of the endourological devices brought in to market, in order to offer the best care to patients.This article is an objective review of what is new in endourology instrumentation, based on state-of-art lectures, expert meetings, and current literature.The placement of a safety wire facilitates and maintains access to the upper urinary tract. Soft-tip nitinol Glidewire  is the safest wire for the initial access to the ureter since it is less likely to perforate and more likely to bend when a point of obstruction is encountered. In contrThe use of a ureteral access sheath has been demonstrated to help facilitate ureteral re-entry, decrease operative time and cost, minimize patient morbidity, and optimize overall success with intrarenal ureteroscopic surgery.Recent clinical and in vitro trials have demonstrated that the Cook Flexor sheath  was rated superior to the Applied Access Forte XE  with regard to the ease of placement, instrument passage, and stone extraction. The Cook3A new balloon-based ureteral access sheath combines radial balloon dilation and access sheath placement in a single step that reduces both the axial force and urothelial disruption, improving saline flow, causing less trauma to the urothelium, and showing an easy insertion in a porcine model.The newer, actively deflecting flexible ureteroscopes offer increased lower pole access compared to the older passively deflecting scopes by one of two mechanisms: either separate dual-lever primary and secondary deflection that offers increased unidirectional downward deflections of 270 degrees  or increased bidirectional primary deflection that offers 270 degree deflection in both directions .A comparison of commercially available flexible ureteroscopes concluded that the larger working channel of the Wolf ureteroscopes provides superior irrigant flow as well as better optics through the unique fused quartz bundle compared to glass fiberoptic bundles. The WolfAnother critical consideration is the durability of the flexible ureteroscope. The first flexible scope durability study showed that Gyrus-ACMI DUR-8-Elite was the most durable flexible ureteroscopeModern digital flexible ureteroscopes  improved maneuverability and visibility compared to the conventional fiberoptic scopes as they have eliminated the light cord and improved optical resolution with CMOS technology . This new generation of scopes also employs the latest in light technology the LED (light emitting diode), a durable and cheap cool light, eradicating the traditional Xenon light, a very expensive, hot, and less-durable light source. In addition, the absence of optic fibers in the shaft of the flexible scope provides better deflection and simplicity to the instrument, which lowers costs and results in more durability.While a number of different endoscopic lithotrites, such as ultrasonic, electrohydraulic, pneumatic, and laser have been utilized in the past, holmium laser has come to dominate intracorporeal lithotripsy. Holmium:YAG laser lithotripsy causes chemical decomposition of calculi predominately as a consequence of a photothermal mechanism to create a vaporization bubble that subsequently destabilizes the stone.The laser fibers are thin and flexible, making them ideal for passing through the working channel of a flexible ureteroscope. In contrast to other lasers, holmium laser lithotripsy has been shown to fragment all compositions of urinary calculi, as well as produce smaller stone fragments than pneumatic or electrohydraulic lithotripsy. In addition, the holmium laser energy is efficiently absorbed in a fluid medium, minimizing the risk of urothelial injury compared to the electrohydraulic lithotrite. Furthermore, retropulsion of the stone is less likely than with a pneumatic lithotrite.In a comparison study, the stone-free rates both at the end of the ureteroscopy and 3-month post-procedure were significantly higher for holmium versus electrohydraulic lithotripsy.Performance and safety studies of commercially available holmium laser fibers demonstrated that the Dornier Lightguide 200 was the most likely of small fibers (200-273 mm) to fracture and damage a flexible ureteroscope, while the Lumenis 272 (Coherent) and the Innova Quartz 400 (Gyrus-ACMI) were the most durable in their size class.A variety of stone retrieval devices are utilized in ureteroscopy under different circumstances. Important properties of these devices include visibility during stone manipulation, sufficient radial force to open in the ureter, and the ability to capture, retain, or, if necessary, disengage a stone. Alligator or rat tooth forceps are favored by some due to the reversible grasp, reusability, and corresponding cost-effectiveness. However, the large size (3F or greater) and weak grasp impact their effectiveness.Nitinol-basket based designs, however, are more versatile and atraumatic in stone retrieval due to the unique pliability of the wires and the flexibility to allow full lower pole deflection of a flexible ureteroscope in the majority of cases.16 In genin situ, preventing retrograde ureteral stone migration.[The 1.5F Sacred Heart Halo  has been demonstrated in a calcyeal model to be the most efficient at stone retrieval of smaller fragments. In additigration. These twThe Cook NGage is a relatively new device that has coupled the properties of a three-prong grasper with the entrapment capability of a regular tipples nitinol basket. NGage provides easy grasp-and-release of the stone, making it possible to relocate the calculus from the lower pole to the upper pole or to a straight forward path to expedite and optimize laser lithotripsy.A variety of devices are utilized to prevent stone migration during intracorporeal lithotripsy in the ureter. The Stone Cone (Boston Scientific) consists of concentric coils which, when placed proximal to calculi, act to prevent proximal retropulsion of stone fragments during lithotripsy. The deviUreteral stents are used for both the prevention and treatment of ureteral obstruction following ureteroscopy. A ureteral stent is always left after placement of a ureteral access sheath, as anecdotal experience with not stenting in this situation is a higher prevalence of significant transient pain for 24 hours. The Bard Inlay 6F ureteral stent  has been associated with less severe urinary symptoms than other ureteral stents.Interestingly, in a recent multicenter clinical trial the use of a drug-eluting stent  to decrease stent-related discomfort with promising results has been demonstrated, especially in a selected group of patients such as young adults.New endourology devices are always being idealized and some have already been tested in “in vivo” animal studies. The first noteworthy innovation was presented at the American Urological Association Meeting in Chicago and it was about the use of iron-oxide microparticles that bind to the calcium component of the stones turning them attractable to a new magnet-tip basket, expediting and optimizing stone extraction during endoscopic surgery.Another interesting study was presented at the European Association of Urology at Stockholm evaluating the use of isoproteronol  as an intrarenal lowering pressure agent during ureteroscopy. The concept of using a pharmacological agent in the irrigating solution during ureteroscopy is of fascinating potential.These are a few of interesting ideas that can potentially result in better outcomes for the patients and facilitate the procedure for the endourologists.The growing prevalence of flexible ureteropyeloscopy as a diagnostic and therapeutic tool for endourologists is due in large part to the dramatic evolution in instrument design and technology. Having the right instrument in the right situation will help facilitate consistent and positive operative outcomes.