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Reviewer Acknowledgement 2012

Tim Shipley — 2013-05-22T00:00:00Z

Contributing reviewersThe editors of BMC Musculoskeletal Disorders would like to thank all our reviewers who have contributed to the journal in Volume 12 (2012).

The use and costs of health and social services in patients with longstanding substance abuse

Corinna Vossius — 2013-05-22T00:00:00Z

Background: Persons with longstanding substance abuse might become increasingly dependent on help by the public, eventually requiring permanent care. In 2006 the municipality of Stavanger established a so-called addiction ward for these clients, comprising 17 beds at the largest municipal nursing home. We assumed that the residents of this ward were high consumers of health care and social services during the last months preceding their admission. The aim of the study was to register the type and extent of services that were claimed by this client group during the last six months prior to admission, and to calculate the costs that were caused. Further, we estimated the incremental costs for nursing home placement. Methods: In 15 residents from the addiction ward the use of all welfare services during the six months prior to admission were registered. Costs were calculated by unit costs from a municipal, national and societal perspective. Results: Mean total costs during this period were [euro sign]32 474. Approximately half of these costs were borne by state-funded institutions, and half were borne by the municipality. The clients used a great variety of services aimed at subsistence, health care and support in independent living, while services aimed at drug withdrawal were not claimed. There was no correlation between costs and the level of functioning. The incremental costs for nursing home admission were borne by the municipalities. Conclusion: Persons with longstanding substance abuse represent a group with a high use of welfare resources and hence cause high costs. However, our findings do not indicate any correlation between the amount of services rendered and the level of functioning. Further research should focus on the identification of the clients' need for support in order to facilitate targeted interventions that might prevent further deterioration and, finally, the need for permanent care.

Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2

Mathieu Milh — 2013-05-22T00:00:00Z

Background: Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found mutated in about 10% of EOEE patients. Our objective was to confirm that KCNQ2 was an important gene to include in the diagnosis workup of EOEEs and to fully describe the clinical and EEG features of mutated patients. Methods: We have screened KCNQ2 in a cohort of 71 patients with an EOEE, without any brain structural abnormality. To be included in the cohort, patient's epilepsy should begin before three months of age and be associated with abnormal interictal EEG and neurological impairment. Brain MRI should not show any structural abnormality that could account for the epilepsy. Results: Out of those 71 patients, 16 had a de novo mutation in KCNQ2 (23%). Interestingly, in the majority of the cases, the initial epileptic features of these patients were comparable to those previously described in the case of benign familial neonatal epilepsy (BFNE) also caused by KCNQ2 mutations. However, in contrast to BFNE, the interictal background EEG was altered and displayed multifocal spikes or a suppression-burst pattern. The ongoing epilepsy and development were highly variable but overall severe: 15/16 had obvious cognitive impairment, half of the patients became seizure-free, 5/16 could walk before the age of 3 and only 2/16 patient acquired the ability to speak. Conclusion: This study confirms that KCNQ2 is frequently mutated in neonatal onset epileptic encephalopathy. We show here that despite a relatively stereotyped beginning of the condition, the evolution is highly variable in terms of epilepsy and of cognitive evolution.

Incidence and costs of bleeding-related complications in French hospitals following surgery for various diagnoses

Xin Ye — 2013-05-22T00:00:00Z

Background: Limited information is available on the epidemiology and economics of bleeding during surgery in France.MethodThe objective of this study was to examine the incidence, costs and length of stay (LOS) of bleeding-related complications during various surgical procedures.A retrospective DRG (diagnosis-related group) analysis was conducted using the French National database PMSI (Programme Medicalise des Systemes d'Informations). Patients undergoing surgery during 2008 were identified according to their DRG classifications and those with at least one episode of secondary haemostasis and blood transfusion (according to French procedure codes) were designated as 'with bleeding' (WB). The analysis focussed on DRGs where >=10% of patients presenting with bleeding and compared them to patients who did not require blood transfusions (i.e. without bleeding: WoB).Hospital LOS and costs (age and gender adjusted) were compared between WB and WoB patients within each DRG. Hospitalisation periods exceeding the LOS average (derived from the PMSI database) were compared using multivariate logistic regression adjusted for patient characteristics. Results: Amongst all 88 different surgical DRGs recognised by the French database 24 (totalling 321,657 hospitalisations) yielded WB rates >=10% (range 10.3-25.3%). The highest DRG rates were for transplantations, cardiac and major orthopaedic surgery, vascular and solid organ surgery.The average LOS for the WB population (adjusted for age, gender, number of procedures and secondary diagnoses) were 3.38 days (26.5%) longer than for the WoB population (p < 0.001). The average adjusted LOS costs for a WB patient were estimated at [euro sign]12,087, and for a WoB patient [euro sign]10,086 i.e. 19.9% higher than for WB patients (p < 0.001). The overall mean LOS was exceeded by 42.3% of WB patients compared to 37.0% of WoB patients (p < 0.001). Also, WB patients were more likely to exceed the average LOS than were WoB patients (Odds Ratio (OR) = 1.09, p < 0.001), after adjusting for patient characteristics. Conclusions: The present study for France demonstrates a significant increase of hospital LOS and associated costs following post-surgical bleeding, supporting the need for blood conservation strategies.

Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model

Tao Hu — 2013-05-22T00:00:00Z

Background: Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown. Methods: HEM (human epidermal melanocyte) cells and human melanoma cells with the wild-type G6PD gene (A375-WT), G6PD deficiency (A375-G6PD[increment]), G6PD cDNA overexpression (A375-G6PD[increment]-G6PD-WT), and mutant G6PD cDNA (A375-G6PD[increment]-G6PD-G487A) were subcutaneously injected into 5 groups of nude mice. Expressions of G6PD, STAT3, STAT5, cell cycle-related proteins, and apoptotic proteins as well as mechanistic exploration of STAT3/STAT5 were determined by quantitative real-time PCR (qRT-PCR), immunohistochemistry and western blot. Results: Delayed formation and slowed growth were apparent in A375-G6PD[increment] cells, compared to A375-WT cells. Significantly decreased G6PD expression and activity were observed in tumor tissues induced by A375-G6PD[increment], along with down-regulated cell cycle proteins cyclin D1, cyclin E, p53, and S100A4. Apoptosis-inhibited factors Bcl-2 and Bcl-xl were up-regulated; however, apoptosis factor Fas was down-regulated, compared to A375-WT cells. Moderate protein expressions were observed in A375-G6PD[increment]-G6PD-WT and A375-G6PD[increment]-G6PD-G487A cells. Conclusions: G6PD may regulate apoptosis and expression of cell cycle-related proteins through phosphorylation of transcription factors STAT3 and STAT5, thus mediating formation and growth of human melanoma cells. Further study will, however, be required to determine potential clinical applications.

Boginia virus, a newfound hantavirus harbored by the Eurasian water shrew (Neomys fodiens) in Poland

Se Hun Gu — 2013-05-22T00:00:00Z

Background: Guided by decades-old reports of hantaviral antigens in the Eurasian common shrew (Sorex araneus) and the Eurasian water shrew (Neomys fodiens) in European Russia, we employed RT-PCR to analyze lung tissues of soricine shrews, captured in Boginia, Huta D[latin small letter l with stroke]utowska and Kurowice in central Poland during September 2010, 2011 and 2012.FindingsIn addition to Seewis virus (SWSV), which had been previously found in Eurasian common shrews elsewhere in Europe, a genetically distinct hantavirus, designated Boginia virus (BOGV), was detected in Eurasian water shrews captured in each of the three villages. Phylogenetic analysis, using maximum likelihood and Bayesian methods, showed that BOGV formed a separate lineage distantly related to SWSV. Conclusions: Although the pathogenic potential of BOGV and other recently identified shrew-borne hantaviruses is still unknown, clinicians should be vigilant for unusual febrile diseases and clinical syndromes occurring among individuals reporting exposures to shrews.

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease -- a combined tissue microarray, in vitro and in vivo study

Ágnes Márk — 2013-05-22T00:00:00Z

Background: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. Methods: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. Results: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents. Conclusions: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response.

Neuromimetic model of saccades for localizing deficits in an atypical eye-movement pathology

Pierre M Daye — 2013-05-22T00:00:00Z

Background: When patients with ocular motor deficits come to the clinic, in numerous situations it is hard to relate their behavior to one or several deficient neural structures. We sought to demonstrate that neuromimetic models of the ocular motor brainstem could be used to test assumptions of the neural deficits linked to a patient's behavior. Methods: Eye movements of a patient with unexplained neurological pathology were recorded. We analyzed the patient's behavior in terms of a neuromimetic saccadic model of the ocular motor brainstem to formulate a pathophysiological hypothesis. Results: Our patient exhibited unusual ocular motor disorders including increased saccadic peak velocities (up to ~1000 deg/s), dynamic saccadic overshoot, left-right asymmetrical post-saccadic drift and saccadic oscillations. We show that our model accurately reproduced the observed disorders allowing us to hypothesize that those disorders originated from a deficit in the cerebellum. Conclusion: Our study suggests that neuromimetic models could be a good complement to traditional clinical tools. Our behavioral analyses combined with the model simulations localized four different features of abnormal eye movements to cerebellar dysfunction. Importantly, this assumption is consistent with clinical symptoms.

Host response to cuckoo song is predicted by the future risk of brood parasitism

Sonia Kleindorfer — 2013-05-22T00:00:00Z

IntroductionRisk assessment occurs over different temporal and spatial scales and is selected for when individuals show an adaptive response to a threat. Here, we test if birds respond to the threat of brood parasitism using the acoustical cues of brood parasites in the absence of visual stimuli. We broadcast the playback of song of three brood parasites (Chalcites cuckoo species) and a sympatric non-parasite (striated thornbill, Acanthiza lineata) in the territories of superb fairy-wrens (Malurus cyaneus) during the peak breeding period and opportunistic breeding period. The three cuckoo species differ in brood parasite prevalence and the probability of detection by the host, which we used to rank the risk of parasitism (high risk, moderate risk, low risk). Results: Host birds showed the strongest response to the threat of cuckoo parasitism in accordance with the risk of parasitism. Resident wrens had many alarm calls and close and rapid approach to the playback speaker that was broadcasting song of the high risk brood parasite (Horsfield's bronze-cuckoo, C. basalis) across the year (peak and opportunistic breeding period), some response to the moderate risk brood parasite (shining bronze-cuckoo, C. lucidus) during the peak breeding period, and the weakest response to the low risk brood parasite (little bronze-cuckoo, C. minutillus). Playback of the familiar control stimulus in wren territories evoked the least response. Conclusion: Host response to the threat of cuckoo parasitism was assessed using vocal cues of the cuckoo and was predicted by the risk of future parasitism.

Medical services of a mulicultural summer camp event: experiences from the 22nd World Scout Jamboree, Sweden 2011

Ib Jammer — 2013-05-22T00:00:00Z

Background: Prevention and treatment of medical issues are the main task of a health service at a youth camp. However, only few reports about organisation and implementation of camp health care are available. This makes it difficult for future camp directors to plan and estimate the health care needed for a certain camp size. We summarize the experience in planning and running health care for the 22nd World Scout Jamboree (WSJ) 2011 in Sweden. Methods: During the WSJ, 40,061 participants from 146 nations were gathered in southern Sweden to a 12 day summer camp. Another 31,645 people were visitors. Members for the medical service were 153 volunteering medical professionals with different language and cultural backgrounds from 18 different countries. Results: Of 40,061 participants 2,893 (7.3%) needed medical assistance. We found an equal distribution of cases to approximately one third surgical, one third medical and one third unspecified cases. Much energy was spent on health prevention, hygiene measures and organizing of psychological support. Conclusions: A youth camp with a multicultural population and a size of a small city demands flexible staff with high communication skills. Special attention should be paid in prevention of contagious diseases and taking care of psychological issues.