bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of mood stabilisers in the treatment of impulsive or
repetitive aggression: systematic review and meta-analysis
Authors: Jones Roland M. , Arlidge James , Gillham Rebecca , Reagu Shuja , van den Bree Marianne , Taylor Pamela J. 
Published: February 2011

BackgroundIndividuals with repetitive or impulsive aggression in the absence of
other disorders may be diagnosed with intermittent explosive disorder
according to DSM–IV, but no such diagnostic category exists in ICD–10.
Mood stabilisers are often used off-license for the treatment of
aggression associated with a variety of psychiatric conditions, but their
efficacy in these and in idiopathic aggression is not known.AimsTo summarise and evaluate the evidence for the efficacy of mood
stabilisers (anticonvulsants/lithium) in the treatment of impulsive or
repetitive aggression in adults.MethodA meta-analysis of randomised controlled trials that compared a mood
stabiliser with placebo in adults without intellectual disability,
organic brain disorder or psychotic illness, identified as exhibiting
repetitive or impulsive aggression.ResultsTen eligible trials (489 participants) were identified A pooled analysis
showed an overall significant reduction in the frequency/severity of
aggressive behaviour (standardised mean difference (SMD) =–1.02, 95% CI
−1.54 to −0.50), although heterogeneity was high (I2 = 84.7%). When analysed by drug type, significant effects
were found in the pooled analysis of three phenytoin trials (SMD =–1.34,
95% CI −2.16 to −0.52), one lithium trial (SMD =–0.81, 95% CI −1.35 to
−0.28), and two oxcarbazepine/carbamazepine trials (SMD =–1.20, 95% CI
−1.83 to −0.56). However, when the results of only those studies that had
a low risk of bias were pooled (347 participants), there was no
significant reduction in aggression (SMD =–0.28, 95% CI −0.73 to 0.17,
I2 = 71.4%).ConclusionsThere is evidence that mood stabilisers as a group are significantly
better than placebo in reducing aggressive behaviour, but not all mood
stabilisers appear to share this effect. There is evidence of efficacy
for carbamazepine/oxcarbazepine, phenytoin and lithium. Many studies,
however, were at risk of bias and so further randomised controlled trials
are recommended.
Assisted suicide: why psychiatrists should engage in the
debate
Authors: Hotopf Matthew , Lee William , Price Annabel 
Published: February 2011

SummaryThere is an increasing appetite for a change in the law to allow assisted
suicide. This editorial suggests that psychiatrists should engage in the
debate because the issues at stake will affect us, and we are likely to have
a significant part to play were the law to be changed. We suggest that there
are three main areas where psychiatrists' expertise may be informative: (a)
the extent to which safeguards to limit the availability of assisted dying
to target groups can be applied safely and fairly, including to individuals
with psychiatric disorders; (b) the complexities inherent in assessing
mental capacity; and (c) the degree to which individuals adapt or change
their desires, particularly in relation to suicidal behaviours.
Questioning the ‘neuroprotective’ hypothesis: does drug treatment prevent brain damage in early psychosis or schizophrenia?
Authors: Moncrieff Joanna 
Published: February 2011

SummaryThe idea that psychotic disorders are characterised by progressive neurodegeneration that can be reversed by drug treatment is used to justify early treatment of increasing numbers of mostly young people. I argue that there is little evidence to support the view that old- or new-generation antipsychotics are ‘neuroprotective’, and some evidence that the drugs themselves may be responsible for the decline in brain matter observed in some studies.
Contribution of psychiatric disorders to occupation of NHS beds: analysis of Hospital Episode Statistics
Authors: Pillay Parvathy , Moncrieff Joanna 
Published: February 2011

Aims and methodWe looked at the contribution of psychiatric disorders to occupancy of National Health Service (NHS) beds in England in the past 11 years, using publicly available data on Hospital Episode Statistics from the financial years 1998–1999 to 2008–2009.ResultsPatients with psychiatric disorders occupied between 14 and 16% of NHS beds in each year examined, and schizophrenia and mood disorders were among the top ten medical diagnoses of people occupying beds in every year. In terms of duration of admission, many individuals with psychiatric disorders, including schizophrenia and mood disorders, had a longer length of admission than those with other medical conditions. In 2008–2009 mean duration of admission for people with schizophrenia was 108 days and for people with mood disorders 42 days. In comparison, people with cerebrovascular disease stayed in hospital for 20 days on average.Clinical implicationsDespite modern treatments, people with psychiatric disorders occupy a large proportion of NHS beds and stay in hospital for considerably longer than those with other medical conditions. Since the independent sector is providing increasing amounts of long-term in-patient care, these figures are likely to underestimate the total burden and costs of treating psychiatric disorders. Community services designed to reduce admissions have yet to have any substantial impact on bed use.
Randomized Trial of Carboplatin Versus Radiotherapy for Stage I Seminoma: Mature Results on Relapse and Contralateral Testis Cancer Rates in MRC TE19/EORTC 30982 Study (ISRCTN27163214)
Authors: Oliver R. Timothy D. , Mead Graham M. , Rustin Gordon J.S. , Joffe Johnathan K. , Aass Nina , Coleman Robert , Gabe Rhian , Pollock Philip , Stenning Sally P. 
Published: February 2011

Purpose Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported. Patients and Methods Random assignment was between RT and one infusion of carboplatin dosed at 7 × (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202). The trial was powered to exclude a doubling in RFRs assuming a 96-97% 2-year RFR after radiotherapy (hazard ratio [HR], approximately 2.0). Results Overall, 1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n = 904). RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89). One death as a result of seminoma (in RT arm) occurred. Patients receiving at least 99% of the 7 × AUC dose had a 5-year RFR of 96.1% (95% CI, 93.4% to 97.7%) compared with 92.6% (95% CI, 88.0% to 95.5%) in those who received lower doses (HR, 0.51; 95% CI, 0.24 to 1.07; P = .08). There was a clear reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT, n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03), and elevated pretreatment follicle-stimulating hormone (FSH) levels (> 12 IU/L) was a strong predictor (HR, 8.57; 95% CI, 1.82 to 40.38). Conclusion These updated results confirm the noninferiority of single dose carboplatin (at 7 × AUC dose) versus RT in terms of RFR and establish a statistically significant reduction in the medium term of risk of second GCT produced by this treatment.
Differences in Sleep Disturbance Parameters Between Oncology Outpatients and Their Family Caregivers
Authors: Carney Sara , Koetters Theresa , Cho Maria , West Claudia , Paul Steven M. , Dunn Laura , Aouizerat Bradley E. , Dodd Marylin , Cooper Bruce , Lee Kathryn , Wara William , Swift Patrick , Miaskowski Christine 
Published: February 2011

Purpose This study compared the occurrence rates for and severity ratings of sleep disturbance in patient-family caregiver (FC) dyads. Patients and Methods In total, 102 dyads were recruited from two radiation therapy (RT) departments. Patients and their FCs completed the Pittsburgh Sleep Quality Index (PSQI) and the General Sleep Disturbance Scale (GSDS) and wore wrist actigraphs to obtain subjective and objective measures of the occurrence and severity of sleep disturbance at the initiation of RT. Match paired t tests were used to evaluate for dyadic differences. Results No differences were found in the occurrence of clinically significant levels of sleep disturbance between patients and their FCs that ranged between 40% and 50% using subjective and objective measures. Few differences were found in the severity of any of the sleep-wake parameters between patients and FCs using both the subjective and objective measures of sleep disturbance. Conclusion The findings from this study suggest that patients with cancer and their FCs experience similar levels of sleep disturbance and that both groups could benefit from interventions that aim to promote restful sleep. In addition to routine and systematic assessment of sleep disturbance by oncology clinicians, interventions are needed that take into account the specific needs of the patient and the FC as well as the potential for partners' sleep patterns to influence one another.
Impact of Pretransplantation Minimal Residual Disease, As Detected by Multiparametric Flow Cytometry, on Outcome of Myeloablative Hematopoietic Cell Transplantation for Acute Myeloid Leukemia
Authors: Walter Roland B. , Gooley Ted A. , Wood Brent L. , Milano Filippo , Fang Min , Sorror Mohamed L. , Estey Elihu H. , Salter Alexander I. , Lansverk Emily , Chien Jason W. , Gopal Ajay K. , Appelbaum Frederick R. , Pagel John M. 
Published: February 2011

Purpose Allogeneic hematopoietic cell transplantation (HCT) benefits many patients with acute myeloid leukemia (AML) in first remission. Hitherto, little attention has been given to the prognostic impact of pretransplantation minimal residual disease (MRD). Patients and Methods We retrospectively studied 99 consecutive patients receiving myeloablative HCT for AML in first morphologic remission. Ten-color multiparametric flow cytometry (MFC) was performed on bone marrow aspirates before HCT. MRD was identified as a cell population showing deviation from normal antigen expression patterns compared with normal or regenerating marrow. Any level of residual disease was considered MRD positive. Results Before HCT, 88 patients met morphologic criteria for complete remission (CR), whereas 11 had CR with incomplete blood count recovery (CRi). Twenty-four had MRD before HCT as determined by MFC. Two-year estimates of overall survival were 30.2% (range, 13.1% to 49.3%) and 76.6% (range, 64.4% to 85.1%) for MRD-positive and MRD-negative patients; 2-year estimates of relapse were 64.9% (range, 42.0% to 80.6%) and 17.6% (range, 9.5% to 27.9%). After adjustment for all or a subset of cytogenetic risk, secondary disease, incomplete blood count recovery, and abnormal karyotype pre-HCT, MRD-positive HCT was associated with increased overall mortality (hazard ratio [HR], 4.05; 95% CI, 1.90 to 8.62; P < .001) and relapse (HR, 8.49; 95% CI, 3.67 to 19.65; P < .001) relative to MRD-negative HCT. Conclusion These data suggest that pre-HCT MRD is associated with increased risk of relapse and death after myeloablative HCT for AML in first morphologic CR, even after controlling for other risk factors.
Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1
Authors: Robbins Paul F. , Morgan Richard A. , Feldman Steven A. , Yang James C. , Sherry Richard M. , Dudley Mark E. , Wunderlich John R. , Nahvi Azam V. , Helman Lee J. , Mackall Crystal L. , Kammula Udai S. , Hughes Marybeth S. , Restifo Nicholas P. , Raffeld Mark , Lee Chyi-Chia Richard , Levy Catherine L. , Li Yong F. , El-Gamil Mona , Schwarz Susan L. , Laurencot Carolyn , Rosenberg Steven A. 
Published: February 2011

Purpose Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma. Patients and Methods A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1–positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). Results Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma. Conclusion These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.
Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice
Authors: Sparks Erin E. , Perrien Daniel S. , Huppert Kari A. , Peterson Todd E. , Huppert Stacey S. 
Published: February 2011

SUMMARY
Abnormal Notch signaling in humans results in Alagille syndrome, a pleiotropic disease characterized by a paucity of intrahepatic bile ducts (IHBDs). It is not clear how IHBD paucity develops as a consequence of atypical Notch signaling, whether by a developmental lack of bile duct formation, a post-natal lack of branching and elongation or an inability to maintain formed ducts. Previous studies have focused on the role of Notch in IHBD development, and demonstrated a dosage requirement of Notch signaling for proper IHBD formation. In this study, we use resin casting and X-ray microtomography (microCT) analysis to address the role of Notch signaling in the maintenance of formed IHBDs upon chronic loss or gain of Notch function. Our data show that constitutive expression of the Notch1 intracellular domain in bi-potential hepatoblast progenitor cells (BHPCs) results in increased IHBD branches at post-natal day 60 (P60), which are maintained at P90 and P120. By contrast, loss of Notch signaling via BHPC-specific deletion of RBP-J (RBP KO), the DNA-binding partner for all Notch receptors, results in progressive loss of intact IHBD branches with age. Interestingly, in RBP KO mice, we observed a reduction in bile ducts per portal vein at P60; no further reduction had occurred at P120. Thus, bile duct structures are not lost with age; instead, we propose a model in which BHPC-specific loss of Notch signaling results in an initial developmental defect resulting in fewer bile ducts being formed, and in an acquired post-natal defect in the maintenance of intact IHBD architecture as a result of irresolvable cholestasis. Our studies reveal a previously unappreciated role for Notch signaling in the post-natal maintenance of an intact communicating IHBD structure, and suggest that liver defects observed in Alagille syndrome patients might be more complex than bile duct paucity.
A systematic review of lung-sparing extirpative surgery for pleural mesothelioma
Authors: Teh Elaine , Fiorentino Francesca , Tan Carol , Treasure Tom 
Published: February 2011

Summary Objectives There is a resurgence of interest in lung-sparing extirpative surgery for malignant pleural mesothelioma with recent reports of better survival and fewer adverse consequences than with extrapleural pneumonectomy. However, these operations are not well-characterized and to offer evidence-based clinical recommendations and to plan future trials a summary of what is already known is required. Design A formal literature search was performed and all recovered titles were sequentially sifted by title, abstract and full-text reading according to prespecified criteria. Papers were selected if they contained data relevant to the area of enquiry. Quantitative synthesis and textual analysis, appropriate to the material, were performed. Setting Follow-up studies of patients undergoing surgery for malignant pleural mesothelioma in specialist thoracic or cardiothoracic units. Participants Among the operated patients described in these papers, a total of 1270 patients had undergone lung-sparing surgery for mesothelioma. Results There were no randomized trials or other forms of controlled studies. From 464 titles, 26 papers contained sufficient data on 1270 patients to be included in the systematic review. Operative descriptions for all series were extracted and tabulated and variation was found in the nature of surgery within and between series, and the degree of detail with which it was described. There was more operative detail in recent papers. All available numerical data were extracted, tabulated and summarized using quantitative methods. The average survival at 1, 2, 3, 4 and 5 years was 51%, 26%, 16%, 11% and 9%, respectively. There were no data on patients’ performance status, symptomatic change, or other patient reported outcomes. Conclusions In the absence of any form of control data, no conclusions can be drawn concerning survival differences or symptomatic benefits attributable to surgery. As mesothelioma surgery is restricted to a selected minority of patients who often have multiple therapies, future research will require controlled studies with explicit definitions of the clinical and surgical intent.
Late peri-prosthetic femoral fracture as a major mode of failure in uncemented primary hip replacement
Authors: Streit M. R. , Merle C. , Clarius M. , Aldinger P. R. 
Published: February 2011

Peri-prosthetic femoral fracture after total hip replacement (THR) is associated with a poor outcome and high mortality. However, little is known about its long-term incidence after uncemented THR. We retrospectively reviewed a consecutive series of 326 patients (354 hips) who had received a CLS Spotorno replacement with an uncemented, straight, collarless tapered titanium stem between January 1985 and December 1989. The mean follow-up was 17 years (15 to 20). The occurrence of peri-prosthetic femoral fracture during follow-up was noted. Kaplan-Meier survival analysis was used to estimate the cumulative incidence of fracture. At the last follow-up, 86 patients (89 hips) had died and eight patients (eight hips) had been lost to follow-up. A total of 14 fractures in 14 patients had occurred. In ten hips, the femoral component had to be revised and in four the fracture was treated by open reduction and internal fixation. The cumulative incidence of peri-prosthetic femoral fracture was 1.6% (95% confidence interval 0.7 to 3.8) at ten years and 4.5% (95% confidence interval 2.6 to 8.0) at 17 years after the primary THR. There was no association between the occurrence of fracture and gender or age at the time of the primary replacement. Our findings indicate that peri-prosthetic femoral fracture is a significant mode of failure in the long term after the insertion of an uncemented CLS Spotorno stem. Revision rates for this fracture rise in the second decade. Further research is required to investigate the risk factors involved in the occurrence of late peri-prosthetic femoral fracture after the implantation of any uncemented stem, and to assess possible methods of prevention.
Surgical treatment of spontaneous posterior interosseous nerve palsy
Authors: Ochi K. , Horiuchi Y. , Tazaki K. , Takayama S. , Nakamura T. , Ikegami H. , Matsumura T. , Toyama Y. 
Published: February 2011

We have reviewed 38 surgically treated cases of spontaneous posterior interosseous nerve palsy in 38 patients with a mean age of 43 years (13 to 68) in order to identify clinical factors associated with its prognosis. Interfascicular neurolysis was performed at a mean of 13 months (1 to 187) after the onset of symptoms. The mean follow-up was 21 months (5.5 to 221). Medical Research Council muscle power of more than grade 4 was considered to be a good result. A further 12 cases in ten patients were treated conservatively and assessed similarly. Of the 30 cases treated surgically with available outcome data, the result of interfascicular neurolysis was significantly better in patients < 50 years old (younger group (18 nerves); good: 13 nerves (72%), poor: five nerves (28%)) than in cases > 50 years old (older group (12 nerves); good: one nerve (8%), poor: 11 nerves (92%)) (p < 0.001). A pre-operative period of less than seven months was also associated with a good result in the younger group (p = 0.01). The older group had a poor result regardless of the pre-operative delay. Our recommended therapeutic approach therefore is to perform interfascicular neurolysis if the patient is < 50 years of age, and the pre-operative delay is < seven months. If the patient is > 50 years of age with no sign of recovery for seven months, or in the younger group with a pre-operative delay of more than a year, we advise interfascicular neurolysis together with tendon transfer as the primary surgical procedure.
The effect of surface finish and interstitial fluid on the cement-in-cement interface in revision surgery of the hip
Authors: Rudol G. , Wilcox R. , Jin Z. , Tsiridis E. 
Published: February 2011

The mechanical performance of the cement-in-cement interface in revision surgery has not been fully investigated. The quantitative effect posed by interstitial fluids and roughening of the primary mantle remains unclear. We have analysed the strength of the bilaminar cement-bone interface after exposure of the surface of the primary mantle to roughening and fluid interference. The end surfaces of cylindrical blocks of cement were machined smooth (Ra = 200 nm) or rough (Ra = 5 μm) and exposed to either different volumes of water and carboxymethylcellulose (a bone-marrow equivalent) or left dry. Secondary blocks were cast against the modelled surface. Monoblocks of cement were used as a control group. The porosity of the samples was investigated using micro-CT. Samples were exposed to a single shearing force to failure. The mean failure load of the monoblock control was 5.63 kN (95% confidence interval (CI) 5.17 to 6.08) with an estimated shear strength of 36 MPa. When small volumes of any fluid or large volumes were used, the respective values fell between 4.66 kN and 4.84 kN with no significant difference irrespective of roughening (p > 0.05). Large volumes of carboxymethylcellulose significantly weakened the interface. Roughening in this group significantly increased the strength with failure loads of 2.80 kN (95% CI 2.37 to 3.21) compared with 0.86 kN (95% CI 0.43 to 1.27) in the smooth variant. Roughening of the primary mantle may not therefore be as crucial as has been previously thought in clinically relevant circumstances.