bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian models for subgroup analysis in clinical trials
Authors: Jones Hayley E , Ohlssen David I , Neuenschwander Beat , Racine Amy , Branson Michael 
Published: February 2011

Background In a pharmaceutical drug development setting, possible interactions between the treatment and particular baseline clinical or demographic factors are often of interest. However, the subgroup analysis required to investigate such associations remains controversial. Concerns with classical hypothesis testing approaches to the problem include low power, multiple testing, and the possibility of data dredging. Purpose As an alternative to hypothesis testing, the use of shrinkage estimation techniques is investigated in the context of an exploratory post hoc subgroup analysis. A range of models that have been suggested in the literature are reviewed. Building on this, we explore a general modeling strategy, considering various options for shrinkage of effect estimates. This is applied to a case-study, in which evidence was available from seven-phase II–III clinical trials examining a novel therapy, and also to two artificial datasets with the same structure. Methods Emphasis is placed on hierarchical modeling techniques, adopted within a Bayesian framework using freely available software. A range of possible subgroup model structures are applied, each incorporating shrinkage estimation techniques. Results The investigation of the case-study showed little evidence of subgroup effects. Because inferences appeared to be consistent across a range of well-supported models, and model diagnostic checks showed no obvious problems, it seemed this conclusion was robust. It is reassuring that the structured shrinkage techniques appeared to work well in a situation where deeper inspection of the data suggested little evidence of subgroup effects. Limitations The post hoc examination of subgroups should be seen as an exploratory analysis, used to help make better informed decisions regarding potential future studies examining specific subgroups. To a certain extent, the degree of understanding provided by such assessments will be limited by the quality and quantity of available data. Conclusions In light of recent interest by health authorities into the use of subgroup analysis in the context of drug development, it appears that Bayesian approaches involving shrinkage techniques could play an important role in this area. Hopefully, the developments outlined here provide useful methodology for tackling such a problem, in-turn leading to better informed decisions regarding subgroups.
The effects of growth and differentiation factor 5 on bone marrow stromal cell transplants in an in vitro tendon healing model
Authors: Hayashi M. , Zhao C. , An K.-N. , Amadio P. C. 
Published: February 2011

The effects of growth differentiation factor-5 (GDF-5) and bone marrow stromal cells (BMSCs) on tendon healing were investigated under in vitro tissue culture conditions. BMSCs and GDF-5 placed in a collagen gel were interpositioned between the cut ends of dog flexor digitorum profundus tendons. The tendons were randomly assigned into four groups: 1) repaired tendon without gel; 2) repaired tendon with BMSC-seeded gel; 3) repaired tendon with GDF-5 gel without cells; and 4) repaired tendon with GDF-5 treated BMSC-seeded gel. At 2 and 4 weeks, the maximal strength of repaired tendons with GDF-5 treated BMSCs-seeded gel was significantly higher than in tendons without gel interposition. However, neither BMSCs nor GDF-5 alone significantly increased the maximal strength of healing tendons at 2 or 4 weeks. These results suggest that the combination of BMSCs and GDF-5 accelerates tendon healing, but either BMSCs or GDF-5 alone are not effective in this model.
Kirschner wire fixation for scaphoid fractures: an experimental study in synthetic bones
Authors: Gokce V. , Oflaz H. , Dulgeroglu A. , Bora A. , Gunal I. 
Published: February 2011

We have studied the biomechanical stability in vitro of three different Kirschner (K) wire configurations in three types of simulated scaphoid waist fractures. The fractures were created with a saw in Sawbones models. There were three fracture patterns: perpendicular to the long axis of the scaphoid model; and 30° and 20° oblique to that. Two 1.2 mm. K-wires were used in each scaphoid. The three configurations were: parallel; 20° oblique; and crossing. The oblique or crossing configurations of K-wires were the most stable depending on the fracture pattern.
The tension band principle and angular testing of extensor tendon repairs
Authors: Henderson J. , Sutcliffe M. , Gillespie P. 
Published: February 2011

Extensor tendons in the finger are flat and not amenable to repair by core and epitendinous sutures. Mattress sutures and Kessler repairs without epitendinous stitching are often used for extensor tendon divisions in the fingers. Except when in full extension, the finger presents a series of curved surfaces (at each joint) to the tendon. It was hypothesized that extensor tendons are subject to the ‘tension band’ principle and that they might be amenable to repair by dorsal-only epitendinous sutures. A Silfverskiöld dorsal-only repair was compared with mattress and Kessler repairs in vitro on a curvilinear testing apparatus. The epitendinous technique was found to be significantly more resistant to gapping and rupture, as well as more resistant to deformation (i.e. stiffer) than the conventional techniques.
Impact of inspiratory muscle training in patients with COPD: what is the evidence?
Authors: Gosselink R. , De Vos J. , van den Heuvel S.P. , Segers J. , Decramer M. , Kwakkel G. 
Published: February 2011

A meta-analysis including 32 randomised controlled trials on the effects of inspiratory muscle training (IMT) in chronic obstructive pulmonary disease (COPD) patients was performed. Overall and subgroup analyses with respect to training modality (strength or endurance training, added to general exercise training) and patient characteristics were performed. Significant improvements were found in maximal inspiratory muscle strength (PI,max; +13 cmH2O), endurance time (+261 s), 6- or 12-min walking distance (+32 and +85 m respectively) and quality of life (+3.8 units). Dyspnoea was significantly reduced (Borg score -0.9 point; Transitional Dyspnoea Index +2.8 units). Endurance exercise capacity tended to improve, while no effects on maximal exercise capacity were found. Respiratory muscle endurance training revealed no significant effect onPI,max, functional exercise capacity and dyspnoea. IMT added to a general exercise programme improvedPI,maxsignificantly, while functional exercise capacity tended to increase in patients with inspiratory muscle weakness (PI,max<60 cmH2O).IMT improves inspiratory muscle strength and endurance, functional exercise capacity, dyspnoea and quality of life. Inspiratory muscle endurance training was shown to be less effective than respiratory muscle strength training. In patients with inspiratory muscle weakness, the addition of IMT to a general exercise training program improvedPI,maxand tended to improve exercise performance.
Circulating endothelial progenitor cells and chronic pulmonary diseases
Authors: Huertas A. , Palange P. 
Published: February 2011

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular healing and remodelling under physiological and pathological conditions. Although controversies exist regarding the definition and origin of EPCs, it has been widely demonstrated that they are involved in several diseases and that they have therapeutic implications.Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation that is not fully reversible, associated with abnormalities of airways (bronchitis) and parenchyma (emphysema), reduced exercise tolerance and systemic inflammation.Growing evidence has also suggested that endothelial dysfunction may play a role in COPD. Although it is not clear whether endothelial dysfunction represents a cause or a consequence of COPD, several studies have highlighted the importance of EPCs in this disease, suggesting that the bone marrow could be a novel target of COPD.The present review summarises the role of EPCs in pulmonary diseases, with particular emphasis on COPD. The aim is to improve understanding as to the possible role of EPCs in COPD pathophysiology. This may help in the identification of novel diagnostic and therapeutic tools in COPD.
Blockade of Th1 chemokine receptors ameliorates pulmonary granulomatosis in mice
Authors: Kishi J. , Nishioka Y. , Kuwahara T. , Kakiuchi S. , Azuma M. , Aono Y. , Makino H. , Kinoshita K. , Kishi M. , Batmunkh R. , Uehara H. , Izumi K. , Sone S. 
Published: February 2011

Sarcoidosis is a granulomatous disease of unknown aetiology. We identified immunological targets for the treatment of pulmonary granulomatosis using a murine model generated withPropionibacterium acnes.Sensitisation and challenge using heat-killedP. acnesand dendritic cells (DCs) were performed to produce pulmonary granulomatosis in C57BL/6 mice. Immunological analyses using ELISA as well as cDNA microarray analysis were used to search for cytokines or chemokines associated with the formation of granulomas in the lungs.Co-administration ofP. acnesand DCs reproducibly induced the formation of pulmonary granulomas, which resembled sarcoid granulomas. The cDNA microarray assay demonstrated that the gene expression of CXCL9 and CXCL10, ligands for CXCR3, and of CCL4, a ligand for CCR5, was strongly upregulated during granulomatosis. ELISA confirmed that levels of CXCL9 and CXCL10 as well as T-helper (Th)1 cytokines and chemokines including tumour necrosis factor-α and interferon-γ were elevated in bronchoalveolar lavage fluid (BALF). The blockade of Th1 chemokine receptors using TAK-779, a dual blocker for CXCR3 and CCR5, led to reduced numbers of CXCR3+CD4+ and CCR5+CD4+ T-cells in BALF. Furthermore, administration of TAK-779 ameliorated the granulomatosis.The targeted inhibition of Th1 chemokines might be useful for inhibiting Th1-biased granulomatous diseases, including sarcoidosis.
The Movement for Global Mental Health
Authors: Patel Vikram , Collins Pamela Y. , Copeland John , Kakuma Ritsuko , Katontoka Sylvester , Lamichhane Jagannath , Naik Smita , Skeen Sarah 
Published: February 2011

SummaryThe Movement for Global Mental Health is a coalition of individuals and institutions committed to collective actions that aim to close the treatment gap for people living with mental disorders worldwide, based on two fundamental principles: evidence on effective treatments and the human rights of people with mental disorders.
Quantifying the effect of early retirement on the wealth of individuals with depression or other mental illness
Authors: Schofield Deborah J. , Shrestha Rupendra N. , Percival Richard , Kelly Simon J. , Passey Megan E. , Callander Emily J. 
Published: February 2011

BackgroundIn addition to the health burden caused by mental illnesses, these conditions contribute to economic disadvantage because of their impact on labour force participation.AimsTo quantify the cost of lost savings and wealth to Australians aged 45–64 who retire from the labour force early because of depression or other mental illness.MethodCross-sectional analysis of the base population of Health&WealthMOD, a microsimulation model built on data from the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers and STINMOD, an income and savings microsimulation model.ResultsPeople who are not part of the labour force because of depression or other mental illness have 78% (95% CI 92.2–37.1) and 93% (95% CI 98.4–70.5) less wealth accumulated respectively, compared with people of the same age, gender and education who are in the labour force with no chronic health condition. People who are out of the labour force as a result of depression or other mental illness are also more likely to have the wealth that they do have in cash assets, rather than higher-growth assets such as superannuation, home equity and other financial investments.ConclusionsThis lower accumulated wealth is likely to result in lower living standards for these individuals in the future. This will compound the impact of their condition on their health and quality of life, and put a large financial burden on the state as a result of the need to provide financial assistance for these individuals.
Overcrowding in psychiatric wards and physical assaults on
staff: data-linked longitudinal study
Authors: Virtanen Marianna , Vahtera Jussi , Batty G. David , Tuisku Katinka , Pentti Jaana , Oksanen Tuula , Salo Paula , Ahola Kirsi , Kivimäki Mika 
Published: February 2011

BackgroundPatient overcrowding and violent assaults by patients are two major
problems in psychiatric healthcare. However, evidence of an association
between overcrowding and aggressive behaviour among patients is mixed and
limited to small-scale studies.AimsThis study examined the association between ward overcrowding and violent
physical assaults in acute-care psychiatric in-patient hospital
wards.MethodLongitudinal study using ward-level monthly records of bed occupancy and
staff reports of the timing of violent acts during a 5-month period in 90
in-patient wards in 13 acute psychiatric hospitals in Finland. In total
1098 employees (physicians, ward head nurses, registered nurses, licensed
practical nurses) participated in the study. The outcome measure was
staff reports of the timing of physical assaults on both themselves and
ward property.ResultsWe found that 46% of hospital staff were working in overcrowded wards, as
indicated by >10 percentage units of excess bed occupancy, whereas
only 30% of hospital personnel were working in a ward with no excess
occupancy. An excess bed occupancy rate of >10 percentage units at the
time of an event was associated with violent assaults towards employees
(odds ratio (OR) = 1.72, 95% CI 1.05–2.80; OR = 3.04, 95% CI 1.51–6.13 in
adult wards) after adjustment for confounding factors. No association was
found with assaults on ward property (OR = 1.06, 95% CI 0.75–1.50).ConclusionsThese findings suggest that patient overcrowding is highly prevalent in
psychiatric hospitals and, importantly, may increase the risk of violence
directed at staff.
Life stress, 5-HTTLPR and mental disorder: findings from a 30-year longitudinal study
Authors: Fergusson David M. , Horwood L. John , Miller Allison L. , Kennedy Martin A. 
Published: February 2011

BackgroundRecent meta-analyses have raised concerns about the replicability of gene × environment interactions involving the serotonin transporter gene (5-HTTLPR) in moderating the associations between adverse life events and mental disorders.AimsTo use data gathered over the course of a 30-year longitudinal study of a New Zealand birth cohort to test the hypothesis that the presence of short (‘s’) alleles of 5-HTTLPR are associated with an increased response to life stress.MethodParticipants were 893 individuals from the Christchurch Health and Development Study who had complete data on: the 5-HTTLPR genotype; psychiatric disorders up to the age of 30; and exposure to childhood and adult adverse life events.ResultsA series of 104 regression models were fitted to four mental health outcomes (depressive symptoms, major depression, anxiety disorder and suicidal ideation) observed at ages 18, 21, 25 and 30 using 13 measures of life-course stress that spanned childhood and adult stressors. Both multiplicative and additive models were fitted to the data. No evidence was found that would support the hypothesis that ‘s' alleles of 5-HTTLPR are associated with increased responsivity to life stressors.ConclusionsThe present findings add to the evidence suggesting that it is unlikely that there is a stable gene × environment interaction involving 5-HTTLPR, life stress and mental disorders.
Patients repeatedly attending accident and emergency departments seeking psychiatric care
Authors: Okorie Eugene F. , McDonald Colm , Dineen Brendan 
Published: February 2011

Aims and methodThis study was conducted to ascertain the clinical characteristics of patients who repeatedly attend accident and emergency (A&E) department seeking psychiatric assessment and care. We identified 24 individuals who attended frequently and compared them with 72 matched single attenders using data abstracted by chart review.ResultsIndividuals who attended frequently made up 5.3% of all patients who attended the A&E department for psychiatric care but accounted for 19% of all such presentations. Compared with controls, they were younger at first psychiatric contact and had higher rates of schizophrenia and psychiatric admissions.Clinical implicationsA small but distinctive group of patients repeatedly seek and obtain hospital-based psychiatric care. Early identification of these patients and targeting them with effective, community-oriented strategies, such as home treatment, could improve their quality of life and prognoses as well as reduce the cost of their care.
Improving physical health monitoring in secondary care for patients on clozapine
Authors: Bolton Philipp J. 
Published: February 2011

Aims and methodTo assess how well psychiatric teams follow up abnormal results from physical health monitoring of patients in a secondary care clozapine clinic compared with follow-up in a specialist secondary care physical health clinic, using an audit/re-audit method of comparison. Prevalence data for cardiovascular risk factors within the clinic population were also obtained.ResultsSubstantial and statistically significant (P < 0.01) improvements in follow-up of abnormal results were made following the introduction of a specialist clinic compared with treatment as usual. Prevalence of all cardiovascular risk factors among the patients on clozapine was very high compared with the general population.Clinical implicationsPatients on clozapine have significant and multiple cardiovascular risk factors, which may be best managed within a specialist secondary care physical health clinic that can follow up abnormal results and coordinate care across primary and secondary care.
‘Happiness-deficit disorder’? Prevention is better than cure
Authors: Kelly Brendan D. 
Published: February 2011

SummaryBeing happy is associated not only with better health, higher earnings and a longer life, but also with a stable family upbringing, stable financial situation, employment, good health, freedom and personal values. Psychiatrists may increase their patients' happiness by promoting effective, evidence-based mental healthcare. Individuals may enhance their own happiness by optimising physical and mental health; recognising the importance of personal values and happy communities; and optimising their financial situation. Government may boost citizens' happiness by deepening democracy; providing effective healthcare; supporting evidence-based well-being initiatives in communities; and then leaving citizens to seek out personal happiness in their own way.
Vandetanib Plus Pemetrexed for the Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer: A Randomized, Double-Blind Phase III Trial
Authors: de Boer Richard H. , Arrieta Óscar , Yang Chih-Hsin , Gottfried Maya , Chan Valorie , Raats Johann , de Marinis Filippo , Abratt Raymond P. , Wolf Jürgen , Blackhall Fiona H. , Langmuir Peter , Milenkova Tsveta , Read Jessica , Vansteenkiste Johan F. 
Published: February 2011

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This randomized, placebo-controlled phase III study assessed the efficacy of vandetanib plus pemetrexed as second-line therapy in advanced non–small-cell lung cancer. Patients and Methods Patients (N = 534) were randomly assigned to receive vandetanib 100 mg/d plus pemetrexed 500 mg/m2 every 21 days (n = 256) or placebo plus pemetrexed (n = 278). Progression-free survival (PFS) was the primary end point; overall survival, objective response rate, disease control rate, time to deterioration of symptoms, and safety were secondary assessments. Results There was no significant difference in PFS between treatment arms (hazard ratio [HR], 0.86; 97.58% CI, 0.69 to 1.06; P = .108). Overall survival was also not significantly different (HR, 0.86; 97.54% CI, 0.65 to 1.13; P = .219). Statistically significant improvements in objective response rate (19% v 8%; P < .001) and time to deterioration of symptoms (HR, 0.71; P = .0052; median, 18.1 weeks for vandetanib and 12.1 weeks for placebo) were observed in patients receiving vandetanib. Adding vandetanib to pemetrexed increased the incidence of some adverse events, including rash, diarrhea, and hypertension, while showing a reduced incidence of nausea, vomiting, anemia, fatigue, and asthenia with no reduction in the dose intensity of pemetrexed. Conclusion This study did not meet the primary end point of statistically significant PFS prolongation with vandetanib plus pemetrexed versus placebo plus pemetrexed. The vandetanib combination showed a significantly higher objective response rate and a significant delay in the time to worsening of lung cancer symptoms versus the placebo arm as well as an acceptable safety profile in this patient population.
Enhancing Patient-Provider Communication With the Electronic Self-Report Assessment for Cancer: A Randomized Trial
Authors: Berry Donna L. , Blumenstein Brent A. , Halpenny Barbara , Wolpin Seth , Fann Jesse R. , Austin-Seymour Mary , Bush Nigel , Karras Bryant T. , Lober William B. , McCorkle Ruth 
Published: February 2011

Purpose Although patient-reported cancer symptoms and quality-of-life issues (SQLIs) have been promoted as essential to a comprehensive assessment, efficient and efficacious methods have not been widely tested in clinical settings. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment–Cancer (ESRA-C) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits. Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians. Patients and Methods This randomized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center. Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit (n = 327); in the control group, no summary was provided (n = 333). SQLIs were scored for level of severity or distress. One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI. We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians. Results The likelihood of SQLIs being discussed differed by randomized group and depended on whether an SQLI was first reported as problematic (P = .032). Clinic visits were similar with regard to duration between groups, and clinicians reported the summary as useful. Conclusion The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US randomized clinical trial.