bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug interactions in palliative care – it’s more than cytochrome P450
Authors: Gaertner Jan , Ruberg Klaus , Schlesiger Grit , Frechen Sebastian , Voltz Raymond 
Published: July 2011

Objective: This study aims to identify the combination of substances with high potential for drug interactions in a palliative care setting and to provide concise recommendations for physicians. Methods: We used a retrospective systematic chart analysis of 200 consecutive inpatients. The recently developed and internationally advocated classification system OpeRational ClAssification of Drug Interactions was applied using the national database of the Federal Union of German Associations of Pharmacists. Charts of patients with potential for severe DDIs were examined manually for clinical relevance. Results: In 151 patients (75%) a total of 631 potential drug interactions were identified. Opioids (exception: methadone), non-opioids (exception: non-steroidal anti-inflammatory drugs), benzodiazepines, proton-pump inhibitors, laxatives, co-analgesics (exception: carbamazepine) and butylscopolamine were generally safe. High potential for drug interactions included combinations of scopolamine, neuroleptics, metoclopramide, antihistamines, non-steroidal anti-inflammatory drugs, (levo-) methadone, amitriptyline, carbamazepine and diuretics. The manual analyses of records from eight patients with risk for severe drug interactions provided no indicator for clinical relevance in these specific patients. Drug interactions attributed to the cytochrome pathway played a minor role (exception: carbamazepine). Conclusion: Most relevant drug interactions can be expected with: (i) drugs (inter-) acting via histamine, acetylcholine or dopamine receptors; and (ii) Non-steroidal anti-inflammatory drugs. Even in last hours of life the combination of substances (e.g. anticholinergics) may produce relevant drug interactions (e.g. delirium). Perspective: Data on the potential for drug–drug interactions in palliative case is extremely scarce, but drug interactions can be limited if a few facts are considered. A synopsis of the findings of these studies is presented as concise recommendation to minimize drug interactions.
Developing a national quality register in end-of-life care: The Swedish experience
Authors: Lundström Staffan , Axelsson Bertil , Heedman Per-Anders , Fransson Greger , Fürst Carl Johan 
Published: July 2011

Background: The complexity of end-of-life care, represented by a large number of units caring for dying patients, different types of organizations and difficulties in identification and prognostication, signifies the importance of finding ways to measure the quality of end-of-life care. Aim: To establish, test and manage a national quality register for end-of-life care. Design: Two questionnaires were developed with an attempt to retrospectively identify important aspects of the care delivered during the last week in life. An internet-based IT platform was created, enabling the physician and/or nurse responsible for the care during the last week in life to register answers online. Setting: Units caring for dying people, such as hospital wards, home care units, palliative in-patient care units and nursing facilities. Results: The register received status as a National Quality Register in 2006. More than 30,000 deaths in nursing facilities, hospital wards, palliative in-patient units and private homes were registered during 2010, representing 34% of all deaths in Sweden and 58% of the cancer deaths. Conclusions: We have shown that it is feasible to establish a national quality register in end-of-life care and collect data through a web-based system. Ongoing data analyses will show in what way this initiative can lead to improved quality of life for patients and their families. There is an ongoing process internationally to define relevant outcome measures for quality of care at the end-of-life in different care settings; the registry has a potentially important role in this development.
Comparison of Inside-Out and All-Inside Techniques for the Repair of Isolated Meniscal Tears
Authors: Grant John A. , Wilde Jeff , Miller Bruce S. , Bedi Asheesh 
Published: July 2011

Background: Arthroscopic meniscal repair techniques are continuing to evolve. Most studies to date comparing the healing rate of inside-out to all-inside meniscal repair techniques are confounded by associated anterior cruciate ligament reconstruction or deficiency. Purpose: This review was conducted to compare the effectiveness and complications of the inside-out repair technique to that of the all-inside repair technique in isolated unstable peripheral longitudinal (“bucket-handle”) meniscal tears. Study Design: Systematic review. Methods: Computerized keyword searches of MEDLINE, EMBASE, CINAHL, ACP Journal Club, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were performed. Two reviewers independently performed searches and article reduction. Studies that included stratified data for isolated unstable longitudinal meniscal tears in stable knees, repaired with either an inside-out or all-inside repair technique, were selected. Data on clinical failure, subjective outcome measures, and complications were summarized. Results: Nineteen studies included data specific to isolated meniscal tears. The rate of clinical failure was 17% for inside-out repairs and 19% for all-inside repairs. Lysholm scores and Tegner activity scores were similar between the 2 repair methods (87.8 vs 90.2 and 5.6 vs 5.5, respectively). The prevalence of nerve injury/irritation was higher with the inside-out technique (9% vs 2%). All-inside techniques had a higher rate of local soft tissue irritation, swelling, and implant migration or breakage. The use of older generation, rigid, all-inside implants is associated with chondral injury. Conclusion: There are no differences in clinical failure rate or subjective outcome between inside-out and all-inside meniscus repair techniques. Complications are associated with both techniques. More nerve symptoms are associated with the inside-out repair and more implant-related complications are associated with the all-inside technique. Clinical Relevance: Rates of structural healing and complications are comparable for inside-out and all-inside repair techniques for isolated meniscal injury. Differences in observed healing rates after meniscal repair may be more dependent on tear pattern and associated anterior cruciate ligament reconstruction rather than an inside-out versus all-inside surgical approach.
Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design
Authors: Levin Bruce , Thompson John LP , Chakraborty Bibhas , Levy Gilberto , MacArthur Robert , Haley E Clarke 
Published: July 2011

Background TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. Purpose (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. Methods In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Results Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Limitations Design complexity and evolving regulatory requirements lengthened the review process. Conclusions (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.
Predicting survival in malignant mesothelioma
Authors: Musk A.W. , Olsen N. , Alfonso H. , Reid A. , Mina R. , Franklin P. , Sleith J. , Hammond N. , Threlfall T. , Shilkin K.B. , de Klerk N.H. 
Published: July 2011

Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs.Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis.Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2–1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1–1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0–198), 177 (48–350), 221 (97–504), 238 (108–502) and 301 (134–611) days; ∼4 weeks of this apparent improvement can be attributed to earlier diagnosis.With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.
Genetic variants associated with severe pneumonia in A/H1N1 influenza infection
Authors: Zúñiga J. , Buendía-Roldán I. , Zhao Y. , Jiménez L. , Torres D. , Romo J. , Ramírez G. , Cruz A. , Vargas-Alarcon G. , Sheu C-C. , Chen F. , Su L. , Tager A.M. , Pardo A. , Selman M. , Christiani D.C. 
Published: July 2011

The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility.We carried out a case–control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA).Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69–4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64–4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63–4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89–5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium.These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A,C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.
Trajectories of endurance activity following pulmonary rehabilitation in COPD patients
Authors: Soicher J.E. , Mayo N.E. , Gauvin L. , Hanley J.A. , Bernard S. , Maltais F. , Bourbeau J. 
Published: July 2011

Maintenance of physical activity following pulmonary rehabilitation remains a challenge for patients with chronic obstructive pulmonary disease (COPD). The objectives of this study were to identify patterns of endurance activity after completion of pulmonary rehabilitation and to characterise people who succeed and those who have difficulty maintaining endurance activity.In a longitudinal study embedded within a randomised clinical trial, 206 individuals with COPD underwent a 3-month pulmonary rehabilitation programme. Weekly duration of endurance activity was assessed at 4, 6, 8 and 12 months after the start of rehabilitation. Trajectory modelling was used to determine the most common patterns of activity during the post-rehabilitation phase from 4–12 months.Three distinct patterns were identified, two of which indicated difficulty in maintaining endurance activity: 61 individuals reported a high activity level at 4 months (2.7 h·week−1) and stayed high; 114 individuals started at a low activity level (mean 1.0 h·week−1) and stayed low; and 31 individuals started high (3.0 h·week−1) and declined. The low activity group was characterised by more severe disease and greater respiratory impairment. The high and declined group had less severe disease and respiratory impairment, but reported greater barriers to exercise.Pulmonary rehabilitation should include interventions aimed at minimising barriers, in order to induce long-term behaviour change.
Is community-acquired pneumonia an independent risk factor for cardiovascular disease?
Authors: Singanayagam A. , Singanayagam A. , Elder D.H.J. , Chalmers J.D. 
Published: July 2011

Community-acquired pneumonia (CAP) is the most frequent infectious cause of death in western countries. The high mortality rate in CAP is commonly related to comorbid conditions such as cardiovascular disease.Clinical studies in both primary and secondary care settings have identified an increase in short- and long-term risk of cardiovascular events and death from vascular events following acute respiratory infections. The mechanism remains to be fully established, but it has been suggested that the inflammatory state in patients affected by CAP acts to promote platelet activation and thrombosis, and to narrow coronary arteries through vasoconstriction. Acute infections destabilise vascular endothelium and create an imbalance between myocardial oxygen supply and demand, leading to an increased risk of cardiovascular events. Acute infections have been shown to have both systemic effects and local effects on coronary vessels. These effects are mediated through both the host response to infection and, in some cases, direct effects of bacterial infection or bacterial products.In this review, we discuss the link between CAP and increased risk of cardiovascular events, drawing on existing evidence from clinical and mechanistic studies. Further studies into and increased awareness of this association is warranted to promote novel ways of protecting high-risk patients.
Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients
Authors: Liu D. , Liu Q-Q. , Eyries M. , Wu W-H. , Yuan P. , Zhang R. , Soubrier F. , Jing Z-C. 
Published: July 2011

Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene predispose to pulmonary arterial hypertension (PAH). 290 idiopathic (I)PAH patients and 15 heritable (H)PAH were screened to determine the spectrum and rate ofBMPR2mutations in a large Chinese patient group.Gene sequencing and multiplex ligation-dependent probe amplification (MLPA®) were used to detect sequence mutations and large rearrangements (RGTs). Total mutation rate was 14.5% (n=42 out of 290) in Chinese IPAH patients, and 53.3% (n=8 out of 15) in HPAH patients. RGT mutation rate was 3.1% (n=7 out of 229) and represented 14% (n=7 out of 50) of all identified mutations. 25BMPR2mutations were newly identified.Patients in this study were younger than other reported PAH subjects.BMPR2mutation carriers were ∼6 yrs younger at diagnosis than noncarriers (p=0.002), but this relationship was significant only in the female group, which was larger. The proportion of females carrying aBMPR2mutation was half that of males (12.8%versus25.3%; p=0.008).Our results indicate that the overall genetics of Chinese PAH patients is similar to that of other populations, but the clinical picture differs by the precocity of the disease in the whole patient group, and the lower proportion of females found to carry aBMPR2mutation.
Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis
Authors: Noth I. , Zangan S.M. , Soares R.V. , Forsythe A. , Demchuk C. , Takahashi S.M. , Patel S.B. , Strek M.E. , Krishnan J.A. , Patti M.G. , MacMahon H. 
Published: July 2011

Hiatal hernia (HH) is associated with gastro-oesophageal reflux (GOR) and/or GOR disease and may contribute to idiopathic pulmonary fibrosis (IPF). We hypothesised that HH evaluated by computed tomography is more common in IPF than in asthma or chronic obstructive pulmonary disease (COPD), and correlates with abnormal GOR measured by pH probe testing.Rates of HH were compared in three cohorts, IPF (n=100), COPD (n=60) and asthma (n=24), and evaluated for inter-observer agreement. In IPF, symptoms and anti-reflux medications were correlated with diffusing capacity of the lung for carbon monoxide (DL,CO) and composite physiologic index (CPI). HH was correlated with pH probe testing in IPF patients (n=14).HH was higher in IPF (39%) than either COPD (13.3%, p=0.00009) or asthma (16.67%, p=0.0139). The HH inter-observer κ agreement was substantial in IPF (κ=0.78) and asthma (κ=0.86), and moderate in COPD (κ=0.42). In IPF, HH did not correlate with lung function, except in those on anti-reflux therapy, who had a betterDL,CO(p<0.03) and CPI (p<0.04). HH correlated with GOR as measured by DeMeester scores (p<0.04).HH is more common in IPF than COPD or asthma. In an IPF cohort, HH correlated with higher DeMeester scores, confirming abnormal acid GOR. Presence of HH alone was not associated with decreased lung function.
Roflumilast with long-acting β2-agonists for COPD: influence of exacerbation history
Authors: Bateman E.D. , Rabe K.F. , Calverley P.M.A. , Goehring U.M. , Brose M. , Bredenbröker D. , Fabbri L.M. 
Published: July 2011

The oral, selective phosphodiesterase type-4 inhibitor roflumilast reduces exacerbations and improves lung function in patients with severe-to-very severe chronic obstructive pulmonary disease (COPD).We investigated the efficacy and safety of roflumilast used concomitantly with long-acting β2-agonists (LABAs) to reduce exacerbations, and the influence of exacerbation history. Pooled data were analysed from two 12-month, placebo-controlled roflumilast (500 μg once daily) studies involving 3,091 patients with severe-to-very severe COPD.Approximately half of patients used concomitant LABAs; 39% used concomitant short-acting muscarinic antagonists (SAMAs); 27% were frequent exacerbators (two or more exacerbations per year). Roflumilast reduced the rate of moderate or severe exacerbations, with LABA (rate ratio (RR) 0.79, 95% CI 0.69–0.91; p=0.001) or without LABA (RR 0.85, 95% CI 0.74–0.99; p=0.039) and prolonged time both to first (p=0.035 with LABA, p=0.300 without LABA) and second (p=0.018 with LABA, p=0.049 without LABA) exacerbations. Frequent exacerbators experienced a reduction in moderate or severe exacerbations (RR 0.78, 95% CI 0.66–0.91; p=0.002). Similarly, roflumilast remained effective with concomitant SAMA. No differences arose in adverse events between these subgroups.Roflumilast may be used to reduce exacerbations and improve dyspnoea and lung function, without increasing adverse events in COPD patients receiving concomitant LABAs.
Targeted gene delivery ofBMPR2attenuates pulmonary hypertension
Authors: Reynolds A.M. , Holmes M.D. , Danilov S.M. , Reynolds P.N. 
Published: July 2011

Pulmonary arterial hypertension (PAH) remains a fatal disease despite modern pharmacotherapy. Mutations in the gene for bone morphogenetic protein receptor type II (BMPR2) lead to reduced BMPR2 expression, which is causally linked to PAH. BMPR2 is predominantly expressed on pulmonary endothelium and has complex interactions with transforming growth factor (TGF)-β signalling mechanisms.Our objectives were to assess the effect on PAH of upregulatingBMPR2by targeted adenoviralBMPR2gene delivery to the pulmonary vascular endothelium. We used two established rat models of PAH: chronic hypoxia and monocrotaline (MCT).In both hypertensive models, those receivingBMPR2had less right ventricular hypertrophy, less pulmonary vascular resistance, improved cardiac function and reduced vascular remodelling. In the MCT model, there was an increase in TGF-β, which was prevented byBMPR2treatment.In vitro, TGF-β1-induced endothelial–mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells, which was associated with reduced BMPR2 expression. EndMT was partially ameliorated by stimulating BMPR2 signalling with appropriate ligands even in the ongoing presence of TGF-β1.Collectively, these results indicate therapeutic potential for upregulation of theBMPR2axis in PAH, which may be, in part, mediated by countering the remodelling effects of TGF-β.
Tuberculosis and HIV co-infection in European Union and European Economic Area countries
Authors: Pimpin L. , Drumright L.N. , Kruijshaar M.E. , Abubakar I. , Rice B. , Delpech V. , Hollo V. , Amato-Gauci A. , Manissero D. , Ködmön C. 
Published: July 2011

In order to ensure the availability of resources for tuberculosis (TB) and HIV management and control, it is imperative that countries monitor and plan for co-infection in order to identify, treat and prevent TB–HIV co-infection, thereby reducing TB burden and increasing the years of healthy life of people living with HIV.A systematic review was undertaken to determine the burden of TB–HIV infection in the European Union (EU) and European Economic Area (EEA). Data on the burden of HIV infection in TB patients and risk factors for TB–HIV co-infection in the EU/EEA were extracted from studies that collected information in 1996 and later, regardless of the year of initiation of data collection, and a narrative synthesis presented.The proportion of HIV-co-infected TB patients varied from 0 to 15%. Western and eastern countries had higher levels and increasing trends of infection over time compared with central EU/EEA countries. Groups at higher risk of TB–HIV co-infection were males, young adults, foreign-born persons, the homeless, injecting drug users and prisoners.Further research is needed into the burden and associated risk factors of co-infection in Europe, to help plan effective control measures. Increased HIV testing of TB patients and targeted and informed strategies for control and prevention could help curb the co-infection epidemic.