bluuebunny/crossref_metadata_2025_split huggingface dataset:
F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis
Authors: Gouw Samantha C. , van den Berg H. Marijke , Oldenburg Johannes , Astermark Jan , de Groot Philip G. , Margaglione Maurizio , Thompson Arthur R. , van Heerde Waander , Boekhorst Jorien , Miller Connie H. , le Cessie Saskia , van der Bom Johanna G. 
Published: January 2012

AbstractThis systematic review was designed to provide more precise effect estimates of inhibitor development for the various types of F8 gene mutations in patients with severe hemophilia A. The primary outcome was inhibitor development and the secondary outcome was high-titer-inhibitor development. A systematic literature search was performed to include cohort studies published in peer-reviewed journals with data on inhibitor incidences in the various F8 gene mutation types and a mutation detection rate of at least 80%. Pooled odds ratios (ORs) of inhibitor development for different types of F8 gene mutations were calculated with intron 22 inversion as the reference. Data were included from 30 studies on 5383 patients, including 1029 inhibitor patients. The inhibitor risk in large deletions and nonsense mutations was higher than in intron 22 inversions (pooled OR = 3.6, 95% confidence interval [95% CI], 2.3-5.7 and OR = 1.4, 95% CI, 1.1-1.8, respectively), the risk in intron 1 inversions and splice-site mutations was equal (pooled OR = 0.9; 95% CI, 0.6-1.5 and OR = 1.0; 95% CI, 0.6-1.5), and the risk in small deletions/insertions and missense mutations was lower (pooled OR = 0.5; 95% CI, 0.4-0.6 and OR = 0.3; 95% CI, 0.2-0.4, respectively). The relative risks for developing high titer inhibitors were similar.
Plasma biomarkers of lower gastrointestinal and liver acute GVHD
Authors: Harris Andrew C. , Ferrara James L. M. , Braun Thomas M. , Holler Ernst , Teshima Takanori , Levine John E. , Choi Sung W. , Landfried Karin , Akashi Koichi , Lugt Mark Vander , Couriel Daniel R. , Reddy Pavan , Paczesny Sophie 
Published: January 2012

Abstract
The lower gastrointestinal tract (LGI) and liver are the GVHD target organs most associated with treatment failure and nonrelapse mortality. We recently identified regenerating islet-derived 3-α (REG3α) as a plasma biomarker of LGI GVHD. We compared REG3α with 2 previously reported GI and liver GVHD diagnostic biomarkers, hepatocyte growth factor (HGF) and cytokeratin fragment 18, in 954 hematopoietic cell transplantation patients. All 3 biomarkers were significantly elevated in LGI GVHD compared with non-GVHD diarrhea; REG3α discerned LGI GVHD from non-GVHD diarrhea better than HGF and cytokeratin fragment 18. Although all 3 biomarkers predicted nonresponse to therapy at day 28 in LGI GVHD patients, only REG3α and HGF concentrations predicted 1-year nonrelapse mortality (P = .01 and P = .02, respectively). Liver GVHD without GI involvement at GVHD onset and non-GVHD liver complications were uncommon; all 3 biomarkers were elevated in liver GVHD, but did not distinguish GVHD from other causes of hyperbilirubinemia.
Management of primary ciliary dyskinesia in European children: recommendations and clinical practice
Authors: Strippoli Marie-Pierre F. , Frischer Thomas , Barbato Angelo , Snijders Deborah , Maurer Elisabeth , Lucas Jane S.A. , Eber Ernst , Karadag Bulent , Pohunek Petr , Zivkovic Zorica , Escribano Amparo , O’Callaghan Chris , Bush Andrew , Kuehni Claudia E. 
Published: January 2012

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe.Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2–9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country’s general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments.In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.
Pregnancy outcomes in pulmonary arterial hypertension in the modern management era
Authors: Jaïs Xavier , Olsson Karen M. , Barbera Joan A. , Blanco Isabel , Torbicki Adam , Peacock Andrew , Vizza C. Dario , Macdonald Peter , Humbert Marc , Hoeper Marius M. 
Published: January 2012

Previous studies have reported mortality rates of up to 56% associated with pregnancy in pulmonary arterial hypertension (PAH) but the management of this disease has changed considerably in recent years.We compiled a multinational, prospective registry to examine the contemporary outcome of pregnancies in patients with PAH.During a 3-yr period, the 13 participating centres reported 26 pregnancies. Three (12%) females died and one (4%) developed right heart failure requiring urgent heart–lung transplantation. There were eight abortions; two spontaneous and six induced. 16 (62%) pregnancies were successful,i.e.the females delivered healthy babies without complications. These females had well controlled PAH (pulmonary vascular resistance (PVR) 500±352 dyn·s·cm−5); eight of them were long-term responders to calcium channel blockers. In contrast, the females who died or required transplantation had poorly controlled PAH (PVR 1,667±209 dyn·s·cm−5).Pregnancy remains associated with a substantial mortality rate in PAH. However, our results indicate that the outcome of pregnancy in PAH has improved, at least when PAH is well controlled, and particularly in long-term responders to calcium channel blockers. These data must be confirmed by larger series before the general recommendation to avoid pregnancy in all patients with PAH is reconsidered.
The chronic bronchitis phenotype in subjects with and without COPD: the PLATINO study
Authors: de Oca Maria Montes , Halbert Ronald J. , Lopez Maria Victorina , Perez-Padilla Rogelio , Tálamo Carlos , Moreno Dolores , Muiño Adrianna , Jardim José Roberto B. , Valdivia Gonzalo , Pertuzé Julio , Menezes Ana Maria B. 
Published: January 2012

Little information exists regarding the epidemiology of the chronic bronchitis phenotype in unselected chronic obstructive pulmonary disease (COPD) populations. We examined the prevalence of the chronic bronchitis phenotype in COPD and non-COPD subjects from the PLATINO study, and investigated how it is associated with important outcomes.Post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70 was used to define COPD. Chronic bronchitis was defined as phlegm on most days, at least 3 months per year for ≥2 yrs. We also analysed another definition: cough and phlegm on most days, at least 3 months per year for ≥2 yrs.Spirometry was performed in 5,314 subjects (759 with and 4,554 without COPD). The proportion of subjects with and without COPD with chronic bronchitis defined as phlegm on most days, at least 3 months per year for ≥2 yrs was 14.4 and 6.2%, respectively. Using the other definition the prevalence was lower: 7.4% with and 2.5% without COPD. Among subjects with COPD, those with chronic bronchitis had worse lung function and general health status, and had more respiratory symptoms, physical activity limitation and exacerbations.Our study helps to understand the prevalence of the chronic bronchitis phenotype in an unselected COPD population at a particular time-point and suggests that chronic bronchitis in COPD is possibly associated with worse outcomes.
Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort
Authors: Herth Felix J.F. , Noppen Marc , Valipour Arschang , Leroy Sylvie , Vergnon Jean-Michel , Ficker Joachim H. , Egan Jim J. , Gasparini Stefano , Agusti Carlos , Holmes-Higgin Debby , Ernst Armin 
Published: January 2012

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort.Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n=111) or medical management (n=60).At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean±sdchange in forced expiratory volume in 1 s (7±20%versus0.5±19%; p=0.067), cycle ergometry (2±14 Wversus-3±10 W; p=0.04) and St George’s Respiratory Questionnaire (-5±14 pointsversus0.3±13 points; p=0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean±sdlobar volume reduction of -80±30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes.Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.
Randomised controlled trial for emphysema with a selective agonist of the γ-type retinoic acid receptor
Authors: Stolk Jan , Stockley Robert A. , Stoel Berend C. , Cooper Brendan G. , Piitulainen Eeva , Seersholm Niels , Chapman Kenneth R. , Burdon Jonathan G.W. , Decramer Marc , Abboud Raja T. , Mannes Gregorius P.M. , Wouters Emiel F. , Garrett Jeffrey E. , Barros-Tizon Juan C. , Russi Erich W. , Lomas David A. , MacNee William A. , Rames Alexis 
Published: January 2012

Palovarotene is an oral γ-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement.REPAIR (Retinoid treatment of Emphysema in Patients on the α1-antitrypsin International Registry), was an investigator-initiated, double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg·day−1palovarotene given for 1 year to 262 patients with severe α1-antitrypsin deficiency and emphysema confirmed by computed tomography. Change in volume-adjusted 15th percentile point lung density from baseline in 1 year was the primary end-point; functional end-points were also regularly assessed.We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. 88% and 85% of patients completed 1 year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completers population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A nonsignificant treatment difference in most functional parameters of the lung in favour of the drug was observed over time suggesting potential pharmacological effects of palovarotene.Palovarotene 5 mg·day−1over 1 yr failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α1-antitrypsin deficiency.
Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy
Authors: Keir Gregory J. , Maher Toby M. , Hansell David M. , Denton Christopher P. , Ong Voon H. , Singh Suveer , Wells Athol U. , Renzoni Elisabetta A. 
Published: January 2012

In very severe interstitial lung disease associated with connective tissue disease (CTD-ILD), progressing despite maximal conventional immunosuppression, there is no effective medical rescue therapy.The aim of the present study was to test whether rituximab, a monoclonal antibody that depletes peripheral B lymphocytes, is effective as rescue therapy in very severe CTD-ILD, unresponsive to conventional immunosuppression.We performed a retrospective assessment of eight patients with severe and progressive CTD-ILD treated with rituximab. In six patients, change in pulmonary function tests (PFTs) compared with pre-rituximab levels, was assessed at 9–12 months post-treatment. In two patients, who were mechanically ventilated at the time of treatment, clinical and HRCT changes were assessed.Seven out of eight patients had a favourable treatment response to rituximab, while in one patient disease severity did not change. In contrast with previous progression, we observed a median significant improvement of 22% in diffusing capacity for carbon monoxide (from a median baseline of 25%; range 16–32%; p=0.04), and a median significant improvement of 18% in forced vital capacity (from a median baseline of 45%; range 37–59%; p=0.03), in the 9–12 months following treatment with rituximab.In very severe CTD-ILD unresponsive to conventional immunosuppression, rituximab may represent an effective, potentially life-saving, therapeutic intervention.
Mesothelioma incidence projections in South East England
Authors: Riaz Sharma P. , Coupland Victoria H. , Lüchtenborg Margreet , Peake Michael D. , Møller Henrik 
Published: January 2012

We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England.We extracted data on patients diagnosed with mesothelioma (International Classification of Diseases-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods.A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter.The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and, due to the long latency period, the incidence of mesothelioma is projected to increase until the 2020s.
Airways dilate to simulated inspiratory but not expiratory manoeuvres
Authors: West Adrian R. , Thaya Needi Elangovan , Mitchell Howard W. , McFawn Peter K. , Noble Peter B. 
Published: January 2012

In a healthy human, deep inspirations produce bronchodilation of contracted airways, which probably occurs due to the transient distension of the airway smooth muscle (ASM). We hypothesised that deep expiratory manoeuvres also produce bronchodilation due to transient airway wall and ASM compression.We used porcine bronchial segments to assess the effects of deep inspirations, and maximal and partial expiration (submaximal) on airway calibre. Respiratory manoeuvres were simulated by varying transmural pressure using a hydrostatic pressure column: deep inspiration 5 to 30 cmH2O, maximal expiration 30 to -15 cmH2O, partial expiration 10 to -15 cmH2O; amidst a background of tidal oscillations, 5 to 10 cmH2O at 0.25 Hz. Changes in luminal cross-sectional area in carbachol-contracted airways were measured using video endoscopy.Deep inspirations produce an immediate bronchodilation (∼40–60%, p=0.0076) that lasts for up to 1 min (p=0.0479). In comparison, after maximal expiration there was no immediate change in airway calibre; however, a delayed bronchodilatory response was observed from 4 s after the manoeuvre (p=0.0059) and persisted for up to 3 min (p=0.0182). Partial expiration had little or no effect or airway calibre.The results observed demonstrate that the airway wall dilates to deep inspiration manoeuvres but is unresponsive to deep expiratory manoeuvres.
Long-term efficacy of psychological treatments for binge eating disorder
Authors: Hilbert Anja , Bishop Monica E. , Stein Richard I. , Tanofsky-Kraff Marian , Swenson Anne K. , Welch R. Robinson , Wilfley Denise E. 
Published: January 2012

BackgroundThe long-term efficacy of psychological treatments for binge eating disorder remains largely unknown.AimsTo examine the long-term efficacy of out-patient group cognitive–behavioural therapy (CBT) and group interpersonal psychotherapy (IPT) for binge eating disorder and to analyse predictors of long-term non-response.MethodNinety people with binge eating disorder were assessed 4 years after treatment cessation within a randomised trial (trial registration: NCT01208272).ResultsParticipants showed substantial long-term recovery, partial remission, clinically significant improvement and significant reductions in associated psychopathology, despite relapse tendencies in single secondary outcomes. Body mass index remained stable. While the IPT group demonstrated an improvement in eating disorder symptoms over the follow-up period, the CBT group reported a worsening of symptoms, but treatments did not differ at any time point.ConclusionsThe results document the long-term efficacy of out-patient CBT and IPT for binge eating disorder. Further research is warranted to elucidate the time course and mechanisms of change of these treatments for binge eating disorder.
Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study
Authors: Nicholson Timothy R. J. , Ferdinando Sumudu , Krishnaiah Ravikumar B. , Anhoury Sophie , Lennox Belinda R. , Mataix-Cols David , Cleare Anthony , Veale David M. , Drummond Lynne M. , Fineberg Naomi A. , Church Andrew J. , Giovannoni Gavin , Heyman Isobel 
Published: January 2012

BackgroundSymptoms of obsessive–compulsive disorder (OCD) have been described in neuropsychiatric syndromes associated with streptococcal infections. It is proposed that antibodies raised against streptococcal proteins cross-react with neuronal proteins (antigens) in the brain, particularly in the basal ganglia, which is a brain region implicated in OCD pathogenesis.AimsTo test the hypothesis that post-streptococcal autoimmunity, directed against neuronal antigens, may contribute to the pathogenesis of OCD in adults.MethodNinety-six participants with OCD were tested for the presence of anti-streptolysin-O titres (ASOT) and the presence of anti-basal ganglia antibodies (ABGA) in a cross-sectional study. The ABGA were tested for with western blots using three recombinant antigens; aldolase C, enolase and pyruvate kinase. The findings were compared with those in a control group of individuals with depression (n= 33) and schizophrenia (n= 17).ResultsPositivity for ABGA was observed in 19/96 (19.8%) participants with OCD compared with 2/50 (4%) of controls (Fisher's exact testP= 0.012). The majority of positive OCD sera (13/19) had antibodies against the enolase antigen. No clinical variables were associated with ABGA positivity. Positivity for ASOT was not associated with ABGA positivity nor found at an increased incidence in participants with OCD compared with controls.ConclusionsThese findings support the hypothesis that central nervous system autoimmunity may have an aetiological role in some adults with OCD. Further study is required to examine whether the antibodies concerned are pathogenic and whether exposure to streptococcal infection in vulnerable individuals is a risk factor for the development of OCD.
Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin
Authors: Carhart-Harris R. L. , Leech R. , Williams T. M. , Erritzoe D. , Abbasi N. , Bargiotas T. , Hobden P. , Sharp D. J. , Evans J. , Feilding A. , Wise R. G. , Nutt D. J. 
Published: January 2012

BackgroundPsilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences.AimsTo test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo.MethodTen healthy participants received two functional magnetic resonance imaging scans (2mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis.ResultsRobust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective wellbeing at follow-up (P<0.01).ConclusionsEvidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.