bluuebunny/crossref_metadata_2025_split huggingface dataset:
Descriptive review and evaluation of the functioning of the International Health Regulations (IHR) Annex 2
Authors: Anema Aranka , Druyts Eric , Hollmeyer Helge G , Hardiman Maxwell C , Wilson Kumanan 
Published: January 2012

Abstract

Background
The International Health Regulations (IHRs) (2005) was developed with the aim of governing international responses to public health risks and emergencies. The document requires all 194 World Health Organization (WHO) Member States to detect, assess, notify and report any potential public health emergency of international concern (PHEIC) under specific timelines. Annex 2 of the IHR outlines decision-making criteria for State-appointed National Focal Points (NFP) to report potential PHEICs to the WHO, and is a critical component to the effective functioning of the IHRs.

Methods
The aim of the study was to review and evaluate the functioning of Annex 2 across WHO-reporting States Parties. Specific objectives were to ascertain NFP awareness and knowledge of Annex 2, practical use of the tool, activities taken to implement it, its perceived usefulness and user-friendliness. Qualitative telephone interviews, followed by a quantitative online survey, were administered to NFPs between October, 2009 and February, 2010.

Results
A total of 29 and 133 NFPs participated in the qualitative and quantitative studies, respectively. Qualitative interviews found most NFPs had a strong working knowledge of Annex 2; perceived the tool to be relevant and useful for guiding decisions; and had institutionalized management, legislation and communication systems to support it. NFPs also perceived Annex 2 as human and disease-centric, and emphasized its reduced applicability to potential PHEICs involving bioterrorist attacks, infectious diseases among animals, radio-nuclear and chemical spills, and water- or food-borne contamination. Among quantitative survey respondents, 88% reported having excellent/good knowledge of Annex 2; 77% reported always/usually using Annex 2 for assessing potential PHEICs; 76% indicated their country had some legal, regulatory or administrative provisions for using Annex 2; 95% indicated Annex 2 was always/usually useful for facilitating decisions regarding notifiability of potential PHEICs.

Conclusion
This evaluation, including a large sample of WHO-reporting States Parties, found that the IHR's Annex 2 is perceived as useful for guiding decisions about notifiability of potential PHEICs. There is scope for the WHO to expand training and guidance on application of the IHR's Annex 2 to specific contexts. Continued monitoring and evaluation of the functioning of the IHR is imperative to promoting global health security.
Adult gaucher disease in southern Tunisia: report of three cases
Authors: Ben Rhouma Faten , Kallel Faten , Kefi Rym , Cherif Wafa , Nagara Majdi , Azaiez Hela , Jedidi Ines , Elloumi Moez , Abdelhak Sonia , Mseddi Sondes 
Published: January 2012

Abstract

Background
Gaucher disease (GD) is the most frequent lysosomal storage disorder; type 1 is by far the most common form. It is characterized by variability in age of onset, clinical signs and progression. It is usually diagnosed in the first or second decade of life with the appearance of bone pains, splenomegaly and thrombocytopenia, but the disease may be diagnosed at any age between 1 and 73 years. In the present study, we report 3 cases with late onset of GD in whom the disease was a surprise finding including one patient with Parkinson disease. This late onset is described as an adult form of Gaucher disease.

Findings
Molecular investigation showed mutational homogeneity in Tunisian adult patients suffering from GD. Indeed, all patients carry the p.N370S mutation: two patients at a homozygous state and one patient at compound heterozygous state.

Conclusion
The p.N370S mutation presents a large variability in the onset of the disease and its clinical manifestation supporting the view that GD should be considered as a continuum phenotype rather than a predefined classification.

Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1701276661617840.
Responsiveness of a patient in a persistent vegetative state after a coma to weekly injections of autologous activated immune cells: a case report
Authors: Fellerhoff Barbara , Laumbacher Barbara , Wank Rudolf 
Published: January 2012

AbstractIntroductionAn 82-year-old Caucasian woman had remained in a persistent vegetative state after a coma of seven months duration, which occurred after a stroke with hemiplegia, nine years previously. The persistent vegetative state could be reversed in part by weekly injections with activated immune cells. After therapy, our patient responded to commands in addition to regaining spontaneous movements of both arms and the ability to swallow. This is the first report on the treatment with activated immune cells of a patient in a persistent vegetative state after a coma.Case presentationAn 82-year-old Caucasian woman presented with a persistent vegetative state subsequent to a coma. She retained respiratory and autonomic functions. As contact was not possible, physiotherapy was passive. Her skin was yellowish, and our patient did not move by herself. Vomiting repeatedly resulted from tube feeding. After a once-weekly treatment with activated immune cells sampled from our patient's blood and activatedin vitro, several of her functions gradually returned. Our patient opened her eyes in the requested direction and turned her head toward people entering the room. She 'supported' nursing efforts, as the nurse noted a loss of spastic motions. The strength in both her arms returned, and she spontaneously moved her arm on the side experiencing hemiplegia. After three months, our patient could stick out her tongue upon demand. Finally, the swallow reflexes of our patient started to return. However, tube feeding was continued, and our patient died after aspiration of vomit following a feeding.ConclusionThe success of treatment with autologous activated immune cells in this patient may have resulted from the production of neuroactive substances, such as neurotrophin-3 and brain-derived neurotrophic factor, by activated immune cells. The deterioration of our patient could be reversed, as demonstrated by the restoration of motor strength in her hemiplegic side. In addition, our patient was able to induce motor responses upon request. It seems reasonable to conclude that activated immune cells may improve the chronic vegetative state in some patients.
The foot posture index, ankle lunge test, Beighton scale and the lower limb assessment score in healthy children: a reliability study
Authors: Evans Angela M , Rome Keith , Peet Lauren 
Published: January 2012

AbstractBackgroundOutcome measures are important when evaluating treatments and physiological progress in paediatric populations. Reliable, relevant measures of foot posture are important for such assessments to be accurate over time. The aim of the study was to assess the intra‐ and inter‐rater reliability of common outcome measures for paediatric foot conditions.MethodsA repeated measures, same‐subject design assessed the intra‐ and inter‐rater reliability of measures of foot posture, joint hypermobility and ankle range: the Foot Posture Index (FPI‐6), the ankle lunge test, the Beighton scale and the lower limb assessment scale (LLAS), used by two examiners in 30 healthy children (aged 7 to 15 years). The Oxford Ankle Foot Questionnaire (OxAFQ‐C) was completed by participants and a parent, to assess the extent of foot and ankle problems.ResultsThe OxAFQ‐C demonstrated a mean (SD) score of 6 (6) in adults and 7(5) for children, showing good agreement between parents and children, and which indicates mid‐range (transient) disability. Intra‐rater reliability was good for the FPI‐6 (ICC = 0.93 ‐ 0.94), ankle lunge test (ICC = 0.85‐0.95), Beighton scale (ICC = 0.96‐0.98) and LLAS (ICC = 0.90‐0.98). Inter‐rater reliability was largely good for each of the: FPI‐6 (ICC = 0.79), ankle lunge test (ICC = 0.83), Beighton scale (ICC = 0.73) and LLAS (ICC = 0.78).ConclusionThe four measures investigated demonstrated adequate intra‐rater and inter‐rater reliability in this paediatric sample, which further justifies their use in clinical practice.
Foot health education for people with rheumatoid arthritis: the practitioner's perspective
Authors: Graham Andrea S , Hammond Alison , Williams Anita E 
Published: January 2012

AbstractBackgroundPatient education is considered to be a key role for podiatrists in the management of patients with rheumatoid arthritis (RA). Patient education has undoubtedly led to improved clinical outcomes, however no attempts have been made to optimise its content or delivery to maximise benefits within the context of the foot affected by rheumatoid arthritis. The aim of this study was to identify the nature and content of podiatrists’ foot health education for people with RA. Any potential barriers to its provision were also explored.MethodsA focus group was conducted. The audio dialogue was recorded digitally, transcribed verbatim and analysed using a structured, thematic approach. The full transcription was verified by the focus group as an accurate account of what was said. The thematic analysis framework was verified by members of the research team to ensure validity of the data.ResultsTwelve members (all female) of the north west Podiatry Clinical Effectiveness Group for Rheumatology participated. Six overarching themes emerged: (i) the essence of patient education; (ii) the content; (iii) patient‐centred approach to content and timing; (iv) barriers to provision; (v) the therapeutic relationship; and (vi) tools of the trade.ConclusionThe study identified aspects of patient education that this group of podiatrists consider most important in relation to its: content, timing, delivery and barriers to its provision. General disease and foot health information in relation to RA together with a potential prognosis for foot health, the role of the podiatrist in management of foot health, and appropriate self‐management strategies were considered to be key aspects of content, delivered according to the needs of the individual. Barriers to foot health education provision, including financial constraints and difficulties in establishing effective therapeutic relationships, were viewed as factors that strongly influenced foot health education provision. These data will contribute to the development of a patient‐centred, negotiated approach to the provision of foot health education for people with RA.
Safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin α: results of a phase I randomized, placebo-controlled trial
Authors: Emu Brinda , Luca Diana , Offutt Carolyn , Grogan Jane L , Rojkovich Bernadette , Williams Marna B , Tang Meina T , Xiao Jim , Lee June H , Davis John C 
Published: January 2012

Abstract

Introduction

Pateclizumab (MLTA3698A) is a humanized mAb against lymphotoxin α (LTα), a transiently expressed cytokine on activated B and T cells (Th1, Th17), which are implicated in rheumatoid arthritis (RA) pathogenesis. This study was conducted to assess the safety, tolerability, < NOTE: For clarity and per AMA/S-W Style, please restore the use of Oxford/serial commas (ie: David likes vanilla, strawberry, and chocolate ice cream) throughout. and biologic activity of single and multiple doses of intravenous (IV) or subcutaneous (SC) pateclizumab in RA patients.

Methods

The single ascending dose (SAD) phase in patients with stable RA consisted of six cohorts (4:1 active:placebo at 0.3 mg/kg IV, 1.0 mg/kg IV, 1.0 mg/kg SC, 3.0 mg/kg IV, 3.0 mg/kg SC, and 5.0 mg/kg IV; n = 5/cohort). In the multiple ascending dose (MAD) phase, patients with prespecified RA disease activity received three doses of pateclizumab or placebo (4:1) every 2 weeks (1.0 mg/kg SC, n = 10; 3.0 mg/kg SC, n = 20; or 5.0 mg/kg IV, n = 5). Safety and tolerability were assessed throughout, and clinical activity was determined after three doses (Week 6).

Results

We observed no serious adverse events (AEs) or dose-limiting toxicities, and the majority of AEs were mild to moderate. The pharmacokinetic profiles were linear, and clearance was independent of dose. Reductions in levels of serum CXCL13 were observed, supporting the biologic activity of pateclizumab on the LTα pathway. Patients receiving pateclizumab in the 3.0 mg/kg MAD group (3.0 mg/kg SC) demonstrated ACR20, ACR50, and ACR70 response rates at week 6 of 75%, 56% and 25%, respectively, compared with 57%, 29%, and 0% in the placebo group. The median Disease Activity Score in 28 joints, C-reactive protein, reduction was 28% for pateclizumab, versus 8.4% for placebo.

Conclusions

Pateclizumabwas generally well-tolerated in RA patients. Preliminary evidence of clinical activity was observed in active RA patients at the dose level targeted for clinical effect.
Balancing harms and benefits of service mammography screening programs: a cohort study
Authors: Puliti Donella , Miccinesi Guido , Zappa Marco , Manneschi Gianfranco , Crocetti Emanuele , Paci Eugenio 
Published: January 2012

Abstract
Introduction
The use of screening mammography is still under debate within the medical community. The aim of this study is to define a balance sheet of benefits (breast cancer mortality reduction) and harms (overdiagnosis) for mammography screening programs.

Methods
We compared breast cancer incidence and mortality in two cohorts of women, defined as 'attenders' or 'non-attenders' on the basis of the individual attitudes towards screening, who were invited to the first round of the Florentine screening program. The effects of screening exposure on breast cancer incidence and mortality were evaluated by fitting Poisson regression models adjusted for age at entry, marital status and deprivation index. We performed a sensitivity analysis excluding 34 women not responding to the invitation with a breast cancer diagnosis in the following six months.

Results
In total, we included 51,096 women aged 50 to 69 years invited at the first screening round (1991 to 1993) and followed-up for breast cancer incidence and mortality until 31 December 2007 and 31 December 2008, respectively The estimate of mortality reduction varies from 45% among 50 to 59 year-old women up to 51% among 60 to 69 year-old women. The estimate of overdiagnosis, according to the cumulative-incidence method, is an additional 10% of all breast cancer cases among 60 to 69 year-old women screened.

Conclusions
Comparing the breast cancer mortality and breast cancer incidence between attenders and non-attenders, we have determined that the overall cost to save one life corresponds to no more than one over-diagnosed tumor (from 0.6 to 1 depending on the selection criteria of the cohort), even if a residual self-selection bias cannot be excluded.
Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study
Authors: Nederend Joost , Duijm Lucien EM , Voogd Adri C , Groenewoud Johanna H , Jansen Frits H , Louwman Marieke WJ 
Published: January 2012

Abstract
Introduction
The aims of this study were to determine trends in the incidence of advanced breast cancer at screening mammography and the potential of screening to reduce it.

Methods
We included a consecutive series of 351,009 screening mammograms of 85,274 women aged 50-75 years, who underwent biennial screening at a Dutch breast screening region in the period 1997-2008. Two screening radiologists reviewed the screening mammograms of all advanced screen detected and advanced interval cancers and determined whether the advanced cancer (tumor > 20 mm and/or lymph node positive tumor) had been visible at a previous screen. Interval cancers were breast cancers diagnosed in women after a negative screening examination (defined as no recommendation for referral) and before any subsequent screen. Patient and tumor characteristics were compared between women with advanced cancer and women with non-advanced cancer, including ductal carcinoma in situ.

Results
A total of 1,771 screen detected cancers and 669 interval cancers were diagnosed in 2,440 women. Rates of advanced cancer remained stable over the 12-year period; the incidence of advanced screen-detected cancers fluctuated between 1.5 - 1.9 per 1,000 screened women (mean 1.6 per 1,000) and of advanced interval cancers between 0.8 - 1.6 per 1,000 screened women (mean 1.2 per 1,000). Of the 570 advanced screen-detected cancers, 106 (18.6%) were detected at initial screening; 265 (46.5%) cancers detected at subsequent screening had been radiologically occult at the previous screening mammogram, 88 (15.4%) had shown a minimal sign, and 111 (19.5%) had been missed. Corresponding figures for advanced interval cancers were 50.9% (216/424), 24.3% (103/424) and 25.1% (105/424), respectively. At multivariate analysis, women with a ≥ 30 months interval between the latest two screens had an increased risk of screen-detected advanced breast cancer (OR 1.63, 95%CI: 1.07-2.48) and hormone replacement therapy increased the risk of advanced disease among interval cancers (OR 3.04, 95%CI: 1.22-7.53).

Conclusion
We observed no decline in the risk of advanced breast cancer during 12 years of biennial screening mammography. The majority of these cancers could not have been prevented through earlier detection at screening.
How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography
Authors: de Matos Gustavo FJ , Stanzani Fabiana , Passos Rogerio H , Fontana Mauricio F , Albaladejo Renata , Caserta Raquel E , Santos Durval CB , Borges João Batista , Amato Marcelo BP , Barbas Carmen SV 
Published: January 2012

Abstract
Introduction
The benefits of higher positive end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) have been modest, but few studies have fully tested the "open-lung hypothesis". This hypothesis states that most of the collapsed lung tissue observed in ARDS can be reversed at an acceptable clinical cost, potentially resulting in better lung protection, but requiring more intensive maneuvers. The short-/middle-term efficacy of a maximum recruitment strategy (MRS) was recently described in a small physiological study. The present study extends those results, describing a case-series of non-selected patients with early, severe ARDS submitted to MRS and followed until hospital discharge or death.

Methods
MRS guided by thoracic computed tomography (CT) included two parts: a recruitment phase to calculate opening pressures (incremental steps under pressure-controlled ventilation up to maximum inspiratory pressures of 60 cmH2O, at constant driving-pressures of 15 cmH2O); and a PEEP titration phase (decremental PEEP steps from 25 to 10 cmH2O) used to estimate the minimum PEEP to keep lungs open. During all steps, we calculated the size of the non-aerated (-100 to +100 HU) compartment and the recruitability of the lungs (the percent mass of collapsed tissue re-aerated from baseline to maximum PEEP).

Results
A total of 51 severe ARDS patients, with a mean age of 50.7 years (84% primary ARDS) was studied. The opening plateau-pressure was 59.6 (± 5.9 cmH2O), and the mean PEEP titrated after MRS was 24.6 (± 2.9 cmH2O). Mean PaO2/FiO2 ratio increased from 125 (± 43) to 300 (± 103; P < 0.0001) after MRS and was sustained above 300 throughout seven days. Non-aerated parenchyma decreased significantly from 53.6% (interquartile range (IQR): 42.5 to 62.4) to 12.7% (IQR: 4.9 to 24.2) (P < 0.0001) after MRS. The potentially recruitable lung was estimated at 45% (IQR: 25 to 53). We did not observe major barotrauma or significant clinical complications associated with the maneuver.

Conclusions
MRS could efficiently reverse hypoxemia and most of the collapsed lung tissue during the course of ARDS, compatible with a high lung recruitability in non-selected patients with early, severe ARDS. This strategy should be tested in a prospective randomized clinical trial.
Three-year mortality among alcoholic patients after intensive care: a population-based cohort study
Authors: Christensen Steffen , Johansen Martin B , Pedersen Lars , Jensen Reinhold , Larsen Kim M , Larsson Anders , Tønnesen Else , Christiansen Christian F , Sørensen Henrik T 
Published: January 2012

Abstract
Introduction
Alcoholic patients comprise a large proportion of patients in intensive care units (ICUs). However, data are limited on the impact of alcoholism on mortality after intensive care.

Methods
We conducted a cohort study among 16,848 first-time ICU patients between 2001 and 2007 to examine 30-day and 3-year mortality among alcoholic patients. Alcoholic patients with and without complications of alcohol misuse (for example, alcoholic liver disease) were identified from previous hospital contacts for alcoholism-related conditions or redemption of a prescription for alcohol deterrents. Data on medication use, demographics, hospital diagnoses, and comorbidity were obtained from medical databases. We computed 30-day and 3-year mortality and mortality rate ratios (MRRs) by using Cox regression analysis, controlling for covariates.

Results
In total, 1,229 (7.3%) ICU patients were current alcoholics. Among alcoholic patients without complications of alcoholism (n = 785, 4.7% of the cohort), 30-day mortality was 15.9% compared with 19.7% among nonalcoholic patients. Compared with nonalcoholic patients, the adjusted 30-day MRR was 1.04 (95% confidence interval (CI), 0.87 to 1.25). Three-year mortality was 36.2% compared with 40.9% among nonalcoholic patients, corresponding to an adjusted 3-year MRR of 1.16 (95% CI, 1.03 to 1.31). For alcoholic patients with complications (n = 444, 2.6% of the cohort), 30-day mortality was 33.6%, and 3-year mortality was 64.5%, corresponding to adjusted MRRs, with nonalcoholics as the comparator, of 1.64 (95% CI, 1.38 to 1.95) and 1.67 (95% CI, 1.48 to 1.90), respectively.

Conclusions
Alcoholic ICU patients with chronic complications of alcoholism have substantially increased 30-day and 3-year mortality. In contrast, alcoholics without complications have no increased 30-day and only slightly increased 3- year mortality.