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Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept., SCOPUS: ar.j, info:eu-repo/semantics/published

Aim To determine the health facility‐based perinatal mortality rate, its causes and avoidable factors using the perinatal mortality surveillance and response guidelines. Design This was an action study conducted in one of the districts in Western Uganda from 1 January–31 December 2019. Methods A total of 20 perinatal death cases were recruited consecutively. Data were collected using a Ministry of Health Perinatal Death Surveillance and Response (PDSR) questionnaire containing questions on pregnancy, delivery and immediate postnatal care. We used descriptive statistics to describe key data elements. Results We found a health facility‐based perinatal mortality rate of 17.3 deaths per 1,000 live births. Birth asphyxia was the most common cause of perinatal deaths. Seven, three and ten mothers delayed seeking, reaching and receiving appropriate health care, respectively.

Lack of both awareness and application of evidence-based principles for obesity care for people with obesity (PwO) limit employers' role in supporting effective obesity management among employees with obesity (EwO). The aim of the ACTION (Awareness, Care, and Treatment In Obesity maNagement) study was to explore the current state of employer wellness programs related to obesity management, evaluate the impact of obesity in the workplace, assess attitudes regarding the role of employers in managing obesity, and identify challenges in implementing workplace wellness programs as perceived by employer representatives (ERs) and EwO. An online survey was conducted among ERs and adult PwO (BMI ≥30 by self-reported height and weight) using a cross-sectional, US-based stratified sample design. There were 153 ER respondents and 3008 adult PwO respondents; 1478 PwO were employed full-time, part-time, or were self-employed. ERs recognize the seriousness of obesity and its negative impact on work productivity; however, wellness programs tend to fall short of addressing specific needs of EwO, evidenced by low participation and success rates reported by EwO. This study highlights the need for programs that address the complexities of obesity and the specific needs of EwO, which currently are inadequately addressed according to EwO.

AbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was an observational study of patients with rheumatoid arthritis who initiated intravenous abatacept in clinical practice. We aimed to compare abatacept retention rates and clinical outcomes in patients from Germany versus other countries. Baseline characteristics, crude retention rates, and clinical outcomes were compared by treatment line in the German cohort at 2 years. In addition, biologic-naive patients were compared with biologic-naive patients pooled from other participating countries. In the German cohort, 677/680 (99.6%) patients enrolled were evaluable and 171/677 (25.3%) were biologic naive. At baseline, abatacept monotherapy was received by a similar proportion of biologic-naive and biologic-failure patients in the German cohort, but by a greater proportion of biologic-naive patients in German versus other countries cohort (27.5 vs. 12.9%). The overall crude abatacept retention rate at 2 years in the German cohort was 39.9%; retention rate did not differ significantly by treatment line, but among biologic-naive patients it was lower in Germany than in the other countries cohort (42.1 vs. 58.7%; log-rank test p

BACKGROUND AND PURPOSE A prior study found a link between post-stroke blood-brain barrier disruption and functional outcomes. The current study aimed to replicate this finding in a cohort of patients recruited in the context of a randomized clinical trial. METHODS The ACTION trial was a study of natalizumab in acute stroke patients. Patients with MRI-perfusion weighted imaging (PWI) were included in this post-hoc analysis. Blood-brain permeability images (BBPI) were calculated from the PWI source images. Mean BBPI values from the 24 h time point were compared with modified Rankin scores (mRS) at 5, 30, and 90-day assessments using linear regression. Good functional outcome (mRS< = 1) was compared with mean BBPI using logistic regression. RESULTS One hundred and nineteen patients were included in the analysis (median age = 74, 43% female). Higher mean BBPI was associated with worse mRS at 5 days (p = 0.002; r2 = 0.078) and 30 days (p = 0.036; r2 = 0.039) but did not reach statistical significance at 90 days (p = 0.30; r2 = 0.010). When removing high-value outliers, all outcome measures showed a stronger relationship with mean BBPI. Logistic regression found that with every 1% increase in mean BBPI measured 24 h after the stroke, the likelihood of achieving a good functional outcome at 90 days is decreased by half (OR = 0.53; CI = 0.30:0.95; p = 0.032). CONCLUSIONS With sufficient image quality, elevated BBPI measured in the days after an ischemic event is predictive of worse functional outcome and may serve as a biomarker for post-stroke inflammation.

BackgroundHeart diseases are increasingly identified as an important indirect cause of maternal mortality in several cities in Indonesia. The management of pregnancy with heart diseases requires a multidisciplinary approach, and interprofessional collaboration practice (IPCP) is critical to improving the quality of patient care. To enable the effective implementation of IPCP, integrated care pathways (ICPs) are needed to define the roles and responsibilities of the health professionals involved. This study aims to examine the obstacles and enabling factors of IPCP, to develop and use ICPs in the implementation of IPCP in health care services for pregnant women with heart diseases.MethodsA participatory action study consisting of four stages (diagnostic, planning, implementation, and evaluation) will take approximately 2 years after consensus of ICPs are made. The primary data collection process will employ consensus, observations, focus group discussions, and in-depth interviews throughout the four stages, while secondary data from referral documents and medical records will be collected mainly during the diagnostic and evaluation stages. The findings are being analysed and will then be used to develop an ICPs through consensus building at the planning stage to be applied in the implementation stage. Finally, the implementation outcome, including acceptability, adoption, appropriateness, and feasibility of IPCP, will be assessed in the evaluation stage. All qualitative data will be analysed thematically by two coders using NVIVO 12 software.DiscussionThis research aims to assess the needs of IPCP, develop and use the ICPs in the implementation of IPCP in health care services for pregnant women with heart diseases. Findings from this study will be used for health service planning and policy making to strengthen practice of IPCP during the referral process. As a result, pregnant women with heart disease will have better access to high-quality services at every health care facility to reduce maternal mortality.Trial registrationRetrospectively registered in the ISRCTN registry with study IDISRCTN82300061on Feb 6, 2019.

Purpose Patients’ readiness for advance care planning (ACP) is often considered a prerequisite for starting ACP conversations. Healthcare professionals’ uncertainty about patients’ readiness hampers the uptake of ACP in clinical practice. This study aims To determine how patients’ readiness is expressed and develops throughout an ACP conversation. Methods A qualitative sub-study into the ACTION ACP conversations collected as part of the international Phase III multicenter cluster-randomized clinical trial. A purposeful sample was taken of ACP conversations of patients with advanced lung or colorectal cancer who participated in the ACTION study between May 2015 and December 2018 (n = 15). A content analysis of the ACP conversations was conducted. Results All patients (n = 15) expressed both signs of not being ready and of being ready. Signs of being ready included anticipating possible future scenarios or demonstrating an understanding of one’s disease. Signs of not being ready included limiting one’s perspective to the here and now or indicating a preference not to talk about an ACP topic. Signs of not being ready occurred more often when future-oriented topics were discussed. Despite showing signs of not being ready, patients were able to continue the conversation when a new topic was introduced. Conclusion Healthcare professionals should be aware that patients do not have to be ready for all ACP topics to be able to participate in an ACP conversation. They should be sensitive to signs of not being ready and develop the ability to adapt the conversation accordingly.

Background The ACTION study identified barriers to initiating and maintaining weight loss in patients with obesity; however, joint-related issues (pain, mobility and bleeding) may affect perceptions of patients with haemophilia and obesity (PwHO). Aim To identify patient and caregiver insights on the unique challenges of PwHO. Methods Following IRB approval, adults who self-identified as PwHO, spouses/partners of adult PwHO, and caregivers of adolescent PwHO (aged 12-17 years) completed an online survey between December 2017 and April 2018. Results Respondents included 124 adult PwHO, 45 spouses/partners and 42 caregivers. By calculated BMI, most adults were overweight (43%) or had obesity (51%); this differed from self-reported weight category. PwHO goals were improving health conditions (60%), having more energy (54%), reducing risks of weight (46%), and losing any weight (44%). Issues related to joint health were secondary for PwHO but frequently reported by spouses/parents. Most perceived weight loss to be a high priority (66%) and their responsibility (64%) but required a complete lifestyle change (63%). Most anticipated that weight loss would reduce joint pain (62%), bleeding (58%) and factor use (52%) and increase mobility (62%). Weight discussions with healthcare providers (HCPs) were commonly reported (51%). HCP discussions targeted improving health conditions (46%), achieving any weight loss (44%), being more active (73%) and improving eating habits (72%). Most PwHO (65%) perceived obesity as a disease and believe that 10% weight loss would be extremely beneficial (78%). In the past 5 years, 80% discussed being overweight and 68% losing weight; a minority reported being successful (9%) or somewhat successful (38%) with weight loss. More realistic or specific (51%/47%) goals, resources (46%), referrals to weight-loss programmes (41%) or dietitians (38%), meals or recipes (54%/50%), local or national (42%/41%) programmes for PwHO and success stories of PwHO (40%) are needed or would be helpful. Conclusions PwHO, spouse/partners and caregivers exhibited awareness of general and haemophilia-specific consequences of excess body weight. Most have tried general approaches to improve eating and increase activity with little success and desire more education on weight management and more details on specific actionable recommendations distributed through existing haemophilia channels. These insights will better inform the creation of weight-loss programmes for this community.

OBJECTIVE: Even when medical treatments are limited, supporting patients' coping strategies could improve their quality of life. Greater understanding of patients' coping strategies, and influencing factors, can aid developing such support. We examined the prevalence of coping strategies and associated variables.METHODS: We used sociodemographic and baseline data from the ACTION trial, including measures of Denial, Acceptance, and Problem-focused coping (COPE; Brief COPE inventory), of patients with advanced cancer from six European countries. Clinicians provided clinical information. Linear mixed models with clustering at hospital level were used.RESULTS: Data from 675 patients with stage III/IV lung (342, 51%) or stage IV colorectal (333, 49%) cancer were used; mean age 66 (10 SD) years. Overall, patients scored low on Denial and high on Acceptance and Problem-focused coping. Older age was associated with higher scores on Denial than younger age (β = 0.05; CI[0.023; 0.074]), and patients from Italy (β = 1.57 CI[0.760; 2.388]) and Denmark (β = 1.82 CI[0.881; 2.750]) scored higher on Denial than patients in other countries.CONCLUSIONS: Patients with advanced cancer predominantly used Acceptance and Problem-focused coping, and Denial to a lesser extent. Since the studied coping strategies of patients with advanced cancer vary between subpopulations, we recommend taking these factors into account when developing tailored interventions to support patients' coping strategies.

International audience; Background: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.Methods: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290.Findings: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070).Interpretation: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI.Funding: ACTION Study Group and AstraZeneca.

Abatacept retention rates were evaluated in the French cohort in the prospective ACTION study (2010-2013), which included patients with moderate-to-severe rheumatoid arthritis managed in everyday clinical practice and started on intravenous abatacept therapy.Two-year abatacept retention rates were evaluated in 455 patients classified according to treatment line, body mass index (BMI), and status for rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA).After 2 years, the overall abatacept retention rate was 44%. The retention rate was non-significantly higher in the patients with vs. without a history of unresponsiveness to at least one biologic (48.1% vs. 41.8%, respectively). No significant retention rate differences were found across BMI categories (444 patients;25, 45.5%; ≥25 to30, 48.9%; and ≥30, 36.6%). Neither were any significant differences demonstrated according to RF and ACPA status (RF+ and ACPA+, 45.7%; RF+ or ACPA+, 43.8%; and FR- and ACPA-, 39.1%).The 44% 2-year retention rate in the French ACTION cohort supports the usefulness of abatacept therapy. In this study, retention was not associated with treatment line, BMI, or antibody status.

Summary Obesity is a chronic disease with a significant and growing impact on Canadians. The “Awareness, Care and Treatment In Obesity MaNagement” (ACTION) Study investigated perceptions, attitudes and perceived barriers to obesity management among Canadian people with obesity (PwO), healthcare providers (HCPs) and employers. In this study adult PwO (body mass index ≥30 kg/m2, based on self‐reported height/weight), HCPs (physicians and allied HCPs managing PwO) and employers (≥20 employees; offering health insurance), completed online surveys between 3 August and 11 October 2017 in a cross‐sectional design. Survey respondents (N = 2545) included 2000 PwO, 395 HCPs and 150 employers. Obesity was viewed as a “chronic medical condition” by most PwO (60%), HCPs (94%) and employers (71%) and deemed to have a large impact on overall health (74%, 78%, 81%, respectively). Many PwO (74%) believed weight management was their own responsibility. While PwO (55%) reportedly knew how to manage their weight, only 10% reported maintaining ≥10% weight reduction for >1 year. Despite low success rates, the most commonly reported effective long‐term weight loss methods tried and/or recommended were “improvements in eating habits” (PwO 38%; HCP 63%) and “being more active” (PwO 39%; HCP 54%). PwO and HCPs reported very different perceptions of the quality and content of their interaction during obesity management discussions. These findings highlight the communication gaps and misunderstanding between PwO, HCPs and employers. This underscores the importance of, and need for, evidence‐based management of obesity and a collaborative approach and understanding of the complex nature of this chronic disease.

Objective: Our aim was to explore how differing attitudes, expectations, and experiences among people with obesity (PwO) and healthcare providers (HCPs) might have an impact on effectively implementing current obesity treatment guidelines. Methods: Online surveys were conducted among 3,008 adult PwO (BMI≥30 by self-reported height and weight) and 606 HCPs. Results: PwO with weight loss ≥ 10% during the previous three years were more likely to have been diagnosed with obesity and to have discussed a weight loss plan with an HCP. However, only 21% believe HCPs have a responsibility to actively contribute to their obesity treatment. Further, HCPs tend not to effectively communicate the diagnosis of obesity, its nature as a serious and chronic disease, the full range of treatment options, and obesity’s implications for health and quality of life. Regarding treatment goals, HCPs more often focus on BMI reduction, while PwO’s goals focus on improved functioning, energy, and appearance. HCPs also tend to underestimate their patients’ motivation to address their obesity. Twenty-eight percent of HCPs ‘completely agreed’ that losing weight was a high priority for PwO, whereas more than half of PwO ‘completely agreed’ that losing weight was a high priority for them. When asked how their HCP could better support them, PwO most often expressed a desire for helpful resources, as well as assistance with specific and realistic goal-setting to improve health. Conclusions: HCPs can more effectively implement obesity treatment guidelines by more clearly and proactively communicating with PwO about their diagnosis, health implications of obesity, desired treatment goals, and the full range of treatment options. HCPs should understand that most PwO believe that managing their disease is solely their own responsibility. HCPs can also encourage more effective conversations by better appreciating their patients’ motivation and treatment goals.

Background There is limited evidence for the effectiveness of social media to promote healthy behaviour among Indigenous Australians, including to reduce smoking. Social media has significant potential to stimulate interpersonal influence to quit, however an important knowledge gap is how and what content people choose to share with friends and family. This paper explores the decision making processes of community members for sharing tobacco control content with family and friends on Facebook. Methods Community researchers were paid to choose and share at least one tobacco control post per week for a period of 6 months on their personal Facebook page. They documented reasons for their choices, which were coded and analysed to determine features of messages most likely to be shared, and salient considerations in the decision-making process. Results Posts which are child-focused, feature Indigenous content, and are perceived as practical, relevant and credible, with a direct and unambiguous message, were most likely to be shared. Posts which included disgusting imagery about health impacts, were focused on the environment, or were ambiguous or sarcastic were less likely to be shared. Decisions were also based on whether content was perceived to contain new information, to be helpful for their friends, and to be consistent with the participant’s online identity, as well as the perceived sensitivity of content. The potential impact on expensive mobile data for videos was also a factor. Conclusions When designing tobacco control messages to be shared on social media, health promoters should take into account how information will align with positive self-image and can contribute to social capital among the intended audience, and generate interpersonal engagement. Content should complement, rather than attempt to replicate, some message features that are effective on traditional broadcast media. This study shows the potential for health services to incorporate a strategy of using paid local social media ‘champions’ or ‘ambassadors’ to disseminate tobacco control messages on Facebook through community networks.

Background A key objective of this study was to examine obesity care attitudes and behaviors of people with obesity (PwO) and determine independent factors associated with a self-reported sustained weight loss success outcome. Methods An online survey was conducted in 2015 among 3008 U.S. adult PwO (BMI > 30 through self-reported height and weight). Multivariate logistic models explained variation in weight loss success, defined as ≥ 10% weight loss in previous 3 years and maintained for > 1 year. Results Controlling for weight changes over time, we found significant associations between self-reported weight history and weight loss success. PwO who had personal motivation to lose weight, were willing to talk to a diabetes educator about their weight, who had their weight loss attempts recognized by a healthcare provider, and were diagnosed with “obesity” or “overweight” were more likely to report having success losing weight. Conclusions This study does not determine causality, but suggests motivation and engagement with PwO may impact weight loss, and presents a basis for assessing the mechanism involved. Determining such mechanisms may identify important targets to improve obesity treatment outcomes. Trial registration This study is registered with ClinicalTrials.gov, number NCT03223493, https://clinicaltrials.gov/ct2/show/NCT03223493. Registered July 17, 2017 (retrospectively registered).

Personal exposure to pesticides has not been well characterized, especially among adolescents. We used silicone wristbands to assess pesticide exposure in 14 to 16 year old Latina girls (N = 97) living in the agricultural Salinas Valley, California, USA and enrolled in the COSECHA (CHAMACOS of Salinas Examining Chemicals in Homes and Agriculture) Study, a youth participatory action study in an agricultural region of California. We determined pesticide concentrations (ng/g/day) in silicone wristbands worn for one week using gas chromatography electron capture detection and employed gas chromatography mass spectrometry to determine the presence or absence of over 1500 chemicals. Predictors of pesticide detections and concentrations were identified using logistic regression, Wilcoxon rank sum tests, and Tobit regression models. The most frequently detected pesticides in wristbands were fipronil sulfide (87%), cypermethrin (56%), dichlorodiphenyldichloroethylene (DDE) (56%), dacthal (53%), and trans-permethrin (52%). Living within 100 m of active agricultural fields, having carpeting in the home, and having an exterminator treat the home in the past six months were associated with higher odds of detecting certain pesticides. Permethrin concentrations were lower for participants who cleaned their homes daily (GM: 1.9 vs. 6.8 ng/g/day, p = 0.01). In multivariable regression models, participants with doormats in the entryway of their home had lower concentrations (p

Although young women are presumed to have low cardiovascular disease (CVD) risk and mortality, the mortality benefits secondary to ischemic heart disease have plateaued among young women,50 years.Women, 18-49 years (n = 595) among all participants (n = 1,045) in the Columbia University Heart Health in Action Study, were assessed for CVD risk burden, that is, presence of hypertension, diabetes mellitus, current tobacco use, hyperlipidemia, physical inactivity, and/or obesity. Anthropometrics (height, weight, waist circumference, and body mass index [BMI]); demographics; socioeconomic status, CVD risk factors, body size perception; knowledge and awareness of CV disease; and attitudes toward lifestyle perception were determined.Most were Hispanic (64.0%); non-Hispanic white (20.0%); or non-Hispanic black (8.7%), age = 35.9 ± 8.0 years. BMI was categorized as obese (≥30 kg/mAmong these young women, the majority had CVD risks and the CVD risk burden is high among young women, particularly among the overweight and obese and physically inactive. Strategies to encourage healthy lifestyles and reduce CVD risk factors among this vulnerable at-risk population are vital.

Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.

Background This study assessed the extent to which individuals with surgically operable cancer in Southeast Asia experience financially catastrophic out-of-pocket costs, discontinuation of treatment, or death. Methods The ACTION study is a prospective, 8-country, cohort study of adult patients recruited consecutively with an initial diagnosis of cancer from public and private hospitals. Participants were interviewed at baseline and 3 months. In this paper, we identified 4,584 participants in whom surgery was indicated in initial treatment plans and assessed the following competing outcomes: death, financial catastrophe (out-of-pocket costs of >30% of annual household income), treatment discontinuation, and hospitalization without financial catastrophe incurred. We then analyzed a range of predictors using a multinomial regression model. Results Of the participants, 72% were female and 44% had health insurance at baseline. At 3 months, 31% of participants incurred financial catastrophe, 8% had died, 23% had discontinued treatment, and 38% were hospitalized but avoided financial catastrophe. Health insurance status was found to be associated with lower odds of treatment discontinuation (odds ratio [OR], 0.60; 95% CI, 0.47-0.77) relative to hospitalization without financial catastrophe. Women had greater odds of financial catastrophe than men (OR, 1.35; 95% CI, 1.05-1.74), whereas lower socioeconomic status (range of indicators) was generally found to be associated with higher odds of death, treatment discontinuation, and financial catastrophe. Conclusion Priority should be given to measures such as programs to extend social health insurance to offset the out-of-pocket costs associated with surgery for cancer faced in particular by women, the uninsured, and individuals of low socioeconomic status in Southeast Asia.

The long-term safety, tolerability, and efficacy of high-dose 13.3 mg/24 h rivastigmine patch in severe Alzheimer disease was evaluated in a 24-week, open-label extension to the double-blind ACTION study. Safety and tolerability, and efficacy on the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV), Severe Impairment Battery (SIB), and ADCS-Clinical Global Impression of Change (ADCS-CGIC) were assessed. Overall, 197 patients continued on 13.3 mg/24 h patch; 199 uptitrated from 4.6 mg/24 h to 13.3 mg/24 h patch. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar in patients who continued on, and patients who uptitrated to, 13.3 mg/24 h patch (AEs: 57.9% and 59.8%; serious AEs: 16.2% and 16.1%; discontinuations: 11.2% and 12.1%, respectively). Larger mean changes from double-blind baseline were observed in patients uptitrated on the ADCS-ADL-SIV (-4.6; SD=8.7) and SIB (-7.0; SD=16.6), than those who continued on 13.3 mg/24 h patch (-3.9; SD=8.0 and -4.7; SD=16.8, respectively). ADCS-CGIC scores were comparable. There were no clinically relevant between-group differences in safety and tolerability. Greater decline was observed in patients with delayed uptitration to high-dose 13.3 mg/24 h patch than patients who continued on high-dose patch.

Summary Aims The 24-week, prospective, randomized, double-blind ACTION study investigated the efficacy, safety, and tolerability of 13.3 versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD). Methods Patients had probable AD and Mini–Mental State Examination scores ≥3–≤12. Primary outcome measures were as follows: Severe Impairment Battery (SIB) and AD Cooperative Study–Activities of Daily Living scale–Severe Impairment Version (ADCS-ADL-SIV). Secondary outcomes were as follows: ADCS-Clinical Global Impression of Change (ADCS-CGIC), 12-item Neuropsychiatric Inventory (NPI-12), and safety/tolerability. Results Of 1014 patients screened, 716 were randomized to 13.3 mg/24 h (N = 356) or 4.6 mg/24 h (N = 360) patch. Baseline characteristics/demographics were comparable. Completion rates were as follows: 64.3% (N = 229) with 13.3 mg/24 h and 65.0% (N = 234) with 4.6 mg/24 h patch. The 13.3 mg/24 h patch was significantly superior to 4.6 mg/24 h patch on cognition (SIB) and function (ADCS-ADL-SIV) at Week 16 (P

Background: Awareness of preferences regarding medical care should be a central component of the care of patients with advanced cancer. Open communication can facilitate this but can occur in an ad hoc or variable manner. Advance care planning (ACP) is a formalized process of communication between patients, relatives and professional caregivers about patients’ values and care preferences. It raises awareness of the need to anticipate possible future deterioration of health. ACP has the potential to improve current and future healthcare decision-making, provide patients with a sense of control, and improve their quality of life.Methods/Design: We will study the effects of the ACP program Respecting Choices on the quality of life of patients with advanced lung or colorectal cancer. In a phase III multicenter cluster randomised controlled trial, 22 hospitals in 6 countries will be randomised. In the intervention sites, patients will be offered interviews with a trained facilitator. In the control sites, patients will receive care as usual. In total, 1360 patients will be included. All participating patients will be asked to complete questionnaires at inclusion, and again after 2.5 and 4.5 months. If a patient dies within a year after inclusion, a relative will be asked to complete a questionnaire on end-of-life care. Use of medical care will be assessed by checking medical files. The primary endpoint is patients’ quality of life at 2.5 months post-inclusion. Secondary endpoints are the extent to which care as received is aligned with patients’ preferences, patients’ evaluation of decision-making processes, quality of end-of-life care and cost-effectiveness of the intervention. A complementary qualitative study will be carried out to explore the lived experience of engagement with the Respecting Choices program from the perspectives of patients, their Personal Representatives, healthcare providers and facilitators.Discussion: Transferring the concept of ACP from care of the elderly to patients with advanced cancer, who on average are younger and retain their mental capacity for a larger part of their disease trajectory, is an important next step in an era of increased focus on patient centered healthcare and shared decision-making.Trial registration: International Standard Randomised Controlled Trial Number: ISRCTN63110516 . Date of registration: 10/3/2014.

Objective To assess the impact of baseline body mass index (BMI) on the efficacy and retention of intravenous abatacept at 6 months in biologic-naive patients with rheumatoid arthritis (RA). Methods This was a 6-month analysis of a 2-year, non-interventional, international, prospective study. Baseline characteristics, clinical response and retention rates were compared by BMI subgroup: underweight/normal, overweight and obese ( 2 , respectively). Results BMI was reported in 643/672 (96%) patients: 264 (41%) were underweight/normal, 224 (35%) overweight and 155 (24%) obese. At baseline, the obese group had more active disease (mean [95% confidence intervals] 28-joint Disease Activity Score [C-reactive protein; derived] 4.6 [4.5, 4.7], 4.8 [4.7, 5.0] and 5.1 [4.9, 5.2] for underweight/normal, overweight and obese groups, respectively), a higher prevalence of metabolic disorders, a greater proportion of women and a lower proportion of patients with rheumatoid factor positivity. There were no significant differences in the percentages of patients achieving a good/moderate European League Against Rheumatism response by BMI group (80.7, 86.1 and 77.0% for underweight/normal, overweight and obese groups, respectively; P = 0.178). Overall retention rates at 6 months did not differ across groups (89, 92 and 89% for underweight/normal, overweight and obese groups, respectively; log-rank P = 0.382). After adjustment for baseline characteristics, BMI was not significantly associated with risk of discontinuation (reference BMI 2 ; hazard ratio [95% confidence intervals] 0.46 [0.22, 0.99] and 0.69 [0.34, 1.41] for overweight and obese patients, respectively). Conclusion BMI does not impact abatacept clinical response or retention in biologic-naive patients with RA.

Background— Galectin-3 is a soluble ß-galactoside–binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results— HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P Conclusions— Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00047437.

The ACTION (Assessment of Cost and ouTcomes of chemotherapy In an Observational setting) study investigated associations between chemotherapy, patient/disease characteristics and outcomes in advanced non-small cell lung cancer (NSCLC) patients in clinical practice.Chemonaïve NSCLC patients from five European countries were observed for 18 months from initiation of first-line chemotherapy; care was at the physician's discretion.Survival and associated prognostic factors were estimated using Kaplan-Meier methods and a Cox proportional hazards model, respectively. Cluster analyses of baseline patient characteristics were also performed. Toxicity data were not considered in these analyses.A total of 975 eligible patients with NSCLC (Stage IIIb/IV) were enrolled and provided baseline and response data; cluster analysis was performed on 829 patients and survival data were available from 906 patients. In first-line treatment, a 39.8% response rate, a 39.5% 1-year survival rate and unadjusted median survival of 9.3 months were observed. Prognostic factors for survival included performance status (PS), number of metastatic organs, gender and age. Five patient clusters were identified, highlighting patient heterogeneity in terms of baseline condition and age. PS was maintained or improved throughout first-line and second-line chemotherapy in half the patients receiving these treatments.ACTION provides valuable information about patient population, disease characteristics, treatment choices, prescribing patterns and outcomes in routine clinical practice in advanced NSCLC in Europe. Our findings suggest that maintenance of PS after first and subsequent lines of chemotherapy, and survival rates may both be higher than previously anticipated. Our results also showed an association between age and survival, which suggests that age should not exclude patients from receiving chemotherapy if they meet all other eligibility criteria.

More than three fourths of patients with heart failure (HF) are 65 years and older, and older age is associated with worse symptoms and prognoses than is younger age. Reduced exercise capacity is a chief HF complaint and indicates poorer prognosis, especially among elderly persons, but the mechanisms underlying functional decline in older patients with HF are largely unknown.Baseline cardiopulmonary exercise testing data from the HF-ACTION trial were assessed to clarify age effects on peak oxygen consumption (VO(2)) and ventilation-carbon dioxide production (VE/VCO(2)) slope.Among 2,331 New York Heart Association class II-IV patients with HF, increased age corresponded to decreased peak VO(2) (-0.14 mL kg(-1) min(-1) per year40 years; P.0001) and increased VE/VCO(2) slope (0.30 U/y70 years; P.0001). In a multivariable model with 34 other potential determinants, age was the strongest independent predictor of peak VO(2) (partial R(2) 0.130, total R(2) 0.392; P.001) and a significant but relatively weaker predictor of VE/VCO(2) slope (partial R(2) 0.037, total R(2) 0.199; P.001). Blunted peak heart rate was also a strong predictor of peak VO(2). Although peak heart rate and age were strongly correlated, both were significant independent predictors of peak VO(2) when analyzed simultaneously in a model. Aggregate comorbidity increased significantly with age but did not account for age effects on peak VO(2).Age is the strongest predictor of peak VO(2) and a significant predictor of VE/VCO(2) slope in the HF-ACTION population. Age-dependent comorbidities do not explain changes in peak VO(2). Age-related changes in cardiovascular physiology, potentially magnified by the HF disease state, should be considered a contributor to the pathophysiology and a target for more effective therapy in older patients with HF.

Objective: Despite the benefits of physical activity, people with arthritis are less active than the general population. The aim of this study was to determine the motivators and obstacles to physical activity for adults with arthritis. Methods: Participants were identified from the Obstacles to Action Study, a community based study of 8163 adults, which explored barriers and motivators to physical activity. A 1 : 1 case-control study was designed; cases were identified as those participants who reported arthritis (n = 1106). Each case was matched with an age, sex and ethnicity-matched non-arthritis control (n = 1106). Results: Cases were less likely to achieve recommended physical activity targets (58.8%vs. 68.1%P = 0.00001). Furthermore, fewer people with arthritis believed that physical activity would help them lead healthy lives (86.7%vs. 91.3%P = 0.006) or viewed physical activity as a priority (53.8%vs. 59.8%P = 0.005). Cases were less confident in their abilities to try a new activity (37.1%vs. 43.7%P = 0.002) or maintain a healthy weight (65.0%vs. 74.3%P = 0.00001). Cases also reported greater negative impact scores for barriers to activity, particularly arthritis, accessibility, cost and discomfort while exercising. Motivators and environmental barriers to activity were similar for cases and controls. These findings persisted after adjusting for educational level, body mass index and comorbidities. Conclusion: People with arthritis are less active and demonstrate different attitudes toward physical activity. Although people with arthritis identify similar environmental barriers, they have different psychosocial barriers. In order to design effective physical activity programs for people with arthritis, these barriers must be specifically addressed.

Background The emergence of new therapies for the treatment of rheumatoid arthritis (RA), the paucity of head-to-head studies, and the heterogeneous nature of responses to current biologics highlight the need for the identification of prognostic factors for treatment response and retention in clinical practice. Prognostic factors for patient retention have not been explored thoroughly despite data for abatacept and other biologics being available from national registries. Real-world data from the ACTION study may supplement the findings of randomized controlled trials and show how abatacept is used in clinical practice. The aim of this interim analysis was to identify prognostic factors for abatacept retention in patients with RA who received at least one prior biologic agent. Methods A large, international, non-interventional cohort of patients with moderate-to-severe RA who initiated intravenous abatacept in Canada and Europe (May 2008–January 2011) enrolled in the ACTION study. Potential prognostic factors for retention in this interim analysis (data cut-off February 2012; including patients from Canada, Germany, Greece, and Italy) were baseline demographics and disease characteristics, medical history, and previous and concomitant medication. Clinically relevant variables with p ≤ 0.20 in univariate analysis and no collinearity were entered into a Cox proportional hazards regression model, adjusted for clustered data. Variables with p ≤ 0.10 were retained in the final model (backward selection). Results The multivariate model included 834 patients. Anti-cyclic citrullinated peptide (CCP) antibody positivity (hazard ratio [95 % confidence interval]: 0.55 [0.40, 0.75], p

Background One of the biggest obstacles to developing policies in cancer care in Southeast Asia is lack of reliable data on disease burden and economic consequences. In 2012, we instigated a study of new cancer patients in the Association of Southeast Asian Nations (ASEAN) region – the Asean CosTs In ONcology (ACTION) study – to assess the economic impact of cancer. Methods The ACTION study is a prospective longitudinal study of 9,513 consecutively recruited adult patients with an initial diagnosis of cancer. Twelve months after diagnosis, we recorded death and household financial catastrophe (out-of-pocket medical costs exceeding 30 % of annual household income). We assessed the effect on these two outcomes of a range of socio-demographic, clinical, and economic predictors using a multinomial regression model. Results The mean age of participants was 52 years; 64 % were women. A year after diagnosis, 29 % had died, 48 % experienced financial catastrophe, and just 23 % were alive with no financial catastrophe. The risk of dying from cancer and facing catastrophic payments was associated with clinical variables, such as a more advanced disease stage at diagnosis, and socioeconomic status pre-diagnosis. Participants in the low income category within each country had significantly higher odds of financial catastrophe (odds ratio, 5.86; 95 % confidence interval, 4.76–7.23) and death (5.52; 4.34–7.02) than participants with high income. Those without insurance were also more likely to experience financial catastrophe (1.27; 1.05–1.52) and die (1.51; 1.21–1.88) than participants with insurance. Conclusions A cancer diagnosis in Southeast Asia is potentially disastrous, with over 75 % of patients experiencing death or financial catastrophe within one year. This study adds compelling evidence to the argument for policies that improve access to care and provide adequate financial protection from the costs of illness. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0433-1) contains supplementary material, which is available to authorized users.

This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)—AVINZA® (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin® (O-ER), oxycodone modified-release tablets given twice a day—in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the AMQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose.

OBJECTIVE Mixing rapid acting insulin analogs with detemir insulin to minimize daily injections has been adopted as a common regimen, especially for some children with type 1 diabetes, despite the manufacturing company’s caution against mixing these analogs in the same syringe. The effect of this practice on the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied. This crossover, randomized study was undertaken to determine whether mixing aspart with detemir insulin has an adverse effect on the early glucodynamic action of rapid-acting insulin analog in humans. RESEARCH DESIGN AND METHODS Eight adolescents with type 1 diabetes (age 17.3 ± 0.6 years and A1C 7.3 ± 0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4 units/kg detemir insulin were injected either as a separate or single mixed injection in random order. RESULTS Mixing the two insulins diminished the peak and overall early aspart insulin action with significantly lower maximum glucose infusion rate (GIRmax separate 6.1 ± 0.7 mg/kg/min vs. mix 4.5 ± 0.5 mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h of the insulin action study (separate 757 ± 105 mg/kg vs. mix 491 ± 66 mg/kg; P = 0.04). CONCLUSIONS These data demonstrate that mixing aspart with detemir insulin markedly lowers the early PD action of aspart and prolongs its time-action profile as compared with the separate injection of these analogs. These changes in insulin PD should be weighed against the added convenience of mixing when considering such unlicensed use of these insulins in youth with type 1 diabetes.

Background The use of assisted conception (AC) has been associated with higher risk of adverse perinatal outcome. Few data are available on the outcome of AC-neonates when pregnancy ends before 32 weeks of gestational age. The aim of this study was to compare the short-term outcome of AC- and naturally conceived preterm infants

Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial.This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6-18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00827411.Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15-18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio [HR] 1·17 [95% CI 0·68-2·03]; p=0·58). STEEPLE major bleeding events occurred more often in the continuation group (seven [1%] patients) compared with the interruption group (one [0·5%] patient; HR 0·15 [0·02-1·20]; p=0·073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 [2%] patients vs three [1%] patients; HR 0·26 [0·07-0·91]; p=0·04).Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment.Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.

Background: ACTION, a 24-week, prospective, randomized, parallel-group, double-blind study in patients with severe Alzheimer’s disease (AD), demonstrated significant efficacy of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch on the Severe Impairment Battery (SIB) and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale–Severe Impairment Version (ADCS-ADL-SIV). Overall, 61% of the study population received at least 1 dose of concomitant memantine, regardless of dose or duration. This retrospective analysis investigated the effects of concomitant memantine on the efficacy, safety and tolerability of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch. Methods: Patients were stratified according to whether or not they received at least one dose of concomitant memantine during the double-blind phase. Changes from baseline on the SIB and ADCS-ADL-SIV were compared using analysis of covariance (ANCOVA) with treatment, pooled center, memantine usage and treatment-by-memantine as factors, and baseline as a covariate. Safety and tolerability were assessed. Results: Memantine-treated patients were younger than those not receiving memantine (mean 75.9 and 78.8 years, respectively), with a lower screening Mini-Mental State Examination (8.6 and 9.2, respectively). ANCOVA confirmed there was no significant interaction (p>0.1) between study treatment and memantine use on the SIB or ADCS-ADL-SIV. The incidence of adverse events was: 71.4%, 13.3 mg/24 h patch with memantine; 79.7%, 13.3 mg/24 h patch alone; 74.7%, 4.6 mg/24 h patch with memantine; and 71.1%, 4.6 mg/24 h patch alone. Conclusion: These data suggest benefit of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch, regardless of concomitant memantine use. The incidence of adverse events with highdose patch was similar in memantine-treated patients and those not receiving memantine.

Background Discontinuation of rheumatoid arthritis (RA) treatment for lack or loss of initial response, tolerability issues, or development of antibodies against the therapeutic agent remains a challenge in clinical practice. Here we present a 6-month interim analysis of a 2-year prospective observational trial in Europe and Canada aiming to assess the real-world effectiveness, safety, and tolerability of intravenous abatacept for the treatment of moderate-to-severe RA. Methods ACTION (AbataCepT In rOutiNe clinical practice) is a prospective, observational study assessing effectiveness, safety, and tolerability of abatacept in patients with RA enrolled in Europe and Canada between May 2008 and January 2011. The patient population was divided into two groups: biologic naïve (‘first-line’) patients and patients who had previously failed treatment with at least one biologic agent (‘second-line’). Retention rates were calculated using Kaplan–Meier curve estimates. Effectiveness was measured using European League Against Rheumatism (EULAR) response criteria, the 28-item Disease Activity Score, the Clinical Disease Activity Index (CDAI), and physical function, as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Serious adverse events (SAEs) were reported for all enrolled patients. Results Of 1138 consecutively enrolled patients, 1114 and 1079 patients were evaluable for retention and effectiveness, respectively. Overall, retention rates were 88.6% (95% confidence interval [CI]: 86.4, 90.4); 67.4% of patients achieved good/moderate EULAR response; 32.8% had a CDAI Low Disease Activity State (LDAS); and 44.7% a HAQ-DI response. Retention rates among first- and second-line patients were 93.0% (95% CI: 85.9, 96.6) and 88.1% (95% CI: 85.7, 90.0), respectively. The percentage of patients achieving CDAI LDAS was 40.0% (95% CI: 26.4, 53.6) for first- and 32.2% (95% CI: 28.4, 36.0) for second-line patients and the proportion achieving a HAQ-DI response was 60.3% (95% CI: 47.8, 72.9) versus 43.1% (95% CI: 39.0, 47.2), respectively. The incidence of SAEs was 4.7%. Conclusions Evidence from this 6-month interim analysis suggests that abatacept offers an effective and well-tolerated treatment option for patients with RA, including those who have previously failed anti-tumor necrosis factor treatment. In addition, higher retention rates and effectiveness outcomes were observed when abatacept treatment was initiated earlier in the course of the disease.

Prophylaxis in severe haemophilia significantly increases health-related quality of life for patients, but the dosing frequency still constitutes a challenge. Thus, there is a need for new treatment options, utilizing compounds with longer duration of action, while still maintaining potency. The objective of this study was to evaluate the acute and prolonged effects of a new glycoPEGylated recombinant factor VIII (rFVIII) (N8-GP) in a venous bleeding model in haemophilia A mice and to compare the efficacy and potency to turoctocog alfa (rFVIII). Following intravenous administration of turoctocog alfa or N8-GP to normal and FVIII-deficient mice, bleeding time and blood loss from a saphenous vein incision were evaluated in an acute dose-response study and a duration of action study. In the acute setting, N8-GP dose dependently reduced the number and duration of bleeding episodes as well as blood loss compared to FVIII-deficient mice, reaching statistical significance at doses as low as 5-10 U kg(-1) . In the duration of action study, a significantly prolonged and maintained effect of N8-GP was found for up to 48 h after dosing, whereas the effect of rFVIII was no longer present for any end-points 24 h after dosing. Seventy-two hours after dosing, no significant effect of either compound was found. This study shows a prolonged haemostatic effect of N8-GP compared to rFVIII supporting other recent studies that N8-GP may hold a potential to increase the quality of life for patients with haemophilia A by reducing dosing frequency.

ObjectiveTo investigate characteristics of exposure to violence in relation to food security status among female-headed households.DesignOngoing mixed-method participatory action study. Questions addressed food insecurity, public assistance, and maternal and child health. Grounded theory analysis of qualitative themes related to violence was performed. These themes were then categorized by food security status.SettingHomes of low-income families in Philadelphia, PA, USA.SubjectsForty-four mothers of children under 3 years of age participating in public assistance programmes.ResultsForty women described exposure to violence ranging from fear of violence to personal experiences with rape. Exposure to violence affected mental health, ability to continue school and obtain work with living wages, and subsequently the ability to afford food. Exposure to violence during childhood and being a perpetrator of violence were both linked to very low food security status and depressive symptoms. Ten of seventeen (59 %) participants reporting very low food security described life-changing violence, compared with three of fifteen (20 %) participants reporting low food security and four of twelve (33 %) reporting food security. Examples of violent experiences among the very low food secure group included exposure to child abuse, neglect and rape that suggest exposure to violence is an important factor in the experience of very low food security.ConclusionsDescriptions of childhood trauma and life-changing violence are linked with severe food security. Policy makers and clinicians should incorporate violence prevention efforts when addressing hunger.

Objectives: In elderly individuals, little is known about changes in different anthropometric measures with respect to mortality. We examined the association between changes in eight anthropometric measures and mortality in an elderly population. Design: Longitudinal study including baseline measurements in 1988-1990 and repeated measures in 1993. Setting: European towns. Participants: A total of 1061 older adults born in 1913-1918 from the Survey in Europe on Nutrition and the Elderly, A Concerted Action study were included in this study. Measurements: Weight, body mass index, waist circumference, waist to hip ratio, waist to height ratio, mid-upper arm circumference (MUAC), triceps skinfold thickness, and corrected arm muscle area were taken during both measurements. Results: A Cox regression model was used to examine the association between anthropometric changes (divided into quintiles, smallest change - reference category) and all-cause and cardiovascular disease mortality over approximately 6 years of follow-up, adjusted for baseline measurement of application, age, sex, smoking, education, physical activity, and major chronic diseases. A decrease in weight (>= 3.2 kg), waist circumference (>= 3.1 cm), and MUAC (>= 1.6 cm and 0.6-1.6 cm) were (near) significantly associated with an all-cause mortality risk of 1.48 (95% CI: 0.99-2.20), 1.52 (95% CI: 1.01-2.31), 1.81 (95% CI: 1.17-2.79), and 1.66 (95% CI: 1.10-2.49), respectively. Also for MUAC, an increase (>= 1.3 cm) was significantly associated with an increased all-cause and cardiovascular disease mortality risk [hazard ratio, 1.52 (95% CI: 1.00-2.31) and 1.94 (95% CI: 1.00-3.75), respectively]. Conclusion: Associations were observed for decreases in only 3 of 8 anthropometric measures and all-cause mortality. Decreases in MUAC had the strongest association with mortality and was the only measure in which an increase also was associated with mortality. This suggests a role for MUAC in the prediction of mortality in elderly individuals. Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc.

Background: The ACTION trial was initiated to provide evidence from a randomised trial on the effects of chemotherapy in women aged over 70 years where evidence for risk and benefit are lacking. Methods: This was a randomised, phase III clinical trial for high risk, oestrogen receptor (ER) negative/ER weakly positive early breast cancer. The trial planned to recruit 1000 women aged 70 years and older, randomised to receive 4 cycles of anthracycline chemotherapy or observation. The primary endpoint was relapse-free interval. The trial included a pilot phase to assess the acceptability and feasibility of recruitment. Results: The trial opened at 43 UK centres. Information on number of patients approached was available from 38 centres. Of the 43 eligible patients that were approached, 39 were not randomised due to patients declining entry. After 10 months only 4 patients had been randomised and after discussion with the research funder, the trial was closed and funding terminated. Conclusion: Despite widespread support at several public meetings, input from patient groups including representation on the Trial Management Group, the trial failed to recruit due to the inability to convince patients to accept randomisation. It would therefore seem that randomising the patients to receive chemotherapy vs observation is not a viable design in the current era for this patient population.

Patients with stage 2 systolic hypertension require sizable blood pressure (BP) reductions to achieve recommended targets. This randomized double-blind study compared a single-pill combination of the direct renin inhibitor aliskiren and hydrochlorothiazide (aliskiren/HCTZ) with HCTZ monotherapy in older patients (older than 55 years) with systolic BP ≥160 mm Hg and

Two sizes of rivastigmine patch (5 cm(2) and 10 cm(2)) are currently approved in the US and Europe, while a 20 cm(2) rivastigmine patch has also been tested. A 15 cm(2) rivastigmine patch may provide an optimal balance between efficacy and safety. Earlier studies have demonstrated the efficacy of rivastigmine in severe Alzheimer's disease (AD), and supported the use of a higher dose patch in AD.The ACTION (ACTivities of daily living and cognitION) trial (Study CENA713DUS44) is designed to evaluate the efficacy and safety of low-dose versus high-dose rivastigmine transdermal patch in patients with severe AD.ACTION is a prospective, randomized, parallel-group, double-blind, multicenter study of patients (aged ≥50 years) with severe AD and a Mini-Mental State Examination score of 3-12. Novartis began recruitment in July 2009 and is conducting the trial in the United States. Patients are randomized to receive either a 5 cm(2) (4.5 mg/24 h) or a 15 cm(2) rivastigmine patch (13.3 mg/24 h) for 24 weeks. Patients receiving the 15 cm(2) patch will be up-titrated over 8 weeks, via 5 and 10 cm(2) patches. The primary efficacy outcomes include activities of daily living (ADLs), assessed with the Alzheimer's Disease Cooperative Study - Activities of Daily Living - Severe Impairment Version (ADCS-ADL-SIV), and cognition, assessed with the Severe Impairment Battery (SIB). Secondary outcomes include behavior (Neuropsychiatric Inventory), global functioning (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change), response rates, and safety.The ACTION trial examines the efficacy and tolerability of a 15 cm(2) rivastigmine patch over a 24-week period in patients with severe AD. This is a novel trial in the development of rivastigmine, as it uses a design that does not include a placebo arm, is recruiting patients with severe AD, and includes an ADL measure as a co-primary efficacy variable. CLINICAL REGISTRATION NUMBER: CENA713D US44.

Introduction Patients with systolic heart failure often have concomitant left ventricular (LV) diastolic dysfunction. Although in animal models diastolic dysfunction is associated with worsening exercise capacity and prognosis, information regarding these relationships in patients with established systolic heart failure (HF) is sparse. Methods HF-ACTION was a large, multicenter National Institutes of Health–funded trial of exercise training in systolic HF (LV ejection fraction [LVEF] ≤35%) and included detailed Doppler-echocardiographic (echo) and cardiopulmonary exercise testing at baseline. We tested the hypothesis that echo measures of LV diastolic function predict key cardiopulmonary exercise outcomes, including aerobic exercise capacity (peak exercise oxygen consumption, VO 2 ), distance in the 6-minute walk test (6MWD), and ventilatory efficiency (VE/VCO 2 slope) in patients with systolic HF. Results Overall, 2,331 patients (28% women, median age 59 years, median LVEF 25%) were enrolled. There were significant bivariate correlations between echo diastolic function variables and peak VO 2 (inverse) and VE/VCO 2 slope (direct) that were strongest for ratio of early diastolic peak transmitral (MV) to myocardial tissue velocity (E/E'), peak MV early-to-late diastolic velocity ratio (E/A), and left atrial dimension (range of absolute r = 0.16-0.28). Both MV E/A and E/E' were more strongly related to all 3 exercise variables than was LVEF. The relationships of E/A and E/E' with 6MWD were weaker than with peak VO 2 or VE/VCO 2 slope. A multivariable model with peak VO 2 as the dependent variable, which included MV E/A and 9 demographic predictors including age, sex, race, body mass index, and New York Heart Association class, explained 40% of the variation in peak VO 2 , with MV E/A explaining 6% of the variation. Including LVEF in the model explained less than an additional 1% of the variance in peak VO 2 . In a multivariable model for VE/VCO 2 slope, MV E/A was the strongest independent echo predictor, explaining 10% of the variance. The relationship of LV diastolic function variables with 6MWD was weaker than with peak VO 2 or VE/VCO 2 slope. Conclusion In patients with systolic HF, LV early diastolic function is a modest independent predictor of aerobic exercise capacity and appears to be a better predictor than LVEF.

In an era of globalization, increasing numbers of nursing programs are initiating international learning experiences, yet empirical data is lacking regarding long term benefits and effects of international placements. This paper presents findings from a participatory action study designed in response to this gap. Objectives were to describe student learning in international experiences, and to facilitate strategies that supported integration of this learning into personal and professional domains upon return to Canada. Seventeen students and three faculty participated over twelve months following their international experiences. Initial responses to the international experience included reports of new ways of viewing the world - often characterized by heightened social consciousness - yet in the immediate and longer-term many struggled with how to translate and sustain this learning in home settings. Considerable effort and intentionality was required to sustain social consciousness over time. Based on these findings, a preliminary framework for international experiences is presented.

Despite decline in needle sharing in some countries, many injectors continue to share injection paraphernalia such as cookers and cotton. While individual and structural factors are associated with injection risk behavior, little attention has been given to the influence of social network members, such as norms, on injection paraphernalia sharing. The present study is a longitudinal analysis of the association between perceived norms and sharing syringes and non-syringe injection paraphernalia. Participants were enrolled in the STEP into Action study and reported injection drug use at both baseline and follow-up assessments (n = 398). Results showed that descriptive norms, or believing that peers practiced risky injection behaviors, predicted sharing both syringes and nonsyringe paraphernalia. However, there was no association between injunctive norms (i.e., perceived peer approval) and either syringe or non-syringe paraphernalia sharing. Changing norms may lead to sustained behavior change. Accessible, norms-based interventions are needed to discourage drug injectors from sharing injection paraphernalia.

The authors' purpose in this action study was to examine the effect of a 10-week intervention, using the Disconnected Values Model (DVM), on changes in selected measures of fitness, blood lipids, and exercise adherence among 51 university faculty (10 men and 41 women) from a school in the southeastern United States. The DVM is an intervention model that is intended to provide incentive to replace unhealthy with healthy behavioral patterns. Multivariate Mixed Model analyses indicated significantly improved fitness (ie, cardiovascular, strength, percent body fat) and lipid profile (eg, blood cholesterol, triglycerides) scores between pre- and postintervention on all measures (ps.05) with the exception of blood pressure and high-density lipoprotein cholesterol (ps.05). Adherence for cardiovascular activity averaged 22 out of 30 sessions (73%), and strength-training adherence averaged 13 out of 20 sessions (65%). The results of this outcome-based study suggest that the DVM provides an effective cognitive-behavioral approach to promoting regular exercise.

AIM Efficacy and safety of biphasic insulin aspart (BIAsp 30, 30% short-acting and 70% intermediate-acting insulin aspart) added to an optimized treatment of metformin and pioglitazone (met/pio) were compared with treatment with optimized met/pio in type 2 diabetes patients. METHODS This randomized, 34-week, parallel-group study enrolled insulin-naive, type 2 diabetes patients (HbA(1c) 7.5-12.0%) previously using two oral antidiabetic (OAD) agents. During an 8-week run-in period, treatment was changed to met/pio and doses were adjusted up to 2500 mg/day and 30 or 45 mg/day respectively. Subjects either continued met/pio alone or added BIAsp 30 initiated at 6 units twice daily and titrated to target plasma glucose (PG) (4.4-6.1 mmol/l). RESULTS At end-of-study, subjects treated with BIAsp 30+met/pio (n = 93) had a mean (+/-s.d.) HbA(1c) reduction significantly greater than treatment with met/pio (n = 88) (1.5% +/- 1.1 vs. 0.2% +/- 0.9, p < 0.0001 between groups). Subjects treated with BIAsp 30+met/pio were more likely to reach The American Association of Clinical Endocrinologists and European Association for the Study of Diabetes/American Diabetes Association HbA(1c) targets of < or =6.5 and

textabstractAims: To evaluate the relationship between echocardiographic cardiac function and outcome in patients with stable symptomatic angina. Methods: Baseline echo left ventricular ejection fraction and volume data measured in a central laboratory was available for 7016 patients (92% of the total) participating in the ACTION trial (A Coronary disease Trial Investigating Outcome with Nifedipine GITS). Ejection fraction was also measured by investigators. Evaluation of the different echocardiographic variables was based on adjusted hazard ratios comparing the unfavourable limit of the 90% range of the variable concerned to the favourable limit. Results: The centrally measured ejection fraction was the most powerful predictor of all-cause death (adjusted hazard ratio = 2.5), myocardial infarction, any stroke or transient ischaemic attack and overt heart failure (adjusted hazard ratio = 4.5). The addition of either end systolic volume or end diastolic volume to ejection fraction did not materially affect the power of prediction. Compared to the central ejection fraction measurement, the investigator-measured ejection fraction was a less powerful predictor for all outcomes considered. Conclusion: Routine echocardiography carefully analysed by standardised methods provides useful prognostic information in patients with stable angina, including for total mortality.

Udgivelsesdato: 2003-Oct Alport syndrome (AS) is a type IV collagen hereditary disease characterized by progressive hematuric nephritis, hearing loss, and ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease characterized by much less severe disease in girls and women. A "European Community Alport Syndrome Concerted Action" (ECASCA) group was established to delineate the Alport syndrome phenotype in each gender and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of heterozygous girls and women belonging to the 195 families with proven COL4A5 mutation are compared with those of hemizygous boys and men. Hematuria was observed in 95% of carriers and consistently absent in the others. Proteinuria, hearing loss, and ocular defects developed in 75%, 28%, and 15%, respectively. The probability of developing end-stage renal disease or deafness before the age of 40 yr was 12% and 10%, respectively, in girls and women versus 90 and 80%, respectively, in boys and men. The risk of progression to end-stage renal disease appears to increase after the age of 60 yr in women. Because of the absence of genotype-phenotype correlation and the large intrafamilial phenotypic heterogeneity, early prognosis of the disease in X-linked Alport syndrome carriers remains moot. Risk factors for developing renal failure have been identified: the occurrence and progressive increase in proteinuria, and the development of a hearing defect.

The purpose of this action study was to apply an ecological program for teaching motor skills to individuals with disabilities in naturalistic settings. The program was developed based on an ecological survey. Participants were 22 individuals with disabilities, ages 7 to 26 years in the Fall of 1998 and 18 individuals with disabilities, ages 7 to 24 in the Winter of 1999. In each semester, a participant received one or two 50-min. training session(s) per week for 10 weeks. The number of steps in a motor-activity task performed correctly by a participant was measured in the first and last sessions in each semester. The magnitude of increase in the motor performance by participants and answers to questions in a short survey by participants' parents were used to describe the group performance. Analysis showed group performance of targeted motor skills could be improved using this ecological program in this local learning lab for special physical education.