Mechanical dispersion is associated with poor outcome in heart failure with a severely depressed left ventricular function and bundle branch blocks

Objectives: Bundle branch blocks (BBB)-related mechanical dyssynchrony and dispersion may improve patient selection for device therapy, but their effect on the natural history of this patient population is unknown.

Methods: A total of 155 patients with LVEF?≤?35% and BBB, not treated with device therapy, were included. Mechanical dyssynchrony was defined as the presence of either septal flash or apical rocking. Contraction duration was assessed as time interval from the electrocardiographic R-(Q-)wave to peak longitudinal strain in each of 17 left ventricular segments. Mechanical dispersion was defined as either the standard deviation of all time intervals (dispersion_SD) or as the difference between the longest and shortest time intervals (dispersion_delta). Patients were followed for cardiac mortality during a median period of 33 months.

Results: Mechanical dyssynchrony was not associated with survival. More pronounced mechanical dispersion_delta was found in patients with dyssynchrony than in those without. In the multivariate regression analysis, patients’ functional class, diabetes mellitus and dispersion_delta were independently associated with mortality.

Conclusions: Mechanical dispersion, but not dyssynchrony, was independently associated with mortality and it may be useful for risk stratification of patients with heart failure (HF) and BBB.

• Key Messages

• Mechanical dispersion, measured by strain echocardiography, is associated with poor outcome in heart failure with a severely depressed left ventricular function and bundle branch blocks.

• Mechanical dispersion may be useful for risk stratification of patients with heart failure and bundle branch blocks.

     

GPs’ perspectives of the patient encounter – in the context of standardized cancer patient pathways

Objective: We aim to explore how GPs assign meanings and act upon patients’ symptoms in primary care encounters in the context of standardized cancer patient pathways (CPPs).Design, setting and subjects: Thirteen individual interviews were conducted with GPs, at primary healthcare centers (n = 4) in one county in northern Sweden. Interviews were analyzed using grounded theory method. The results were then linked to symbolic interactionism.Main outcome measures: GPs’ perspectives about assigning meanings to patients’ presented symptoms and perception about CPPs.Results: In the encounter, GPs engaged in two simultaneous interactions, one with patients’ symptoms – and the other with CPPs. The core category Disentangling patients’ care trajectory consists of three categories, interpreted as GPs’ strategies developed to assign meaning to symptoms. These strategies are carried out not in a straightforward manner but rather in a conflicting way, illuminating the complexity of GPs’ daily work.Conclusions: Interacting with patients is vital for assigning meaning to presented symptoms. However, nowadays GPs are not only required to interact with patients, they are also required to interact with CPPs. These standardized routines might create pressure and demands on GPs, especially for those experiencing a lack of information about CPPs. Beside of carrying out the challenging patient/person-centered dialogues and interpreting presented symptoms, GPs also need to link the interpreted symptoms to CPPs. Therefore, it is essential that GPs are given opportunities at their workplaces to continuously be informed and be supported in order to practice CPPs and thereby optimize trajectories for patients undergoing cancer diagnostics.

Key points

•  Current awareness:
•  • GPs deliberation about patients’ trajectories is a complex process, often dealing with vague symptoms. How CPPs influence this process within the encounter has not been studied.
•  Main statements:  • GPs in our study were involved in two simultaneous interactions, one with patients’ symptoms in the encounter – and the other with CPPs within the healthcare organization.
•  • Symbolic interactionism helped capture how GPs deliberated about conflicting and paradoxical aspects of the encounter, in terms of balancing two contradictory ways of action that GPs face when providing patient/person-centered care and linking to CPPs.
•  • Based on our results, primary care needs support from healthcare organizations to build capacity about CPPs and how to use them.

     

The effects of one-year simvastatin therapy on women’s bone mineral density

Only few studies have reported that bone fracture risk is decreased in hypercholesterolemic postmenopausal women treated with statin therapy. Because of a lack of longitudinal studies on the effect of statins on bones, the aim of our investigation was to estimate the simvastatin therapy effects on bone mineral density in hypercholesterolemic postmenopausal women. Our investigation was carried out on 53 postmenopausal women with hypercholesterolemia. The women included in the study were divided into two groups. Group 1 was comprised of women with two or more (n=32) atherosclerosis risk factors, whereas group 2 had women with less than two (n=21) of these risk factors. All the women included in the study were placed on a hypocholesterolemic diet and the women in group 1 were additionally treated with 20 mg of simvastatin daily. The parameters of lipid status, body mass index, and L2–L4 densitometry were determined at baseline and then after one year. The simvastatin-treated group showed significant improvement of lipid parameters and increased bone mineral density. Finally, changes in bone mineral density between the groups showed significant differences (p<0.05). Although our investigation was carried out on a small group, our results showed a positive effect of the simvastatin therapy on the bone mineral density of postmenopausal women.     

Atacicept in patients with rheumatoid arthritis: Results of a multicenter,phase ib,double‐blind,placebo‐controlled,dose‐escalating,single‐ and repeated‐dose study

Objective

Atacicept is a recombinant fusion protein that binds and neutralizes B lymphocyte stimulator and a proliferation‐inducing ligand. The purpose of this study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of atacicept treatment in patients with rheumatoid arthritis (RA) and to collect exploratory data on clinical outcomes.

Methods

In this multicenter, phase Ib, randomized, placebo‐controlled, dose‐escalating trial, 73 patients were enrolled into 6 escalating‐dose cohorts. Patients received atacicept or placebo as single doses (70, 210, or 630 mg) or as repeated doses given at 2‐week intervals (3 doses of 70 mg, 3 doses of 210 mg, or 7 doses of 420 mg), followed by 10 weeks of trial assessments, with a followup assessment at 3 months after the final dose.

Results

Atacicept was well tolerated, with few differences between treatment groups and no obvious safety concerns. The pharmacokinetics profile was nonlinear, but was consistent and predictable across all doses and regimens. Treatment‐related decreases in immunoglobulin (particularly IgM) and rheumatoid factor levels were evident, and a clear decrease in anti–citrullinated protein antibodies was observed in the cohort that received 7 doses of 420 mg. The B cell response was biphasic, with an initial transient increase (dominated by memory B cells) followed by a dose‐related decrease (dominated by mature B cells). Clinical assessments showed trends toward improvement with the 3‐month treatment. Little effect on the erythrocyte sedimentation rate or C‐reactive protein levels was seen.

Conclusion

Atacicept was well tolerated both systemically and locally. The results demonstrated that the biologic activity of atacicept was consistent with its mechanism of action.

     

Pluralistic task shifting for a more timely cancer diagnosis. A grounded theory study from a primary care perspective

ObjectiveTo explore how cancer could be diagnosed in a more timely way.DesignGrounded theory analysis of primary care physicians’ free text survey responses to: ‘How do you think the speed of diagnosis of cancer in primary care could be improved?’. Secondary analysis of primary care physician interviews, survey responses, literature.SettingPrimary care in 20 European Örenäs Research Group countries.SubjectsPrimary care physicians: 1352 survey respondents (2013-2016), 20 Spanish and 7 Swedish interviewees (2015–2019).Main outcome measuresConceptual explanation of how to improve timeliness of cancer diagnosis.ResultsPluralistic task shifting is a grounded theory of a composite strategy. It includes task sharing – among nurses, physicians, nurse assistants, secretaries, and patients – and changing tasks with cancer screening when appropriate or cancer fast-tracks to accelerate cancer case finding. A pluralistic dialogue culture of comprehensive collaboration and task redistribution is required for effective pluralistic task shifting. Pluralistic task shifting relies on cognitive task shifting, which includes learning more about slow analytic reasoning and fast automatic thinking initiated by pattern recognition; and digital task shifting, which by use of eHealth and telemedicine bridges time and place and improves power symmetry between patients, caregivers, and clinicians. Financial task shifting that involves cost tracking followed by reallocation of funds is necessary for the restructuring and retraining required for successful pluralistic task shifting. A timely diagnosis reduces expensive investigations and waiting times. Also, late-stage cancers are costlier to treat than early-stage cancers. Timing is central to cancer diagnosis: not too early to avoid overdiagnosis, and never too late.ConclusionsWe present pluralistic task shifting as a conceptual summary of strategies needed to optimise the timeliness of cancer diagnosis.

Key points

• Cancer diagnosis is under-researched in primary care, especially theoretically. Thus, inspired by classic grounded theory, we analysed and conceptualised the field:
• Pluralistic task shifting is a conceptual explanation of how the timeliness of cancer diagnosis could be improved, with data derived mostly from primary care physicians.
• This includes task sharing and changing tasks including screening and cancer fast-tracks to accelerate cancer case finding, and requires cognitive task shifting emphasising learning, and digital task shifting involving the use of eHealth and telemedicine.
• Financial task shifting with cost tracking and reallocation of funds is eventually necessary for successful pluralistic task shifting to happen.