Implications of process evaluation for clinical effectiveness and clinical practice in a trial on chronic shoulder complaints

OBJECTIVE: The intervention process was evaluated in a randomised clinical trial on the effectiveness of a behavioural Graded Exercise Therapy (GET) programme for patients with chronic shoulder complaints in primary care settings. This process evaluation was done for three reasons: first, to know whether the programme was performed as planned; second, to know whether or not this treatment is feasible in normal practice; third, to identify needs for improvement of the protocol to facilitate implication. METHODS: We evaluated the extent to which the programme is being applied according to protocol, patient adherence to the programme and the suitability of the programme according to patients and physiotherapists. Twenty participating physiotherapists and 87 patients allocated to GET were asked to evaluate the intervention process. Furthermore, a sample of 10 patients, taken from the total number of 87 patients allocated to GET, was invited to take part in a focus group interview at the end of the study. We evaluated the intervention process using a treatment registration form filled in by the physiotherapists during treatment, evaluation forms filled in independently by physiotherapists and patients 26 weeks after the start of the treatment period, and information gathered during the focus group interview at the end of the study. RESULTS: GET was applied according to protocol to an acceptable extent, and participating patients showed satisfactory adherence to the programme. CONCLUSIONS: Clinical effectiveness of GET in this trial is not influenced by flaws in the application of the programme or by lack of patient adherence. PRACTICE IMPLICATIONS: The programme could be improved in terms of the process of goal-setting, and the implementation of GET could be facilitated if the programme is embedded in a multidisciplinary approach in primary care.     

Reducing fear of falling and avoidance of activity in elderly persons: the development of a Dutch version of an American intervention

OBJECTIVE: The present study reports on the development of a Dutch version of an American intervention for community-residing older persons in The Netherlands. Adaptation of this cognitive behavioural group intervention, to reduce fear of falling and avoidance of activity in older persons, was required before evaluation in a different setting. METHODS: The process of adaptation consisted of defining the target population, translating the original intervention manual literally, consulting Dutch experts and a developer of the original intervention, selecting qualified facilitators and conducting a pilot study of the adapted manual. RESULTS: Adaptations were incorporated to improve the content, feasibility and didactic materials. The main adaptations were scheduling more time for some activities, changing session frequency from twice to once a week, adding a booster session after 6 months and adding more transparencies. CONCLUSION: A critical assessment of the appropriateness and feasibility of the original intervention provided important information to facilitate replication in the Dutch setting. Applying a systematic approach is recommended in the process of adapting an original intervention for use in a different setting. PRACTICE IMPLICATIONS: To facilitate replication, in general, more detailed information should be provided about interventions.     

Diastolic myofilament dysfunction in the failing human heart

In recent years, it has become evident that heart failure is not solely due to reduced contractile performance of the heart muscle as impaired relaxation is evident in almost all heart failure patients. In more than half of all heart failure patients, diastolic dysfunction is the major cardiac deficit. These heart failure patients have normal (or preserved) left ventricular ejection fraction, but impaired diastolic function evident from increased left ventricular end-diastolic pressure. Perturbations at the cellular level which cause impaired relaxation of the heart muscle involve changes in Ca²⁺-handling proteins, extracellular matrix components, and myofilament properties. The present review discusses the deficits in myofilament function observed in human heart failure and the most likely underlying causal protein changes. Moreover, the consequences of impaired myofilament function for in vivo diastolic dysfunction are discussed taking into account the reported changes in Ca²⁺ handling.     

Maintaining group memberships: social identity continuity predicts well-being after stroke

A survey study of patients recovering from stroke (N = 53) examined the extent to which belonging to multiple groups prior to stroke and the maintenance of those group memberships (as measured by the Exeter Identity Transitions Scales, EXITS) predicted well-being after stroke. Results of correlation analysis showed that life satisfaction was associated both with multiple group memberships prior to stroke and with the maintenance of group memberships. Path analysis indicated that belonging to multiple groups was associated with maintained well-being because there was a greater likelihood that some of those memberships would be preserved after stroke-related life transition. Furthermore, it was found that cognitive failures compromised well-being in part because they made it hard for individuals to maintain group memberships post-stroke. These findings highlight the importance of social identity continuity in facilitating well-being following stroke and, more broadly, show the theoretical contribution that a social identity approach to mental health can make in the context of neuropsychological rehabilitation.     

Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections

Background  

The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission.     

Depressive symptoms in peripheral arterial disease: a follow-up study on prevalence, stability, and risk factors

BACKGROUND: Depressive symptoms are associated with poor prognosis in coronary artery disease, but there is a paucity of research on these symptoms in peripheral arterial disease (PAD). We examined the clinical correlates and 18-month course of depressive symptoms in PAD patients. METHODS: 166 patients with symptomatic lower-extremity PAD (39% women; M age=64.9 +/- 10 years) completed the 10-item Center for Epidemiological Studies Depression scale. A score > or =4 indicates clinically relevant depressive symptoms. Depressive symptoms were re-assessed at 6, 12, and 18 months follow-up. Ankle-brachial index (ABI) and treadmill walking distance were used to assess PAD severity. RESULTS: At baseline, depressive symptoms (CES-D > or =4) were present in 16% of the patients. Depressed patients performed worse regarding pain free (p=0.003) and maximum (p=0.005) walking distance. After adjusting for age, sex, education, ABI, psychotropic medication use, cardiovascular risk factors, and comorbidity, depressive symptoms remained stable in initially depressed patients. Using mixed modelling, three subgroups were identified in the total sample. The majority of PAD patients did not have depressive symptoms (58%), but there were two groups who persistently experienced either subclinical (27%) or clinically manifest (15%) depressive symptoms. LIMITATIONS: Only baseline data of ABI and treadmill walking performance were available. CONCLUSIONS: Depressive symptomatology was present in a substantial number of PAD patients, tended to be stable, and was associated with reduced walking distance. These apparently evident results are overlooked thus far in this patient group and deserve further attention in research and clinical care.     

Migration of dendritic cell based cancer vaccines: in vivo veritas?

Ex vivo generated cancer vaccines based on dendritic cells (DCs) are currently applied in the clinic. The migration of DCs from the tissues to the lymph nodes is tightly controlled and involves many different mediators and their receptors. A recent study demonstrated that the rate of migration of antigen-bearing DCs in situ from the skin to the lymph node is 100-fold higher than previously estimated. The migration of ex vivo generated DCs is rather inefficient but can be improved by pre-conditioning of the vaccine injection site with inflammatory cytokines. An alternative approach that is currently being explored is to target tumor antigens directly to DCs in situ, thereby exploiting the intricate migratory capacity of DCs in vivo. Recent advances have been made in understanding DC migration in the context of DC-based vaccines.     

TGFB1 genetic polymorphisms and coronary heart disease risk: a meta-analysis

ABSTRACT: BACKGROUND: Genetic variations in TGFB1 gene have been studied in relation to coronary heart disease (CHD) risk, but the results were inconsistent. METHODS: We performed a systematic review of published studies on the potential role of TGFB1 genetic variation in CHD risk. Articles that reported for the association of TGFB1 genetic variants with CHD as primary outcome were searched via Medline and HuGE Navigator through July 2011. The reference lists from included articles were also reviewed. RESULTS: Data were available from 4 studies involving 1777 cases and 7172 controls for rs1800468, 7 studies involving 5935 cases and 10677 controls for rs1800469, 7 studies involving 6634 cases and 9620 controls for rs1982073, 5 studies involving 5452 cases and 9999 controls for rs1800471, and 4 studies involving 5143 cases and 4229 controls for rs1800472. The pooled odds ratios (ORs) for CHD among minor T allele carriers of rs1800469, minor C allele carriers of rs1982073, and minor C allele carriers of rs1800471 versus homozygous major allele carriers was 1.14 (95% confidence interval [CI]: 1.05-1.24), 1.18 (95% CI: 1.04-1.35), and 1.16 (95% CI: 1.02-1.32), respectively. No substantial heterogeneity for ORs was detected among the included Caucasian populations for all SNPs. However, for rs1800471, the statistical significance disappeared after adjusting for potential publication bias. No significant association was found between rs1800468 and rs1800472 variants and CHD risk. CONCLUSION: Two genetic variants (rs1800469 and rs1982073) in TGFbeta1 are associated with CHD risk, minor allele carriers having a 15% increased risk.