Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.     

Implementation of selective prevention for cardiometabolic diseases; are Dutch general practices adequately prepared?

Objective: Current guidelines acknowledge the need for cardiometabolic disease (CMD) prevention and recommend five-yearly screening of a targeted population. In recent years programs for selective CMD-prevention have been developed, but implementation is challenging. The question arises if general practices are adequately prepared. Therefore, the aim of this study is to assess the organizational preparedness of Dutch general practices and the facilitators and barriers for performing CMD-prevention in practices currently implementing selective CMD-prevention.

Design: Observational study.

Setting: Dutch primary care.

Subjects: General practices.

Main outcome measures: Organizational characteristics.

Results: General practices implementing selective CMD-prevention are more often organized as a group practice (49% vs. 19%, p?=?.000) and are better organized regarding chronic disease management compared to reference practices. They are motivated for performing CMD-prevention and can be considered as ‘frontrunners’ of Dutch general practices with respect to their practice organization. The most important reported barriers are a limited availability of staff (59%) and inadequate funding (41%).

Conclusions: The organizational infrastructure of Dutch general practices is considered adequate for performing most steps of selective CMD-prevention. Implementation of prevention programs including easily accessible lifestyle interventions needs attention. All stakeholders involved share the responsibility to realize structural funding for programmed CMD-prevention. Aforementioned conditions should be taken into account with respect to future implementation of selective CMD-prevention.

• Key Points

• There is need for adequate CMD prevention. Little is known about the organization of selective CMD prevention in general practices.

• ??The organizational infrastructure of Dutch general practices is adequate for performing most steps of selective CMD prevention.

• ??Implementation of selective CMD prevention programs including easily accessible services for lifestyle support should be the focus of attention.

• ??Policy makers, health insurance companies and healthcare professionals share the responsibility to realize structural funding for selective CMD prevention.

     

The influence of co-morbidity on health-related quality of life in asthma and COPD patients

This study examines the association between somatic co-morbidity and both general and disease-specific health-related quality of life (HRQoL) in patients with asthma and chronic obstructive pulmonary disease (COPD). A cross-sectional analysis was done among 161 COPD patients and 395 asthma patients, aged 40-75 years, recruited from general practice. In the total study population, 47% had no, 32% had one, and 21% had two or more somatic co-morbid conditions, with no significant differences between asthma and COPD patients. Co-morbidity appeared to be associated with poor disease-specific HRQoL in asthma [odds ratio (OR) = 2.08 (1.37-3.18)] and with poor general HRQoL in asthma [OR = 2.96 (1.93-4.53)] and COPD [1.81 (0.91-3.60)] patients. Poorest HRQoL was found in patients with more than one co-morbid condition. Cardiac disease and hypertension were associated with poor disease-specific HRQoL in asthma. Of all co-morbid conditions, musculoskeletal disorders were most strongly associated with poor general HRQoL. Cardiac disease was found to be associated with general and disease-specific HRQoL in asthma but not in COPD. In studies on patients with asthma or COPD aged 40-75 years, co-morbidity should be treated as a determinant of HRQoL.     

Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector

Retroviral-mediated gene transfer is the most attractive modality for gene transfer into hematopoietic stem cells. However, transduction efficiency has been low using amphotropic Moloney murine leukemia virus (MoMLV) vectors. In this study, we investigated modifications of gene transfer using amphotropic MoMLV vectors in cell-free supernatant for their ability to increase the currently low transduction of both committed hematopoietic progenitors, granulocyte-macrophage colony- forming units (CFU-GMs), and their precursors, long-term culture- initiating cells (LTC-IC). First, based on the observation that bone marrow cells express more gibbon ape leukemia virus (GALV) receptor (Glvr-1) than amphotropic receptor (Ram-1), PG13/LN, which is a MoMLV vector pseudotyped with the GALV envelope, was compared with the analogous amphotropic envelope vector (PA317/LN). Second, progenitor cell transduction efficiency was compared between CD34 enriched and nonenriched progenitor populations. Third, the duration of transduction in vitro was extended to increase the proportion of progenitor cells that entered cell cycle and could thereby integrate vector cDNA. In 20 experiments, 1 x 10(6) marrow or peripheral blood mononuclear cells (PBMCs)/mL were exposed to identical titers of pseudotyped PG13/LN vector or PA317/LN vector in the presence of recombinant human interleukin-1 (IL-1), IL-3, IL-6, and stem cell factor (SCF; c-kit ligand) for 5 days. 50% of fresh vector supernatant was refed daily. Hematopoietic progenitor cells as measured by G418-resistant granulomonocytic colony (CFU-GM) formation were transduced more effectively with PG13/LN (19.35%) than with PA317/LN (11.5%, P = .012). In 11 further experiments, enrichment of CD34 antigen positive cells significantly improved gene transfer from 13.9% G418-resistant CFU-GM in nonenriched to 24.9% in CD34-enriched progenitor cells (P < .01). To analyze gene transfer after extended growth factor-supported long-term culture, 1 x 10(6) marrow cells/mL were cultured with IL-1, IL-3, IL-6, and SCF (50 ng/mL each) for 1, 2, and 3 weeks. Fifty percent of PG13/LN supernatant with growth factors was refed on 5 days per week. Five percent of marrow CFU-GM and 67% of LTC-IC were G418 resistant at 1 week (n = 4), 60% of CFU-GM and 100% of LTC-IC were resistant at 2 weeks (n = 2) and 74% of CFU-GM (n = 4) and 82% of LTC-IC (n = 2) were resistant at three weeks.(ABSTRACT TRUNCATED AT 400 WORDS)     

Patient participation in medication reviews is desirable but not evidence-based: a systematic literature review

Aim

The aim of this systematic literature review is to investigate which types of patient participation in medication reviews have been practiced and what is known about the effects of patient participation within the medication review process.

Methods

A systematic literature review was performed in multiple databases using an extensive selection and quality assessment procedure.

Results

In total, 37 articles were included and most were assessed with a weak or moderate quality. In all studies patient participation in medication reviews was limited to the level of information giving by the patient to the professional, mainly on actual drug use. Nine studies showed limited results of effects of patient participation on the identification of drug related problems.

Conclusions

The effects of patient participation are not frequently studied and poorly described in current literature. Nevertheless, involving patients can improve patients'' knowledge, satisfaction and the identification of drug related problems. Patient involvement is now limited to information sharing. The profit of higher levels of patient communication and shared decision making is until now, not supported by evidence of its effectiveness.     

Myelosuppressive conditioning improves autologous engraftment of genetically marked hematopoietic repopulating cells in dogs

We have studied the role of different conditioning regimens for engraftment of genetically marked hematopoietic repopulating cells in dogs. Peripheral blood (PB) and/or marrow cells collected after treatment with recombinant canine stem cell factor (rcSCF) or cyclophosphamide were transduced in a vector-containing long-term culture system. Three different vector-producing cell lines with similar viral titers were used. In two of them, the neo-containing LN vector was packaged either in the PA317 cell line with an amphotropic murine retrovirus envelope or the PG13 cell line with the gibbon ape leukemia virus (GALV) envelope. The MFG/GC vector produced in PA317 cells contained the human glucocerebrosidase gene. Nineteen dogs received either no conditioning (group A, n = 5), irradiation to both humeri with 1,000 cGy (group B, n = 5), a sublethal dose of cyclophosphamide 40 mg/kg (group C, n = 4), a sublethal dose of 200 or 300 cGy total body irradiation (TBI) (group D, n = 3), or an otherwise lethal dose of 920 cGy TBI (group E, n = 3) before intravenous (groups A, C, D, E) or intramedullary (group B) infusion of the transduced autologous hematopoietic cells. Transduction efficiency of hematopoietic cells at the time of infusion into the animals was similar among the different conditioning groups. Dogs were observed for at least 6 months. PB granulocytes were obtained at least every 3 weeks after transplant and analyzed by polymerase chain reaction for the presence of the transduced genes. The percentages of positive results in dogs more than 4 weeks after transplantation were 0% without conditioning, 5% with local irradiation, 18% with sublethal cyclophosphamide, 33% with sublethal TBI, and 17% with otherwise lethal TBI. Analyzing the influence of conditioning regimens by a generalized estimating equation (GEE) technique, which considered the use of different retrovirus vectors and the number of mononuclear cells infused as potential confounding variables, we found that engraftment of genetically marked repopulating cells was significantly improved (P < .001) in dogs receiving systemic conditioning with either otherwise lethal TBI, sublethal TBI, or sublethal cyclophosphamide compared to dogs with local irradiation only or no conditioning. Within the limitation of the experimental design, these data suggest that myeloablative or myelosuppressive conditioning improves engraftment of genetically marked hematopoietic repopulating cells.