Towards inclusive learning environments in post-graduate medical education: stakeholder-driven strategies in Dutch GP-specialty training.

BACKGROUND: A recent study found that ethnic minority General Practice (GP)-trainees receive more negative assessments than their majority peers. Previous qualitative research suggested that learning climate-related factors play a pivotal role in unequal opportunities for trainees in post-graduate medical settings, indicating that insufficient inclusivity had put minority students at risk of failure and dropout. STUDY OBJECTIVES: We aimed to develop broadly supported strategies for an inclusive learning climate in Dutch GP-specialty training. METHODS: We employed Participatory Action Research (PAR)-methods, incorporating Participatory Learning and Action (PLA)-techniques to ensure equal voices for all stakeholders in shaping Diversity, Equity, and Inclusion (DEI)-strategies for GP-specialty training. Our approach engaged stakeholders within two pilot GP-specialty training institutes across diverse roles, including management, support staff, in-faculty teachers, in-clinic supervisors, and trainees, representing ethnic minorities and the majority population. Purposeful convenience sampling formed stakeholder- and co-reader groups in two Dutch GP-specialty training institutes. Stakeholder discussion sessions were based on experiences and literature, including two relevant frameworks, and explored perspectives on the dynamics of potential ethnic minority trainees' disadvantages and opportunities for inclusive strategies. A co-reader group commented on discussion outcomes. Consequently, a management group prioritized suggested strategies based on expected feasibility and compatibility. RESULTS: Input from twelve stakeholder group sessions and thirteen co-readers led to implementation guidance for seven inclusive learning environment strategies, of which the management group prioritized three: • Provide DEI-relevant training programs to all GP-specialty training stakeholders; • Appoint DEI ambassadors in all layers of GP-specialty training; • Give a significant voice to minority GP-trainees in their education. CONCLUSION: The study's participatory approach engaged representatives of all GP-specialty training stakeholders and identified seven inclusive learning climate strategies, of which three were prioritized for implementation in two training institutions.

Blended learning in CME: the perception of GP trainers.

INTRODUCTION: Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. METHODS: In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. RESULTS: The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. CONCLUSION: GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

Influenza antigen-sparing by immune stimulation with Gram-positive enhancer matrix (GEM) particles.

Gram-positive enhancer matrix (GEM) particles, produced from non-genetically modified Lactococcus lactis bacteria have an inherent immunostimulatory activity. It was investigated whether co-administration of GEM particles can reduce the amount of influenza subunit vaccine (HA) necessary to protect mice from viral infection. Decreasing HA amounts of 5, 1, 0.2 and 0.04µg admixed with GEM particles were tested in intramuscular immunizations. Combinations of GEM and seasonal HA (A/Wisconsin/67/2005 [H3N2]) induced significantly higher systemic and better Th1/Th2-type balanced immune responses than HA alone. Addition of GEM to 0.04µg HA resulted in similar HI titers as 1-5µg non-adjuvanted HA. To test the protective efficacy of the adjuvanted combination, mice were immunized with influenza subunit vaccine A/PR/8/34 (H1N1) and then challenged with live virus (A/PR/8/34). Mice immunized with 1µg HA+GEM showed undetectable virus titers in the lungs 5 days after challenge, whereas mice immunized with 1µg HA alone showed detectable levels of virus in the lungs. Interestingly, mice vaccinated with the 0.04µg HA+GEM vaccine demonstrated reduced lung virus titers and a reduction in weight that was similar as that in mice vaccinated with 1µg non-adjuvanted HA. These results indicate that the use of GEM as immunostimulant allows for a strong reduction in the antigen dose as compared to the benchmark vaccine by using GEM particles. Thus, addition of GEM can strongly potentiate immunogenicity of influenza subunit vaccine both quantitatively and qualitatively.

Gastro-intestinal delivery of influenza subunit vaccine formulation adjuvanted with Gram-positive enhancer matrix (GEM) particles.

In this study, a liquid formulation of influenza subunit vaccine admixed with Gram-positive enhancer matrix (GEM) particles as adjuvant was delivered to upper and lower parts of intestinal tract. The aim was to determine the most effective immunization site in the intestines. Mice were vaccinated with a liquid formulation of GEM and influenza subunit vaccine orally and rectally. The oral administration of the vaccine with GEM particles induced a better systemic and mucosal immune response than oral (vaccine only) and rectal (with and without adjuvant) immunizations. Rectal administration elicited high IgG1 responses but little IgG2a, indicating a Th2 dominated immune response. In contrast, the oral immunization with GEM particles elicited a balanced IgG1 and IgG2a response. In conclusion, our results demonstrate that GEM-adjuvanted influenza vaccine should be targeted to the upper part of the intestinal tract.

Structural equation modeling of health-related quality-of-life data illustrates the measurement and conceptual perspectives on response shift.

OBJECTIVE: To illustrate different perspectives on response shift with cancer patients' health-related quality-of-life (HRQL) data. In measurement perspective, the focus is on bias in the measurement of HRQL. In conceptual perspective, the focus is on bias in the explanation of HRQL. STUDY DESIGN AND SETTING: Data came from a consecutive series of 202 newly diagnosed cancer patients, heterogeneous to cancer site, all undergoing surgery. A HRQL questionnaire was administered before and after surgery. Using structural equation modeling, biases and response shifts in measurement and explanation of HRQL were investigated with respect to patient's cancer site, health status, sex, age, optimism, and social comparison. RESULTS: Six measurement biases were found, five of which were considered response shift. The "general health" (GH) scale appeared most susceptible to response shift. For example, GH scores were not fully determined by HRQL but also by optimism before surgery and female sex and downward social comparison after surgery. Additionally, two explanation biases were found, neither of which were considered response shift-before and after surgery the mental component of HRQL was not only affected by cancer site and health status but also by optimism and downward social comparison. CONCLUSION: Our approach enables the distinction and testing of biases and response shifts in the measurement and explanation of HRQL.

Strongly enhanced dissolution rate of fenofibrate solid dispersion tablets by incorporation of superdisintegrants.

In this study, it was shown that the incorporation of superdisintegrants in solid dispersion tablets containing a high drug load can strongly enhance the dissolution rate of the highly lipophilic drug fenofibrate. In addition, the dissolution rate was more increased when the superdisintegrant was incorporated in the drug containing solid dispersions than when it was physically mixed with the solid dispersions. The dissolution rate enhancement strongly depended on the type of superdisintegrants and increased in the order Polyplasdone XL-10

Unexpected differences in dissolution behavior of tablets prepared from solid dispersions with a surfactant physically mixed or incorporated.

In a previous study, it was shown that the incorporation of poorly soluble drugs (BCS class II) in sugar glasses could largely increase the drug's dissolution rate [van Drooge, D.J., Hinrichs, W.L.J., Frijlink, H.W., 2004 b. Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions. J. Control. Release 97, 441-452]. However, the application of this technology had little effect when high drug loads or fast dissolving sugars were applied due to uncontrolled crystallization of the drug in the near vicinity of the dissolving tablet. To solve this problem a surfactant, sodium lauryl sulphate (SLS), was incorporated in the sugar glass or physically mixed with it. Diazepam and fenofibrate were used as model drugs in this study. The dissolution behavior of tablets prepared from solid dispersions in which SLS was incorporated was strongly improved. Surprisingly, the dissolution rate of tablets prepared from physical mixtures of SLS and the solid dispersion was initially fast, but slowed down after about 10 min. The solid dispersions were characterized by DSC to explain this unexpected difference. These measurements revealed the existence of interaction of SLS with both the drug and the sugar in the solid dispersion when SLS was incorporated. It is hypothesized that due to this interaction, the dissolution of SLS was slowed down by which a high solubility of the drug in the near vicinity of the dissolving tablet is maintained during the whole dissolution process. Therefore, uncontrolled crystallization is effectively prevented.

The use of animal models to study bacterial translocation during acute pancreatitis.

Infection of pancreatic necrosis with intestinal flora is accepted to be a main predictor of outcome during severe acute pancreatitis. Bacterial translocation is the process whereby luminal bacteria migrate to extraintestinal sites. Animal models were proven indispensable in detecting three major aspects of bacterial translocation: small bowel bacterial overgrowth, mucosal barrier failure, and disturbed immune responses. Despite the progress made in the knowledge of bacterial translocation, the exact mechanism, origin and route of bacteria, and the optimal prophylactic and treatment strategies remain unclear. Methodological restrictions of animal models are likely to be the cause of this uncertainty. A literature review of animal models used to study bacterial translocation during acute pancreatitis demonstrates that many experimental techniques per se interfere with intestinal flora, mucosal barrier function, or immune response. Interference with these major aspects of bacterial translocation complicates interpretation of study results. This paper addresses these and other issues of animal models most frequently used to study bacterial translocation during acute pancreatitis.

The use of Stokes deformation number as a predictive tool for material exchange behaviour of granules in the 'equilibrium phase' in high shear granulation.

The objective of this study was three-fold; to investigate the different mechanisms of material exchange during the equilibrium phase of the granulation process and whether these mechanisms are consistent with the mechanisms described in the growth regime map, to study how material properties and process conditions affect these exchange mechanisms, and to correlate Stokes deformation number to the exchange mechanisms. Microcrystalline cellulose (MCC), alpha-lactose, microfine cellulose (MFC), and dextrin were granulated using water as a binding agent. Once in the equilibrium phase, 5% (w/w) of the granular mass was replaced with wet tracer granules, after which the granulation process was continued. Granules were typically of a size of approximately 1mm in diameter. Therefore, these granules can also be called pellets. Tracer experiments show indeed solid material exchange can take place in the equilibrium phase of the high shear granulation process. Tracer material was equally dispersed throughout the whole batch for all materials tested. However, the granulation time needed to reach this homogeneous distribution varied with material and granulation conditions. Three different mechanisms of material exchange were identified: exchange by disintegration, where granules are rapidly crushed and formed to granules again; exchange by deformation, where abraded granule fragments immediately fuse with other granules; and exchange by distribution, where there is a prolonged period over which both tracer and standard granules stay intact, followed by uncontrolled growth and exchange of material. It was found that it is possible to shift between the mechanisms by changing the process conditions, e.g., changing viscosity or amount of binder liquid. These observations indicate that by choosing the appropriate process conditions improved distribution of small amounts of insoluble materials in the granules can be obtained. A relation exists between the exchange mechanisms and the growth regime map: the disintegration mechanism resembles 'crumb behaviour', the deformation mechanism resembles 'steady growth', and the distribution mechanism resembles 'nucleation' and 'induction growth'. Unfortunately, Stokes deformation number cannot be used as a predictive tool when low viscosity binders like water are used, due to the importance of viscosity in the equation. However, this number is one of the variables of the growth regime map. Since the exchange mechanisms correspond to the granule growth mechanisms in the regime map, alternatively colour experiments might be used to reveal the granulation regime.

Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques.

The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass transition temperature (T(g)), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-diazepam solid dispersions prepared by fusion for all drug loads tested (10-80 wt.%). The T(g) of these solid dispersions gradually changed with composition and decreased from 177 degrees C for pure PVP to 46 degrees C for diazepam. These observations indicate that diazepam was dispersed in PVP on a molecular level. However, in PVP-diazepam solid dispersions prepared by freeze drying, two T(g)'s were observed for drug loads above 35 wt.% indicating phase separation. One T(g) indicated the presence of amorphous diazepam clusters, the other T(g) was attributed to a PVP-rich phase in which diazepam was dispersed on a molecular level. With both the value of the latter T(g) and the DeltaC(p) of the diazepam glass transition the concentrations of molecular dispersed diazepam could be calculated (27-35 wt.%). Both methods gave similar results. Water vapour sorption (DVS) experiments revealed that the PVP-matrix was hydrophobised by the incorporated diazepam. TMDSC and DVS results were used to estimate the size of diazepam clusters in freeze dried PVP-diazepam solid dispersions, which appeared to be in the nano-meter range. The inulin-diazepam solid dispersions prepared by spray freeze drying showed one T(g) for drug loads up to 35 wt.% indicating homogeneous distribution on a molecular level. However, this T(g) was independent of the drug load, which is unexpected because diazepam has a lower T(g) than inulin (46 and 155 degrees C, respectively). For higher drug loads, a T(g) of diazepam as well as a T(g) of the inulin-rich phase was observed, indicating the formation of amorphous diazepam clusters. From the DeltaC(p) of the diazepam glass transition the amount of molecularly dispersed diazepam was calculated (12-27 wt.%). In contrast to the PVP-diazepam solid dispersions, DVS-experiments revealed that inulin was not hydrophobised by diazepam. Consequently, the size of diazepam clusters could not be estimated. It was concluded that TMDSC enables characterization and quantification of the molecular distribution in amorphous solid dispersions. When the hygroscopicity of the carrier is reduced by the drug, DVS in combination with TMDSC can be used to estimate the size of amorphous drug clusters.

Solid dispersions based on inulin for the stabilisation and formulation of delta 9-tetrahydrocannabinol.

The aim of this study was to develop a dry powder formulation that stabilises the chemically labile lipophilic Delta(9)-tetrahydrocannabinol (THC), that rapidly dissolves in water in order to increase the bioavailability and that opens new routes of administration. It was investigated whether these aims can be achieved with solid dispersions consisting of a matrix of inulin, an oligo-fructose, in which THC is incorporated. These solid dispersions were prepared by lyophilisation of a solution of THC and inulin in a mixture of water and tertiary butyl alcohol (TBA). Both 4 and 8 wt.% of THC could be incorporated in a glassy matrix of inulin. In the solid dispersions only 0.4-0.5 wt.% of residual TBA was present after storage at 20 degrees C/45% relative humidity (RH) for 7 days. Unprotected THC was completely degraded after 40 days of exposure to 20 degrees C and 45% RH. However, solid dispersions exposed to the same conditions still contained about 80% non-degraded THC after 300 days. Dissolution experiments with tablets compressed from inulin glass dispersion material showed that THC and inulin dissolved at the same rate. Tablets weighing 125 mg and containing 2mg THC were prepared from a mixture of THC containing solid dispersion, polyvinylpolypyrrolidone (PVPP) and mannitol. Dissolution tests revealed that from these tablets 80% of the THC was dissolved within 3 min, which makes them promising for sublingual administration. It was concluded that THC can be strongly stabilized by incorporating it in a matrix of inulin. The aqueous dissolution rate was high which may improve bioavailability.

Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis.

The objective of this study is to investigate the effects of an acute necrotizing pancreatitis (ANP), without biliary obstruction, on the migrating motor complex (MMC), small bowel bacterial overgrowth (SBBO), bacterial translocation (BT) and infection of the pancreas simultaneously. Rats were divided into four groups: mild pancreatitis, control, ANP and sham operated control. Jejunal myoelectrodes were used to measure MMCs. Blood, peritoneal fluid, bile, and abdominal organs were harvested for microbial culturing 72 h after induction of pancreatitis. The splenic portion of the pancreas was taken for histology. During ANP the MMC cycle length was significantly increased from 14.1 +/- 0.2 to 22.4 +/- 1.9 min (P < 0.05). The duodenum of ANP rats was in contrast with the other groups characterized by Enterobacteriacae (> 3 log 10 CFU g-1 in seven of 12 rats, P < 0.05). A positive correlation (r = 0.78, P < 0.01) existed between duodenal Gram-negative and anaerobic flora and the MMC cycle. Correlation between MMC cycle length and BT to the pancreas was positive as well (r = 0.70, P < 0.01). A positive correlation (r = 0.85, P < 0.01) was found between the severity of pancreatitis and duodenal bacterial overgrowth. During ANP without biliary obstruction, the jejunal MMC is disturbed and consequently SBBO occurs. The correlation between the severity of pancreatitis, the disturbance of the MMC and SBBO suggests an important pathophysiological role of the proximal small bowel in the infection of pancreatic necrosis.

Pore formation in tablets compressed from binary mixtures as a result of deformation and relaxation of particles.

This paper describes the internal structure of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch. The minimum particle diameter of pregelatinised starch inside tablets compressed from mixtures was calculated from the difference between the initial pore size distribution and the pore size distribution after removal of the starch particles by burning. Subsequently, the tablets were carefully crushed. These powders, consisting of almost only sodium chloride particles, were measured by laser diffraction. It was found that the diameter of the sodium chloride particles hardly changed, whereas the minimum diameter of starch particles strongly decreased during the compaction process. As an effect of the difference in yield pressure, the harder sodium chloride particles cause deformation of the softer starch particles, resulting in a change in particle shape. The pore size distribution of tablets compressed from mixtures of sodium chloride and starch is typically that of viscoelastic materials; the larger pores (>5 microm) change, while the small pores stay constant in number and size. The median pore diameter in tablets compressed from the mixtures is higher than the median pore diameter in tablets compressed from the pure materials. This paper shows that the formation of large pores was the result of the extra porosity expansion of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch.

Multicentre evaluation of the VITEK 2 Advanced Expert System for interpretive reading of antimicrobial resistance tests.

Interpretive reading analyses the complete resistance profiles of bacteria to multiple antibiotics and infers the resistance mechanisms present; it aids therapeutic choice and enhances surveillance data. We evaluated the Advanced Expert System (AES), which interprets MICs generated by the VITEK 2. Ten European laboratories tested 42 reference strains and 76-106 of their own strains, representing important resistance genotypes. Interpretive reading by the VITEK 2 AES achieved full agreement with genotype data for 88-89% of strains, with the correct mechanism identified as one of two possibilities for a further 5-6%. Mechanisms inferred with 90% agreement with reference data included methicillin resistance in staphylococci, glycopeptide resistance in enterococci, quinolone resistance in staphylococci and Enterobacteriaceae, AAC(6')-APH(2")-mediated aminoglycoside resistance in Gram-positive cocci, erm-mediated macrolide resistance in pneumococci, extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae and Pseudomonas aeruginosa, and acquired penicillinases in Enterobacteriaceae. VanA, VanB and VanC phenotypes of enterococci were distinguished reliably, and ESBL production was accurately inferred in AmpC-inducible species as well as Escherichia coli and Klebsiella spp. Mechanisms identified, but only as possibilities among several, included IRT-type beta-lactamases and individual aminoglycoside-modifying enzymes in Enterobacteriaceae. Most disagreements with reference data concerned pneumococci found to have high-level penicillin resistance by the VITEK 2 AES but previously determined, phenotypically, to have intermediate resistance. When ESBL production was inferred in E. coli and klebsiellae, the VITEK 2 AES edited susceptible results for cephalosporins (except cefoxitin) to resistant; when an acquired penicillinase was inferred in Enterobacteriaceae, piperacillin results were edited to resistant; and when staphylococci were found methicillin resistant, resistance was reported for all beta-lactams. Further editing may be desirable (e.g. of cephalosporin results for salmonellas inferred to have ESBLs).

Multiple "slow" CT scans for incorporating lung tumor mobility in radiotherapy planning.

PURPOSE: The high local recurrence rates after radiotherapy in early-stage lung cancer may be due to geometric errors that arise when target volumes are generated using fast spiral CT scanners. A "slow" CT technique that generates more representative target volumes was evaluated. METHODS AND MATERIALS: Planning CT scans (slice thickness 3 mm, reconstruction index 2.5 mm) were performed during quiet respiration in 10 patients with peripheral lung lesions. Planning CT scans were repeated twice, followed by three slow CT scans (slice thickness 4 mm, index 3 mm, revolution time 4 s/slice). All, except the first scan, were limited to the tumor region. Three-dimensional registration of all scans was performed. The reproducibility of the imaged volumes was evaluated with each technique using (1) the common overlapping volume (COM), the component of the clinical target volume (CTV) covered by all three CT scans, and (2) the encompassing volume (SUM), which is the volume enveloped by all CTVs. RESULTS: In all patients, the target volumes generated using slow CT scans were larger than those derived using planning scans (mean ratio of planning-CTV:slow-CTV of 88.8% +/- 5.6%), and also more reproducible. The mean ratio of the respective COM:SUM volumes was 62.6% +/- 10.8% and 54.9% +/- 12.9%. CONCLUSIONS: Larger, and more reproducible, target volumes are generated for peripheral lung tumors with the use of slow CT scans, thereby indicating that slow scans can better capture tumor movement.

Dosimetric consequences of tumor mobility in radiotherapy of stage I non-small cell lung cancer--an analysis of data generated using 'slow' CT scans.

BACKGROUND: The target coverage for radiotherapy of early-stage lung cancer was evaluated using two different CT techniques. MATERIALS AND METHODS: A conventional planning CT scan and two limited scans of the tumor region were performed in seven patients with peripheral tumors. Three 'slow' scans (slice thickness 4mm, index 3mm, revolution time 4s/slice) were then performed, followed by three-dimensional image registration. Planning target volumes (PTV) were generated using these GTV-PTV margins: (a) 1cm (PTV1.0); (b) 1.5 cm (PTV1.5); and (c) 0.9, 1.0, and 0.9 cm ('PTV(clinical)') when set-up errors are avoided. RESULTS: PTVs derived from three 'slow' scans missed 1.9% of the volume derived from three planning scans for an immobile tumor and 9.3% in the case of a mobile tumor. For an immobile tumor, PTV1.5 achieved comparable coverage to that achieved using PTVclinical, which was generated from three 'slow' scans and a planning scan. For a mobile tumor, PTV(1.5) covered only 89% of the volume captured by PTVclinical. PTV1.0 resulted in inadequate target coverage in all the patients. Reductions in potential lung toxicity (V20) were achievable in six patients despite the larger GTVclinical when treatment set-up errors were minimized. CONCLUSIONS: PTVs derived using 'slow' CT scans consistently produce superior target coverage than that using conventional scans. This may account for the poor local control observed in stage I lung cancer.

[Reduced risk of complications associated with severe acute (necrotizing) pancreatitis by administration of antibiotics; results from a literature review]. / Kleinere kans op complicaties van ernstige acute (necrotiserende) pancreatitis door toediening van antibiotica; resultaten van een literatuuronderzoek.

OBJECTIVE: To determine the role of antibiotics in patients with acute pancreatitis. DESIGN: Literature review. METHOD: A Medline search for randomised clinical trials (RCTs) during the period 1990-1999 was carried out using the key words 'pancreatitis', 'acute' and 'antibiotics'. Outcome measures were pancreas-related infection, sepsis and death. RESULTS: Four RCTs were identified. Control groups were not given antibiotics. Based on the pooled data, the differences in risk in favour of the groups treated with various antibiotics were as follows: -14% (95% CI: -26(-)-1; p = 0.04) for pancreas infections, -25% (95% CI: -39(-)-12; p = 0.0002) for sepsis and -13% (95%-BI: -22(-)-3; p = 0.007) for death. CONCLUSION: Administration of antibiotics to patients with severe acute (necrotising) pancreatitis reduces the risk of serious complications.

Molecular detection of antimicrobial resistance.

The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art.

Long-term infectious complications and their relation to treatment duration in catheter-related Staphylococcus aureus bacteremia.

The optimal duration of treatment for catheter-related Staphylococcus aureus bacteremia is not known. Short courses (< or = 2 weeks) of therapy should be viewed with caution because essential data on late complications, such as osteomyelitis and metastatic abscesses, are lacking. This study represents a retrospective analysis of the data from 49 adult patients hospitalised in the period 1994-1996 (mean age, 57 years; range, 20-90 years; 47% male) and from whom Staphylococcus aureus was cultured concomitantly from peripheral blood and catheter segments. Forty-six venous catheters, two arterial catheters, and one unknown type of catheter were used. Forty-four patients were treated with effective anti-Staphylococcus aureus antibiotics. Twenty patients had a favourable outcome, defined as no complication and no death during 1 year of follow-up, 24 patients had complications, 14 patients died due to attributable mortality, and 5 other patients died of an underlying disease without showing signs or symptoms of a complication. Patients were categorised according to the duration of treatment. There were small differences between a shorter (1-14 days) and a longer (>14 days) course of antibiotics with regard to favourable outcome (41% vs. 33%), complications (48% vs. 53%), attributable death (31% vs. 20%), and death due to underlying disease (41% vs. 33%), respectively. The rates of complications and death were high, but a definite conclusion cannot be drawn because the study was underpowered. More randomised trials are needed, but, until the results of such trials are available, the duration of therapy should not be shortened to less than 14 days.