Two risk assessments: Evaluating the use of indicator HF183 Bacteroides versus pathogen measurements for modelling recreational illness risks in an urban watershed.

The purpose of this study was to evaluate the performance of HF183 Bacteroides for estimating pathogen exposures during recreational water activities. We compared the use of Bacteroides-based exposure assessment to exposure assessment that relied on pathogen measurements. We considered two types of recreational water sites: those impacted by combined sewer overflows (CSOs) and those not impacted by CSOs. Samples from CSO-impacted and non-CSO-impacted urban creeks were analysed by quantitative polymerase chain reaction (qPCR) for HF183 Bacteroides and eight human gastrointestinal pathogens. Exposure assessment was conducted two ways for each type of site (CSO-impacted vs. non-CSO impacted): 1) by estimating pathogen concentrations from HF183 Bacteroides concentrations using published ratios of HF183 to pathogens in sewage and 2) by estimating pathogen concentrations from qPCR measurements. QMRA (quantitative microbial risk assessment) was then conducted for swimming, wading, and fishing exposures. Overall, mean risk estimates varied from 0.27 to 53 illnesses per 1,000 recreators depending on exposure assessment, site, activity, and norovirus dose-response model. HF183-based exposure assessment identified CSO-impacted sites as higher risk, and the recommended HF183 risk-based threshold of 525 genomic copies per 100 mL was generally protective of public health at the CSO-impacted sites but was not as protective at the non-CSO-impacted sites. In the context of our urban watershed, HF183-based exposure assessment over- and under-estimated risk relative to exposure assessment based on pathogen measurements, and the etiology of predicted pathogen-specific illnesses differed significantly. Across all sites, the HF183 model overestimated risk for norovirus, adenovirus, and Campylobacter jejuni, and it underestimated risk for E. coli and Cryptosporidium. To our knowledge, this study is the first to directly compare health risk estimates using HF183 and empirical pathogen measurements from the same waterways. Our work highlights the importance of site-specific hazard identification and exposure assessment to decide whether HF183 is applicable for monitoring risk.

Loose body following cross-pin fixation for anterior cruciate ligament reconstruction.

We report a case of loosening of a bioabsorbable cross-pin fixation device for anterior cruciate ligament reconstruction. Forty-two months following a bone tendon bone reconstruction of the anterior cruciate ligament, the patient presented with a subcutaneous collection in the medial side of the knee. At subsequent surgery, a RIGIDFIX cross-pin fixator (Mitek, Westwood, MA, USA) was retrieved, intact, from the sterile fluctuant mass around the superomedial aspect of the knee. The graft was stable both radiologically and clinically, and the patient remains symptom free. This case raises concern about the use of this smooth cross-pin fixator and the consequences of backing out and the resultant intraarticular loose body. We suggest consideration of a loose body if the patient becomes symptomatic postoperatively, and early intervention to prevent chondral damage is recommended.

Psychiatrists' use, knowledge and attitudes to first- and second-generation antipsychotic long-acting injections: comparisons over 5 years.

Psychiatrists' attitudes and knowledge about antipsychotic long-acting injections (LAIs) are important given the increasing emphasis on patient choice in treatment and the availability of second-generation antipsychotic (SGA) LAIs. A cross-sectional study of consultant psychiatrists' attitudes and knowledge in North West England was carried out. A pre-existing questionnaire on clinicians' attitudes and knowledge regarding LAIs was updated. Of 102 participants, 50% reported a decrease in their use of LAIs. LAI prescribing was evenly split between first-generation antipsychotic (FGA) and SGA-LAIs. Most regarded LAIs as associated with better adherence (89%) than tablets. A substantial proportion believed that LAIs could not be used in first-episode psychosis (38%) and that patients always preferred tablets (33%). Compared with a previous sample, the current participants scored more favourably on a patient-centred attitude subscale (60.4% vs 63.5%, P = 0.034) and significantly fewer regarded LAIs as being stigmatising and old-fashioned. Reported LAI prescribing rates have decreased in the last 5 years despite an SGA-LAI becoming available and most clinicians regarding LAIs as effective. Most attitudes and knowledge have remained stable although concerns about stigma with LAI use have decreased. Concerns about patient acceptance continue as do negative views about some aspects of LAI use; these may compromise medication choices offered to patients.

Should patients with symptomatic BPH have a trial of medical therapy by their general practitioner prior to referral for urological assessment?

The British Association of Urological Surgeons (BAUS) has recently recommended guidelines for the management of Lower Urinary Tract Sypmtoms by GPs outlining the indications for urological referral. We wished to assess the prescription of medical therapy by GPs in the referrals to our LUTS pre-assessment clinic. 115 consecutive patients were reviewed prospectively, over a three month period. Each patient was assessed for International Prostatic Symptom Score (IPSS) and Bother Score, uroflowometry with post void residual and whether medical therapy had been commenced (D-Blocker or 5-D-Reductase inhibitor). The majority of patients (75%) were classified with moderate symptoms. Only 10% of those with moderate symptoms and 5% of those with severe symptoms were commenced on medical therapy by their GP as recommended by the BAUS guidelines. Only 30 patients (26%) had completed an IPSS form with their GP. The majority of patients referred to our service for assessment of LUTS have at least moderate symptom severity and are not prescribed medical therapy by their GP. Further primary care education with greater emphasis on the BAUS LUTS algorithm prior to referral to an urologist should be encouraged.

Evolution of an organophosphate-degrading enzyme: a comparison of natural and directed evolution.

Organophosphate-degrading enzyme from Agrobacterium radiobacter P230 (OPDA) is a recently discovered enzyme that degrades a broad range of organophosphates. It is very similar to OPH first isolated from Pseudomonas diminuta MG. Despite a high level of sequence identity, OPH and OPDA exhibit different substrate specificities. We report here the structure of OPDA and identify regions of the protein that are likely to give it a preference for substrates that have shorter alkyl substituents. Directed evolution was used to evolve a series of OPH mutants that had activities similar to those of OPDA. Mutants were selected for on the basis of their ability to degrade a number of substrates. The mutations tended to cluster in particular regions of the protein and in most cases, these regions were where OPH and OPDA had significant differences in their sequences.

Differential healing response of bone adjacent to porous implants coated with hydroxyapatite and 45S5 bioactive glass.

This study tested the hypothesis that the rate and the extent of bone formation adjacent to porous, coated Ti-6Al-4V implants are differentially affected by the type of bioactive ceramic coating. Forty-eight rabbits received cylindrical Ti-6Al-4V intramedullary distal femoral implants bilaterally. Implants for the right limbs were coated with 45S5 Bioglass (45S5). Implants used for the left limbs either were coated with tricalcium phosphate/hydroxyapatite (HA) or were left uncoated as controls (CTL). The 45S5-coated implants histologically and biomechanically were compared to HA-coated and CTL implants at 4, 8, 12, and 16 weeks. After 12 and 16 weeks of healing, more bone and thicker trabeculae were measured histomorphometrically within the implant pores for the 45S5-coated implants compared to the HA-coated and CTL implants (p < 0.05). With time the HA-coated and CTL groups exhibited a significant decline in percent of bone and of trabecular thickness (p < 0.05) while the 45S5-coated implants did not. Biomechanical analyses indicated similar shear strengths for all treatment groups. In summary, 45S5-coated implants exhibited greater bone ingrowth compared to HA-coated and CTL implants, and they maintained their mechanical integrity over time.

Secondary fractures of Le Fort I osteotomy.

PURPOSE: To report the ophthalmic complications of Le Fort I osteotomy for the correction of dentofacial deformities and to determine the maximal compressive loads applied during pterygomaxillary separation in a cadaver model. METHODS: Two cases of ophthalmic complications arising after Le Fort I osteotomy are reported. Le Fort I osteotomy was performed on five cadavers. The maximal compressive load applied during pterygomaxillary separation was recorded with a 10 kN (3,000 lbf) load cell of a MTS Mini-Bionix servo-hydraulic machine (MTS, Eden Prairie, MN, U.S.A.). A paired t test was used to compare forces applied to the right and left sides. Computed tomography scans of each specimen were obtained after Le Fort I osteotomy to document secondary fractures. The skulls were subsequently stained with 1% fuschin red to highlight secondary fractures. RESULTS: Maximum compressive loads during pterygomaxillary separation ranged from 22 N (5.0 lbf) to 162 N (36.5 lbf), with an average of 106 N (23.8 lbf) (SD 47.6 N [10.7 lbf]). Forces applied on the first operative side were significantly greater than forces applied on the second operative side (p = 0.0034). Secondary fractures were found in three specimens by computed tomography and in two specimens by 1% fuschin red. All secondary fractures occurred on the second operative side. CONCLUSION: Secondary fractures in the Le Fort I osteotomy procedures occurred on the side opposite the greater maximal compressive load and on the second operative side.

Biomechanical evaluation of the dynamic hip screw with two- and four-hole side plates.

OBJECTIVES: To determine the biomechanical strength and stiffness of a dynamic hip screw (DHS; Synthes USA, Paoli, PA, U.S.A.) with a two-hole side-plate as compared with a four-hole side-plate design for the reconstruction of unstable three-part intertrochanteric fractures. DESIGN: Eight matched pairs of embalmed human femurs were tested in two modes: (a) 2,000 cycles of simulated physiologic loading; (b) test to failure. SETTING: Laboratory. Simulated single leg stance using a simulated pelvic loading mechanism with abductor loading. Strain and displacement sensors were used to measure fragment shear and distraction and surface strain in the proximal side plate. SPECIMENS: Eight pairs of skeletonized embalmed cadaveric specimens were selected on the basis of femoral neck angle and absence of old fracture, anatomic anomaly, or pathology. INTERVENTION: The specimens were divided into two groups: (a) left femurs received the two-hole side-plate design; (b) right femurs received the four-hole side-plate design. All fractures were reconstructed by the same surgeon using the manufacturer's instructions. MAIN OUTCOME MEASUREMENTS: Implant placement was verified by radiographic measurement of tip-to-apex distance. In cyclic testing, the amount of femoral neck fragment migration in both distraction and shear was quantified. Strain magnitude in the side plate was measured in both cyclic and failure testing. The peak load withstood by the reconstruction was quantified in the failure test. RESULTS AND CONCLUSIONS: Peak load in the failure test was not found to be statistically different between the two-hole and four-hole designs. In cyclic testing, the two-hole configuration exhibited statistically smaller fragment migration in both shear and distraction than the four-hole design (p < 0.05). The strain magnitude in the side plate was not statistically different in the cyclic or failure tests. The femurs with a greater neck angle failed by crushing of the bone in the neck. The femurs with a lesser neck angle failed due to bending of the hardware. The results of this investigation revealed that the two-hole DHS is biomechanically as stable as the four-hole DHS in cyclic and failure loads under the conditions tested. These results, in concert with clinical experience, can be used to support the use of the two-hole DHS for the reconstruction of intertrochanteric fractures without a diaphyseal extension.

The kinetic and structural characterization of the reaction of nafamostat with bovine pancreatic trypsin.

Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, is active against a number of the serine proteases involved in coagulation. This has been proposed as the basis of its anticoagulant activity. We investigated the reaction of Nafamostat with bovine pancreatic trypsin as a model system. It was shown to act as a time-dependent competitive inhibitor, and the inhibition constants for the binding of Nafamostat to trypsin (i.e., Ki) and the overall inhibition constants (i.e., Ki*) were calculated to be 11.5 microM and 0.4+/-0.14 nM, respectively. The second-order rate constant for the reaction was 4.5+/-0.19x10(5) M(-1)s(-1), and the product released following the acylation step, 6-amidino2-naphthol, showed mixed-type inhibition. The competitive (Kic) and uncompetitive (Kiu) inhibition constants were 14.7 microM and 19.5 microM, respectively. Formation of the acyl-enzyme intermediate was dissected into at least two steps, with rates of 0.9 s(-1) and 195 s(-1). The deacylation step was relatively much slower (3.2+/-0.19x10(-5) s(-1), enabling the mass spectroscopic analysis of the acyl-enzyme intermediate, which confirmed the covalent attachment of 4-guanidinobenzoic acid to trypsin. The product of the deacylation step, 4-guanidinobenzoic acid, showed no inhibition up to a concentration of 200 microM. These data strongly suggest that while Nafamostat is a potent inhibitor of trypsin, it is actually an extremely poor substrate, and that apparent inhibition is due to the competitive formation of a very stable acyl-enzyme intermediate, analogous to some other active site titrants.

Mechanical strength of fracture callus in osteopenic bone at different phases of healing.

OBJECTIVES: To quantify and compare peak bending force and stiffness of fractured femurs during healing of ovariectomized (OVX) and sham-operated (SHAM) rats. DESIGN: Temporal biomechanical animal study. SETTING: Rat femurs were fractured and surgically fixed by a qualified surgeon. The inherent instability of the fixation system employed produced delayed union of the fracture. All biomechanical assessments were performed with servohydraulic test machines (Instron Inc., Canton, MA, U.S.A.; and MTS Corp., Eden Prairie, MN, U.S.A.). INTERVENTION: OVX was performed sixteen weeks before femur fracture, and the effect of OVX on healing fractures was determined. MAIN OUTCOMES: Peak bending force and stiffness of the healing femurs at four, six, and eight weeks after fracture. RESULTS: Peak bending loads of the healing fractured femurs in the OVX and SHAM animals were not significantly different. Peak bending loads for the OVX animals at four and six weeks were significantly lower than the peak load at eight weeks (p < 0.05), whereas no difference was found in the peak load with respect to time for the SHAM animals. Both SHAM and OVX animals had greater bending stiffness of the healing fractured femur after eight weeks of healing than at four weeks (p < 0.05). CONCLUSIONS: OVX is known to reduce cancellous bone mass and strength, but the effect of OVX on healing of fractures in cortical bone is controversial. This study, using a delayed-union model, found no significant differences between OVX and SHAM animals in the breaking strength of healing fractures.

Bone histomorphometric and biomechanical abnormalities in mice homozygous for deletion of the dopamine transporter gene.

Dopamine (DA) has been reported to have effects on calcium and phosphorus metabolism. The dopamine transporter (DAT) is believed to control the temporal and spatial activity of released DA by rapid uptake of the neurotransmitter into presynaptic terminals. We have evaluated the histologic and biomechanical properties of the skeleton in mice homozygous for deletion of the DA transporter gene (DAT) to help delineate the role of DA in bone biology. We have demonstrated that DAT-/-mice have reduced bone mass and strength. DAT-/- animals had shorter femur length and dry weight. Ash calcium content of the femur was 32% lower in the DAT-/- mice than in the wild-type animals. Cancellous bone volume in the proximal tibial metaphysis was significantly lower in the DAT-/- animals (p < 0.04). There was a 32% reduction in trabecular thickness (p = NS). For the vertebrae, cancellous bone volume was again lower in the DAT-/- animals compared with wild-type as a consequence of increased trabecular spacing (p < 0.05) and reduced trabecular number (p < 0.05). Cortical thickness and bone area in the femoral diaphysis were reduced in the DAT-/-animals. The ultimate bending load (femoral strength) for the DAT-/- mice was 30% lower than the wild-type mice (p = 0.004). Thus, deletion of the DAT gene results in deficiencies in skeletal structure and integrity.

Effect of bioactive glass particle size on osseous regeneration of cancellous defects.

The bioactive glass known as Bioglass or Perioglass (USB) (US Biomaterials, Alachua, FL) has proven to be an effective graft material owing to the apatite layer which forms on the surface of the glass, promoting bone formation. USB particles range in size from 90 to 710 microns in diameter, as determined by optical microscopy. A similar bioactive material, BioGran (OV) (Orthovita, Malvern, PA), was developed to limit the particle size of 4555 to the range between 300 and 360 microns, as determined by sieving. The objective of this study was to histologically and biomechanically compare the 4555 bioactive glass, produced by US Biomaterials, in a wide particle range (USB) to the narrower particle range glass produced by Orthovita (OV) The grafted defects will then be compared to normal cancellous bone (NORM) of the distal femur in rabbits. Histologically, more bone was quantified at both 4 and 12 weeks within the defects filled with USB and NORM when compared to the limbs filled with OV (p < 0.05). The OV particles had greater particle axes and larger particle areas on average than the USB particles (p < 0.05). However, the particle axis and area of the two materials decreased with time at a similar rate. Biomechanically, the USB- and OV-grafted defects had comparable peak compressive load, compressive stiffness, and compressive modulus which were equivalent to normal bone.

Biomechanical assessment of compression screws.

A series of mechanical tests on anatomic specimen cancellous bone and cancellous bonelike foam were conducted to evaluate and compare an Acutrak compression screw with an AO 4-mm cancellous screw and the Herbert screw. The Acutrak and AO screws produced similar fragment compression in foam and bone; Acutrak and AO compression were significantly greater than that of the Herbert screw. However, Acutrak was able to maintain compression after cyclic loading significantly better than were the AO and Herbert screws. The pushout force of Acutrak and AO screws were significantly greater than that of the Herbert screw in foam and bone. The torque required to break fragment contact was significantly greater for the Acutrak than for the AO or Herbert screws, but that for the AO was greater than that for the Herbert screw. The results of this analysis show the Acutrak screw is capable of producing and maintaining compression between bone fracture fragments. In addition, the Acutrak screw was shown to have superior mechanical characteristics than did Herbert screw in every mode tested. The Acutrak screw did not surpass the fragment compression achieved by the AO screw in foam, but it did not overtighten or experience degradation of compression after 500 cycles of simulated physiologic loading.

An adaptable head retention and alignment device for computed tomography scanning of Macaca mulatta.

An adaptable retention device has been developed for the purpose of holding and aligning the head of a sedated primate subject during computed tomography (CT) scan procedures. The device is used to obtain a close reproduction of CT scan studies at a time before and after dental implant placement in the mandibles of nine subjects. Geometric and material properties are extracted from these studies for the purpose of developing finite elements computer models. The device is constructed of low-density acrylic and consists of a horizontal base to which lateral supports are affixed. The device is placed on the CT table and axially aligned with the scan beam. Repeatable, calibrated CT studies of primate implant subjects were possible using the head holding device.

Finite element analysis of two-abutment Hader bar designs.

Parametric three-dimensional finite element studies were conducted on the Hader bar to determine mechanical properties with respect to bar length, stiffener height, and material properties. Three bar lengths (6, 12, and 18 mm) were analyzed with a 1-mm stiffener height. For the longest bar length (18 mm), two additional stiffener heights were evaluated (2 and 3 mm). In addition, three material types were studied for each of the design cases which represented a selection of alloys commonly used clinically. The model consisted of a representative Hader bar which was constructed of a bar of 1.8 mm diameter. The ends of the bar were fixed to a 2.5-mm diameter coping which was attached to a 1.8-mm diameter root form-type implant, rigidly fixed in a representative block of bone. The bone was modeled as fixed at its distal end to eliminate rigid body motion. A 200-Newton occlusal force was modeled as being transmitted through one, two, or three attachment clips, 5 mm in length, for the three respective bar lengths. The results of these analyses did not predict yielding (failure) for any of the cases studied. Span length and stiffener height were found to play a stronger role in the adequacy of the overall design as compared with changing material properties in the range of alloy stiffness tested. For the span length studies, factors of safety, with respect to static yield strength, ranged from 2.93 to 10.3 and fatigue factors of safety ranged from 1.41 to 3.36.(ABSTRACT TRUNCATED AT 250 WORDS)

Finite element analysis of four-abutment Hader bar designs.

Three-dimensional finite element analyses were conducted on the four-abutment Hader bar to determine mechanical properties with respect to bar length, stiffener height, and material properties. Three stiffener heights (1, 2, and 3 mm) were analyzed representing a clinical range of usage. Three material types were studied which represent a selection of alloys commonly used clinically. The model consisted of a representative Hader bar of 1.8-mm diameter with a 1-mm inferior stiffener. The ends of the bar were fixed to a 5-mm diameter coping which was attached to a 3.8-mm root form-type implant fixed in a representative block of bone. The bone was modeled as fixed at its distal end to eliminate rigid body motion. A 200 Newton occlusal force was imposed on the mesial bar and a 450 Newton force on the distal bar for the three stiffener heights. The results of these analyses predicted yielding and fracture (failure) for all 1-mm stiffener height and type IV gold alloy cases studied. Stiffener height was found to play a strong role in the adequacy of the overall design as compared with changing material properties in the range of alloy stiffness tested. Factors of safety with respect to static yield strength ranged from 1.44 to 2.12 on the distal portion.

The Leeds-Keio prosthesis in chronic anterior cruciate deficiency.

A woven polyester graft is used in chronic anterior cruciate instability. Twenty-five patients were reviewed with an average follow-up period of almost five years. The patients were assessed in terms of function, clinical examination, and residual laxity. The results showed that four could be classified as excellent, 16 good, and four poor. Fifty-two percent of patients returned to their preaccident level of activity, and there did not appear to be any evidence of increasing laxity with time. All patients had a good range of flexion with no extension loss. This prosthesis, along with its unique method of fixation, offers a simple alternative to patellar tendon or soft tissue reconstructions in the chronic anterior cruciate-deficient knee.

Measurement and standards in continuous quality improvement.

So where does all of this lead us? Many QA professionals are currently concerned that CQI will displace their role. Nurses are concerned that they will have to learn an entirely new process and language. In a National Association of Quality Assurance Professionals position paper, Martin (1990) points out that CQI builds on and strengthens the weaknesses of traditional quality assurance approaches. Quality improvement is not a substitute for quality assurance; it is a supplement to expand health care providers' understanding of the components of excellent patient care. Change and variation surrounds us at all times. Continuous quality improvement teaches the premises of variation and change. Through a better understanding of variation and application of this understanding to continuous improvement of the system of care, we will help assure better outcomes for our clients. Nurse administrators and staff nurses should endorse the arrival of continuous quality improvement. As leaders in QA, we are indeed positioned to become leaders in CQI.