Aims. The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). Patients and Methods. Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. Results. A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the
Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low
Nanometre-sized particles of ultra-high
We have assessed the different adhesive properties
of some of the most common bacteria associated with periprosthetic
joint infection on various types of ultra high
Aims. This study reports the ten-year wear rates, incidence of osteolysis, clinical outcomes, and complications of a multicentre randomized controlled trial comparing oxidized zirconium (OxZr) versus cobalt-chrome (CoCr) femoral heads with ultra-high
Aims. The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. Methods. A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. Results. None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). Conclusion. When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or
Aims. The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on
Aims. As a proven and comprehensive
Aims. Use of
Aims. We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high
Aims. The aim of this prospective cohort study was to evaluate the early migration of the TriFit cementless proximally coated tapered femoral stem using radiostereometric analysis (RSA). Methods. A total of 21 patients (eight men and 13 women) undergoing primary total hip arthroplasty (THA) for osteoarthritis of the hip were recruited in this study and followed up for two years. Two patients were lost to follow-up. All patients received a TriFit stem and Trinity Cup with a vitamin E-infused highly cross-linked ultra-high
The incidence of deep-vein thrombosis and the need for thromboprophylaxis following isolated trauma below the knee is uncertain. We have investigated this with a prospective randomised double-blind controlled trial using low
Aims. We present the ten-year data of a cohort of patients, aged between
18 and 65 years (mean age 52.7 years; 19 to 64), who underwent total
hip arthroplasty. Patients were randomised to be treated with a
cobalt-chrome (CoCr) femoral head with an ultra-high
Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears. Cite this article:
Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome.Aims
Methods
Aims. The primary aim of this study was to compare the wear properties of vitamin E-diffused, highly crosslinked polyethylene (VEPE) and one formulation of moderately crosslinked and mechanically annealed ultra-high
Aims. To evaluate the incidence of primary venous thromboembolism (VTE),
epidural haematoma, surgical site infection (SSI), and 90-day mortality
after elective spinal surgery, and the effect of two protocols for
prophylaxis. Patients and Methods. A total of 2181 adults underwent 2366 elective spinal procedures
between January 2007 and January 2012. All patients wore anti-embolic
stockings, mobilised early and were kept adequately hydrated. In
addition, 29% (689) of these were given low
To analyze the short-term outcome of two types of total wrist arthroplasty (TWA) in terms of wrist function, migration, and periprosthetic bone behaviour. A total of 40 patients suffering from non-rheumatoid wrist arthritis were enrolled in a randomized controlled trial comparing the ReMotion and Motec TWAs. Patient-rated and functional outcomes, radiological changes, blood metal ion levels, migration measured by model-based radiostereometric analysis (RSA), bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), complications, loosening, and revision rates at two years were compared.Aims
Methods
The aim of this study was to compare the migration of the femoral component, five years postoperatively, between patients with a highly cross-linked polyethylene (HXLPE) insert and those with a conventional polyethylene (PE) insert in an uncemented Triathlon fixed insert cruciate-retaining total knee arthroplasty (TKA). Secondary aims included clinical outcomes and patient-reported outcome measures (PROMs). We have previously reported the migration and outcome of the tibial components in these patients. A double-blinded randomized controlled trial was conducted including 96 TKAs. The migration of the femoral component was measured with radiostereometry (RSA) at three and six months and one, two, and five years postoperatively. PROMs were collected preoperatively and at all periods of follow-up.Aims
Methods
Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations.Aims
Methods
Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included.Aims
Methods
The purpose of this study was to assess mid-term survivorship following primary total knee arthroplasty (TKA) with Optetrak Logic components and identify the most common revision indications at a single institution. We identified a retrospective cohort of 7,941 Optetrak primary TKAs performed from January 2010 to December 2018. We reviewed the intraoperative findings of 369 TKAs that required revision TKA from January 2010 to December 2021 and the details of the revision implants used. Kaplan-Meier analysis was used to determine survivorship. Cox regression analysis was used to examine the impact of patient variables and year of implantation on survival time.Aims
Methods
Revision total hip arthroplasty in patients with Vancouver type B3 fractures with Paprosky type IIIA, IIIB, and IV femoral defects are difficult to treat. One option for Paprovsky type IIIB and IV defects involves modular cementless, tapered, revision femoral components in conjunction with distal interlocking screws. The aim of this study was to analyze the rate of reoperations and complications and union of the fracture, subsidence of the stem, mortality, and the clinical outcomes in these patients. A total of 46 femoral components in patients with Vancouver B3 fractures (23 with Paprosky type IIIA, 19 with type IIIB, and four with type IV defects) in 46 patients were revised with a transfemoral approach using a modular, tapered, cementless revision Revitan curved femoral component with distal cone-in-cone fixation and prospectively followed for a mean of 48.8 months (SD 23.9; 24 to 112). The mean age of the patients was 80.4 years (66 to 100). Additional distal interlocking was also used in 23 fractures in which distal cone-in-cone fixation in the isthmus was < 3 cm.Aims
Methods
Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area. Cite this article:
The Vantage Total Ankle System is a fourth-generation low-profile fixed-bearing implant that has been available since 2016. We aimed to describe our early experience with this implant. This is a single-centre retrospective review of patients who underwent primary total ankle arthroplasty (TAA) with a Vantage implant between November 2017 and February 2020, with a minimum of two years’ follow-up. Four surgeons contributed patients. The primary outcome was reoperation and revision rate of the Vantage implant at two years. Secondary outcomes included radiological alignment, peri-implant complications, and pre- and postoperative patient-reported outcomes.Aims
Methods
Isolated acetabular liner exchange with a highly crosslinked polyethylene (HXLPE) component is an option to address polyethylene wear and osteolysis following total hip arthroplasty (THA) in the presence of a well-fixed acetabular shell. The liner can be fixed either with the original locking mechanism or by being cemented within the acetabular component. Whether the method used for fixation of the HXLPE liner has any bearing on the long-term outcomes is still unclear. Data were retrieved for all patients who underwent isolated acetabular component liner exchange surgery with a HXLPE component in our institute between August 2000 and January 2015. Patients were classified according to the fixation method used (original locking mechanism (n = 36) or cemented (n = 50)). Survival and revision rates were compared. A total of 86 revisions were performed and the mean duration of follow-up was 13 years.Aims
Methods
The primary outcome was investigating differences in wear, as measured by femoral head penetration, between cross-linked vitamin E-diffused polyethylene (vE-PE) and cross-linked polyethylene (XLPE) acetabular component liners and between 32 and 36 mm head sizes at the ten-year follow-up. Secondary outcomes included acetabular component migration and patient-reported outcome measures (PROMs) such as the EuroQol five-dimension questionnaire, 36-Item Short-Form Health Survey, Harris Hip Score, and University of California, Los Angeles Activity Scale (UCLA). A single-blinded, multi-arm, 2 × 2 factorial randomized controlled trial was undertaken. Patients were recruited between May 2009 and April 2011. Radiostereometric analyses (RSAs) were performed from baseline to ten years. Of the 220 eligible patients, 116 underwent randomization, and 82 remained at the ten-year follow-up. Eligible patients were randomized into one of four interventions: vE-PE acetabular liner with either 32 or 36 mm femoral head, and XLPE acetabular liner with either 32 or 36 mm femoral head. Parameters were otherwise identical except for acetabular liner material and femoral head size.Aims
Methods
This study compared patient-reported outcomes of three total knee arthroplasty (TKA) designs from one manufacturer: one cruciate-retaining (CR) design, and two cruciate-sacrificing designs, anterior-stabilized (AS) and posterior-stabilized (PS). Patients scheduled for primary TKA were included in a single-centre, prospective, three-armed, blinded randomized trial (n = 216; 72 per group). After intraoperative confirmation of posterior cruciate ligament (PCL) integrity, patients were randomly allocated to receive a CR, AS, or PS design from the same TKA system. Insertion of an AS or PS design required PCL resection. The primary outcome was the mean score of all five subscales of the Knee injury and Osteoarthritis Outcome Score (KOOS) at two-year follow-up. Secondary outcomes included all KOOS subscales, Oxford Knee Score, EuroQol five-dimension health questionnaire, EuroQol visual analogue scale, range of motion (ROM), and willingness to undergo the operation again. Patient satisfaction was also assessed.Aims
Methods
Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan.Aims
Methods
MicroRNAs (miRNAs ) are small non-coding RNAs
that regulate gene expression. We hypothesised that the functions
of certain miRNAs and changes to their patterns of expression may
be crucial in the pathogenesis of nonunion. Healing fractures and
atrophic nonunions produced by periosteal cauterisation were created
in the femora of 94 rats, with 1:1 group allocation. At post-fracture
days three, seven, ten, 14, 21 and 28, miRNAs were extracted from
the newly generated tissue at the fracture site. Microarray and
real-time polymerase chain reaction (PCR) analyses of day 14 samples
revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p, were highly upregulated in nonunion.
Real-time PCR analysis further revealed that, in nonunion, the expression
levels of all five of these miRNAs peaked on day 14 and declined
thereafter. . Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p may play an important role in the development
of nonunion. These findings add to the understanding of the
Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients. Cite this article:
BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems. A total of 53 patients were randomized to be treated using Bi-Metric cementless femoral stems with either only a porous titanium plasma-sprayed coating (P group) or a porous titanium plasma-sprayed coating with an additional BoneMaster coating (PBM group). The patients were examined with radiostereometry until five years after surgery.Aims
Methods
Periosteum is important for bone homoeostasis
through the release of bone morphogenetic proteins (BMPs) and their
effect on osteoprogenitor cells. Smoking has an adverse effect on
fracture healing and bone regeneration. The aim of this study was
to evaluate the effect of smoking on the expression of the BMPs
of human periosteum. Real-time polymerase chain reaction was performed
for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from
45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured
bones (21 smokers, 39 non-smokers). A hierarchical model of BMP
gene expression (BMP-2 >
BMP-6 >
BMP-4 >
BMP-7) was demonstrated
in all samples. When smokers and non-smokers were compared, a remarkable
reduction in the gene expression of BMP-2, -4 and -6 was noticed
in smokers. The comparison of fracture and non-fracture groups demonstrated
a higher gene expression of BMP-2, -4 and -7 in the non-fracture
samples. Within the subgroups (fracture and non-fracture), BMP gene
expression in smokers was either lower but without statistical significance
in the majority of BMPs, or similar to that in non-smokers with
regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In
smokers, BMP gene expression of human periosteum was reduced, demonstrating
the effect of smoking at the
We describe a cohort of patients with a high rate of mid-term failure following Kinemax Plus total knee replacement inserted between 1998 and 2001. This implant has been recorded as having a survival rate of 96% at ten years. However, in our series the survival rate was 75% at nine years. This was also significantly lower than that of subsequent consecutive series of PFC Sigma knee replacements performed by the same surgeon. No differences were found in the clinical and radiological parameters between the two groups. At revision the most striking finding was polyethylene wear. An independent analysis of the polyethylene components was therefore undertaken. Scanning electron microscopy revealed type 2 fusion defects in the ultra-high
The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified.Aims
Methods
Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. Trauma patients are at risk of progressive organ dysfunction from what appears to be an uncontrolled immune response. The availability of improved techniques of
Oxidised zirconium (OxZi) has been developed
as an alternative bearing surface for femoral heads in total hip arthroplasty
(THA). This study has investigated polyethylene wear, functional
outcomes and complications, comparing OxZi and cobalt–chrome (CoCr)
as part of a three-arm, multicentre randomised controlled trial.
Patients undergoing THA from four institutions were prospectively
randomised into three groups. Group A received a CoCr femoral head
and highly cross-linked polyethylene (XLPE) liner; Group B received
an OxZi femoral head and XLPE liner; Group C received an OxZi femoral
head and ultra-high
The aim of this study was to evaluate the performance of first-generation annealed highly cross-linked polyethylene (HXLPE) in cementless total hip arthroplasty (THA). We retrospectively evaluated 29 patients (35 hips) who underwent THA between December 2000 and February 2002. The survival rate was estimated using the Kaplan-Meier method. Hip joint function was evaluated using the Japanese Orthopaedic Association (JOA) score. Two-dimensional polyethylene wear was estimated using Martell’s Hip Analysis Suite. We calculated the wear rates between years 1 and 5, 5 and 10, 10 and 15, and 15 and final follow-up.Aims
Methods
We are grateful to Dr Robert A. Goldstone of Paterson, New Jersey, for pointing out an error in the article by M. R. Colwill and R. H. Maudsley on "The Management of Gas Gangrene with Hyperbaric Oxygen Therapy" in this Journal of November 1968, 50-B, 732. On page 742, the second line should read "They recommend the use of/ow
The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the
We report an audit of 208 patients with a mean age of 39 years (16 to 65) attending the Orthopaedic Assessment Unit at the Wellington Hospital between January 2006 and December 2007 with an injury of the tendo Achillis requiring immobilisation in a cast. Information on assessment of venous thromboembolism (VTE) risk, prophylactic measures and VTE events for all patients was obtained from the medical records. A VTE risk factor was documented in the records of three (1%) patients. One of the 208 patients received aspirin prophylaxis; none received low
Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative. We performed a retrospective review of patients diagnosed with hip or knee PJI between 1 January 2010 and 31 December 2019, at the Mayo Clinic in Rochester, Minnesota, USA. We included patients aged 18 years or older who had fungal, mycobacterial, or both cultures performed together with bacterial cultures. Cases with positive fungal or mycobacterial cultures were reviewed using the electronic medical record to classify the microbiological findings as representing true infection or not.Aims
Methods
Non-tuberculous mycobacterial infections pose a significant diagnostic and therapeutic challenge. We report two cases of such infection of the spine in HIV-negative patients who presented with deformity and neurological deficit. The histopathological features in both specimens were diagnostic of tuberculosis. The isolates were identified as Mycobacterium intracellulare and M. fortuitum by genotyping (MicroSeq 16S rDNA Full Gene assay) and as M. tuberculosis and a mycobacterium other than tuberculosis, respectively, by culture. There is a growing need for
Thromboprophylaxis after elective orthopaedic surgery remains controversial. Recent guidelines from the National Institute for Clinical Excellence (NICE) have suggested that low
We performed a prospective genotype-phenotype study using
This study aimed to answer two questions: what are the best diagnostic methods for diagnosing bacterial arthritis of a native joint?; and what are the most commonly used definitions for bacterial arthritis of a native joint? We performed a search of PubMed, Embase, and Cochrane libraries for relevant studies published between January 1980 and April 2020. Of 3,209 identified studies, we included 27 after full screening. Sensitivity, specificity, area under the curve, and Youden index of diagnostic tests were extracted from included studies. We grouped test characteristics per diagnostic modality. We extracted the definitions used to establish a definitive diagnosis of bacterial arthritis of a native joint per study.Aims
Methods
Aims. There is uncertainty regarding the optimal means of thromboprophylaxis
following total hip and knee arthroplasty (THA, TKA). This systematic
review presents the evidence for acetylsalicylic acid (aspirin)
as a thromboprophylactic agent in THA and TKA and compares it with
other chemoprophylactic agents. Materials and Methods. A search of literature published between 2004 and 2014 was performed
in accordance with Preferred Reporting Items for Systematic Reviews
and Meta-Analyses guidelines. A total of 13 studies were eligible
for inclusion. Results. Evidence from one good quality randomised controlled trial (RCT)
showed no difference in rates of venous thrombo-embolism (VTE) in
patients given aspirin or low