Covid-19 and orthopaedic trauma: Quantification of orthopaedic trauma workload and staff resource allocation during a global pandemic-related lockdown.

Introduction: Healthcare systems across the world have struggled as a result of the Covid-19 pandemic. Most specialties have redeployed their staff and resources to deal with the pandemic whilst ceasing their planned elective activity. However acute specialties such as Trauma and Orthopaedics still have a significant emergency caseload that must be safely managed, even in a pandemic. The aim of this study was to investigate the change in Orthopaedic Trauma caseload in a Trauma Unit and a Major Trauma Centre during a pandemic compared to pre-pandemic levels and the associated staffing requirements. Methods: The data presented was collected from a Trauma Unit and a Major Trauma Centre in the United Kingdom. We compared the number of accident and emergency referrals, fracture clinic appointments, inpatient admissions and operations during the six weeks of the first lockdown from 23rd March to May 3, 2020, to the same time period in 2019. Results: The results showed that the orthopaedic trauma caseload was approximately half that of pre-pandemic levels, reducing by an average of 54.2%. Conclusion: A significant orthopaedic trauma caseload still remains to be safely managed during a pandemic and appropriate resources must be allocated. Staff allocation must take into account sick cover and staff wellbeing. A proportion of staff may need to be ring fenced from redeployment to facilitate this.

A More Atherogenic Lipoprotein Status Is Present in Adults With Type 2 Diabetes Mellitus Than in Those Without With Equivalent Degrees of Hypertriglyceridemia.

OBJECTIVES: The impact of type 2 diabetes (T2DM) on biomarkers denoting lipoprotein compositional status was studied in mild and moderate hypertriglyceridemia (HTG). Diabetic dyslipidemia pathophysiology could contribute to differences in lipoprotein compositional status, which could be reflected in the preferred cardiovascular disease risk prediction markers in HTG: non-high-density lipoprotein cholesterol (non-HDLC) and apolipoprotein B (apoB). METHODS: A total of 2,775 fasting lipid profiles from a tertiary care lipid clinic were analyzed as 2 subgroups (with and without T2DM), stratified by triglyceride (TG) levels: normotriglyceridemia (TG 0.01 to 1.7 mmol/L), mild HTG (TG 1.71 to 5 mmol/L) and moderate HTG (TG 5.01 to 10 mmol/L). The mean non-HDLC:apoB ratio in each TG stratum and subgroup was analyzed. We also used linear regression to assess the correlation between non-HDLC and apoB. RESULTS: The mean non-HDLC:apoB ratio was increased in both subgroups in patients with mild and moderate HTG, compared to those with normotriglyceridemia. In moderate HTG, the mean non-HDLC:apoB ratio in the subgroup with T2DM was significantly lower than the subgroup without T2DM. In mild and moderate HTG, the subgroup with T2DM had a stronger correlation between non-HDLC and apoB than did the subgroup without T2DM. DISCUSSION AND CONCLUSIONS: In mild and moderate HTG, adults with T2DM exhibit lipid profiles that represent a different and more atherogenic lipoprotein compositional status, when compared with adults without T2DM. For the same severity of HTG, the lipoprotein compositional status in diabetic dyslipidemia suggests that there is increased abundance of smaller non-HDL particles and their remnants, which are highly atherogenic.

The use of categorical regression in the assessment of the risks of nutrient deficiency and excess

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies ­ including human, animal, and mechanistic studies ­ thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these out-comes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of cat-egorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

Gram stain microscopy in septic arthritis.

Septic arthritis is a serious condition that can lead to rapid destruction of joint if it is not rapidly diagnosed and treated appropriately. The reported annual incidence is 10 in 100 000 although this increases to 70 in 100 000 in those with risk factors for developing septic arthritis mainly rheumatoid arthritis and immune-compromised patients. The aim of this study is to examine the sensitivity and specificity, and thus the clinical usefulness, of gram stain results. This was a single centre, retrospective case series. All joint aspirates over a three year period from May 2015 to April 2018 were reviewed. The gram stain and final culture results noted. 830 samples were included from both native and replaced joints. Native joints accounted for a total of 701 cases (84%) of the aspirates, whilst those obtained from prosthetic joints 129 (16%). In 74 (9%) cases there was a discrepancy between the gram stain and culture results. The sensitivity of the gram stain in this case series is 22% and the specificity of the test is 99.6%. The clinician should have a low threshold for overlooking a negative gram stain result and place greater emphases on the clinical findings in conjunction with biochemical markers.

Association between aluminum in drinking water and incident Alzheimer's disease in the Canadian Study of Health and Aging cohort.

Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 µg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p = 0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.

Risk of Adverse Cardiovascular Events Following a Myocardial Infarction in Patients Receiving Combined Clopidogrel and Proton Pump Inhibitor Treatment: A Nested Case-Control Study.

BACKGROUND: The clinical implications of potential interactions between proton pump inhibitors (PPIs) and clopidogrel have been debated for over a decade. OBJECTIVE: We assessed the association between combined clopidogrel-PPI treatment and the risk of recurrent myocardial infarction (MI) and three secondary outcomes. PATIENTS AND METHODS: A nested case-control study was conducted within Cerner Corporation's Health Facts® database. A retrospective cohort of patients who experienced a first MI and started clopidogrel treatment was created. Within this cohort, patients experiencing a second MI (cases) were matched with up to five controls. Logistic regression was used to estimate adjusted odds ratios (aORs). Findings were compared with those obtained from models with three negative control exposure drugs: H2 receptor antagonists, prasugrel, and ticagrelor. RESULTS: In total, 2890 recurrent MI cases were identified within 12 months following entry into the cohort of clopidogrel users (N = 52,006). aOR for PPI use versus non-use among clopidogrel users was 1.08 [95% confidence interval (CI) 0.95-1.23]. Similar ORs were obtained for secondary endpoints. A positive association between combined use of clopidogrel/PPIs and increased risk of MI was seen in the group aged 80-89 years (aOR 1.26; 95% CI 1.05-1.51). No associations with MI were observed for (1) H2 receptor antagonist use versus non-use among clopidogrel users or (2) PPI use versus non-use among prasugrel users or among ticagrelor users. CONCLUSIONS: Overall, our findings do not support a significant adverse clinical impact of concomitant clopidogrel/PPI use by patients with MI. Nonetheless, investigation of the possible association seen in those aged 80-89 years may be warranted.

Functional Outcomes Following Surgical Fixation of Paediatric Lateral Condyle Fractures of the Elbow - A Systematic Review.

OBJECTIVE: Lateral humeral condyle fractures are the second most common elbow fractures in children. Both K-wire fixation and screw fixation have been advocated as suitable treatment options for displaced fractures. This study aimed to identify which fixation method was associated with the best functional outcomes. METHODS: A systematic review was conducted. Studies reporting functional outcomes following surgical fixation of lateral condyle fractures were included for review. The primary outcome measure was functional outcome. The secondary outcome measure was major complications. A narrative analysis was undertaken, as meta-analysis was felt to be inappropriate due to the differences between included studies. RESULTS: Ten retrospective non-randomised, comparative studies were eligible and included. No randomised-controlled trials were identified. The highest rate of excellent functional outcomes was seen with screw fixation (120/126 [95%]), compared with K-wire fixation (135/162 [86%]). The incidence of major complications was comparable, with complications in 6/95 (6%) of screw fixations and 6/141 (4%) K-wire fixations. A small sample of data on closed reduction demonstrated excellent functional results in 73 of 76 (96%) of patients. Closed reduction of displaced fractures is associated with a significant learning curve however. CONCLUSION: The evidence was of poor quality and comprised of retrospective case series. This prevented meta-analysis and any firm conclusions being drawn from the available data. Screw fixation may be associated with improved functional outcomes. Complication rates between the two methods are comparable. Further prospective studies are recommended.

Key characteristics of 86 agents known to cause cancer in humans.

Since the inception of the International Agency for Research on Cancer (IARC) in the early 1970s, the IARC Monographs Programme has evaluated more than 1000 agents with respect to carcinogenic hazard; of these, up to and including Volume 119 of the IARC Monographs, 120 agents met the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs provided a review and update of Group 1 carcinogens. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers, and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. Data on biological mechanisms of action (MOA) were extracted from the Monographs to assemble a database on the basis of ten key characteristics attributed to human carcinogens. After some grouping of similar agents, the characteristic profiles were examined for 86 Group 1 agents for which mechanistic information was available in the IARC Monographs up to and including Volume 106, based upon data derived from human in vivo, human in vitro, animal in vivo, and animal in vitro studies. The most prevalent key characteristic was "is genotoxic", followed by "alters cell proliferation, cell death, or nutrient supply" and "induces oxidative stress". Most agents exhibited several of the ten key characteristics, with an average of four characteristics per agent, a finding consistent with the notion that cancer development in humans involves multiple pathways. Information on the key characteristics was often available from multiple sources, with many agents demonstrating concordance between human and animal sources, particularly with respect to genotoxicity. Although a detailed comparison of the characteristics of different types of agents was not attempted here, the overall characteristic profiles for pharmaceutical agents and for chemical agents and related occupations appeared similar. Further in-depth analyses of this rich database of characteristics of human carcinogens are expected to provide additional insights into the MOA of human cancer development.

Overview of biological mechanisms of human carcinogens.

This review summarizes the carcinogenic mechanisms for 109 Group 1 human carcinogens identified as causes of human cancer through Volume 106 of the IARC Monographs. The International Agency for Research on Cancer (IARC) evaluates human, experimental and mechanistic evidence on agents suspected of inducing cancer in humans, using a well-established weight of evidence approach. The monographs provide detailed mechanistic information about all carcinogens. Carcinogens with closely similar mechanisms of action (e.g. agents emitting alpha particles) were combined into groups for the review. A narrative synopsis of the mechanistic profiles for the 86 carcinogens or carcinogen groups is presented, based primarily on information in the IARC monographs, supplemented with a non-systematic review. Most carcinogens included a genotoxic mechanism.

Development of a database on key characteristics of human carcinogens.

A database on mechanistic characteristics of human carcinogenic agents was developed by collecting mechanistic information on agents identified as human carcinogens (Group 1) by the International Agency for Research on Cancer (IARC) in the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. A two-phase process is described for the construction of the database according to 24 toxicological endpoints, derived from appropriate test systems that were acquired from data obtained from the mechanisms sections of the IARC Monographs (Section 4) and a supplementary PubMed search. These endpoints were then aligned with 10 key characteristics of human carcinogens that reflect the broader attributes of these agents relating to the development of cancer in humans. The considerations involved in linking of toxicological endpoints to key characteristics are described and specific examples of the determination of key characteristics for six specific agents (tamoxifen, hepatitis B virus, arsenic, ultraviolet and solar radiation, tobacco smoking, and dioxin) are provided. Data for humans and animals were tabulated separately, as were results for in-vivo and for in-vitro sources of information. The database was constructed to support a separate analysis of the expression of these endpoints by 86 Group 1 carcinogens, in-vivo and in-vitro along with an analysis of the key characteristics of these agents.

A cost effectiveness analysis of interventions to reduce residential radon exposure in Canada.

The objective of this analysis is to estimate the incremental cost effectiveness ratios for the 2012 populations in Canada, each province/territory, and 17 census metropolitan areas, for practical radon mitigation scenarios to reduce residential radon exposures. Sixteen intervention scenarios compare radon mitigation implemented at differing rates in new and existing housing relative to preventive measures installed at construction, using three different radon mitigation thresholds. A period life-table analysis was conducted using data derived from two recent Canadian radon surveys, along with Canadian mortality and quality of life data. Analyses adopted a lifetime horizon and a discount rate of 1.5%. It is practical to reduce residential radon and associated lung cancer mortality in Canada, and the most cost effective scenario at each radon mitigation threshold is the combination of the activation of the preventive measures in new housing and mitigation of existing housing.

Cancer-Related Pain: A Longitudinal Study of Time to Stable Pain Control and Its Clinicodemographic Predictors.

CONTEXT: Multidimensional assessment is pivotal in managing cancer-related pain. OBJECTIVES: The objectives of this study were to determine time to stable pain control (SPC) and identify its baseline clinicodemographic predictors in patients with cancer pain. METHODS: This is a prospective longitudinal study of patients attending a cancer pain clinic. Scheduled clinic attendances and weekly investigator-led phone calls enabled monitoring of patients' daily pain diary, opioid use, and other analgesic interventions. Baseline clinicodemographic variables were examined in survival analyses, which included the construction of accelerated failure time models with time ratios [TRs, (95% CIs)], based on time to SPC (pain intensity ≤3 and <3 breakthrough opioid doses over three consecutive days) for variable categories. RESULTS: Of 319 participants, 22 died before achieving SPC and were censored in the survival analysis. The median survival time (95% CI) to SPC was 22 (19-25) days. In multivariable analysis, compared to their respective reference categories, female sex (P = 0.001), substance abuse (P < 0.001), a neuropathic pain component (P < 0.001), and use of ≥1 adjuvant analgesic (P = 0.022) each had TRs > 1 (1.03-2.54), whereas soft tissue pain (P < 0.001) had a TR = 0.71 (0.62-0.82), reflecting longer and shorter time to SPC, respectively. CONCLUSION: SPC is achievable for most patients with cancer pain. Recognition of strong predictors of time to SPC, such as substance abuse, a neuropathic pain component, soft tissue pain, and current use of adjuvant analgesia, may help to triage care services based on therapeutic need and guide analgesic interventions.

Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents.

The potential association between major adverse cardiovascular events (MACE) and concomitant treatment with proton pump inhibitors (PPIs) and clopidogrel has been debated since 2009. Recent reports, however, suggest that PPIs may increase the risk of MACE independently of clopidogrel. This review evaluates epidemiological findings relevant to the association between PPIs, taken alone or concomitantly with antiplatelets, and the risk of MACE. A systematic review and meta-analysis were conducted. Relevant studies were identified from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials and then screened. Included studies were categorized into three groups: Group A: PPIs versus no PPIs; Group B: combined PPIs and clopidogrel versus clopidogrel alone; Group C: combined PPIs and other drugs versus other drugs. Pooled risk ratios (RRs) were calculated for each outcome of interest in each comparison group. Of the 1667 studies identified, 118 were included in the systematic review, of which 66 were included in the meta-analyses. Among Group A observational studies, RRs for MACE outcomes were statistically significant for some patient populations but not others. Pooled RRs from Group A RCTs were not statistically significant for any outcome. Pooled RRs for Group B observational studies were statistically significant for all-cause mortality and MI, but were diminished in magnitude when pooling was restricted to propensity score matched studies or post hoc analyses of RCTs. Group C studies did not demonstrate an association with MACE. Findings do not consistently support an association between MACE and PPIs when taken alone, or concomitantly with antiplatelets.

Trends in concomitant clopidogrel and proton pump inhibitor treatment among ACS inpatients, 2000-2016.

PURPOSE: The US Food and Drug Administration (FDA) issued three safety announcements between January 2009 and October 2010 warning against concomitant use of clopidogrel and proton pump inhibitors (PPIs) due to a potential drug-drug interaction that may attenuate clopidogrel's antiplatelet activity. This primary objective of this study was to examine trends in concomitant clopidogrel/PPI use among acute coronary syndrome (ACS) inpatients in the US between 2000 and 2016, in relation to the FDA safety communications. METHODS: Adult inpatients with a primary diagnosis of ACS were identified from the Cerner Health Facts® database. The standardized (age, sex, race, and census region) prevalence of clopidogrel use with PPIs was calculated yearly and quarterly. Findings were stratified by PPIs' potential to inhibit clopidogrel's activity and by age. RESULTS: A total of 204,533 inpatients were identified. In 2008, the prevalence of concomitant clopidogrel and PPI treatment was 34.9%, decreasing to 24.4 and 16.4% in 2009 and 2010, respectively, with the decline being similar across age groups. Treatment with inhibiting PPIs (omeprazole and esomeprazole) and clopidogrel has continued to decrease since 2010, with a prevalence of 0.8% in 2016. A similar reduction was not observed with clopidogrel and non-inhibiting PPIs (pantoprazole, lansoprazole, rabeprazole, and dexlansoprazole). During the FDA warning period, the combined treatment with clopidogrel and H2 receptor antagonists, an alternative to PPIs suggested by the FDA, temporarily increased from 7.8% in 2008 to 12.8 and 14.5% in 2009 and 2010, respectively. CONCLUSIONS: Findings suggest that clinical practice recommendations made by the FDA were followed. Further research is needed to determine how changes in drug labels and the availability of new drugs may have influenced the observed trends.

Risk factors associated with the onset and progression of Alzheimer's disease: A systematic review of the evidence.

A systematic review was conducted to identify risk factors associated with the onset and progression of Alzheimer's disease (AD). Moderate and high quality systematic reviews were eligible for inclusion. Primary studies reporting on non-genetic risk factors associated with neuropathologically or clinically confirmed AD were considered. Eighty one systematic reviews reporting on AD onset and 12 reporting on progression satisfied the eligibility criteria. Four hundred and thirty-two relevant primary studies reporting on onset were identified; however, only those published between 2010 and 2012 (n=65) were included in the qualitative synthesis. Several factors including statins, light-to-moderate alcohol consumption, compliance with a Mediterranean diet, higher educational attainment, physically and cognitively stimulating activities, and APOE ε2 appeared to be associated with a decreased risk of AD onset. The evidence was suggestive of an increased risk of AD associated with head injury in males, age, diabetes mellitus, conjugated equine estrogen use with medroxyprogesterone acetate, current smoking, and lower social engagement. With respect to genetic factors, APOE ε4 remained the strongest predictor of AD. Physical and cognitive activities were associated with a beneficial effect on cognitive function and other indicators of dementia progression while higher educational attainment was associated with faster cognitive decline. Although suggestive of an association, the current evidence for a majority of the identified putative factors for AD onset and progression was weak, at best due to conflicting findings across studies or inadequate evidence. Further research is required to confirm the etiological or protective role of a number of risk factors.

Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

Modeling U-Shaped Exposure-Response Relationships for Agents that Demonstrate Toxicity Due to Both Excess and Deficiency.

Essential elements such as copper and manganese may demonstrate U-shaped exposure-response relationships due to toxic responses occurring as a result of both excess and deficiency. Previous work on a copper toxicity database employed CatReg, a software program for categorical regression developed by the U.S. Environmental Protection Agency, to model copper excess and deficiency exposure-response relationships separately. This analysis involved the use of a severity scoring system to place diverse toxic responses on a common severity scale, thereby allowing their inclusion in the same CatReg model. In this article, we present methods for simultaneously fitting excess and deficiency data in the form of a single U-shaped exposure-response curve, the minimum of which occurs at the exposure level that minimizes the probability of an adverse outcome due to either excess or deficiency (or both). We also present a closed-form expression for the point at which the exposure-response curves for excess and deficiency cross, corresponding to the exposure level at which the risk of an adverse outcome due to excess is equal to that for deficiency. The application of these methods is illustrated using the same copper toxicity database noted above. The use of these methods permits the analysis of all available exposure-response data from multiple studies expressing multiple endpoints due to both excess and deficiency. The exposure level corresponding to the minimum of this U-shaped curve, and the confidence limits around this exposure level, may be useful in establishing an acceptable range of exposures that minimize the overall risk associated with the agent of interest.

Modeling U-shaped dose-response curves for manganese using categorical regression.

INTRODUCTION: Manganese is an essential nutrient which can cause adverse effects if ingested to excess or in insufficient amounts, leading to a U-shaped exposure-response relationship. Methods have recently been developed to describe such relationships by simultaneously modeling the exposure-response curves for excess and deficiency. These methods incorporate information from studies with diverse adverse health outcomes within the same analysis by assigning severity scores to achieve a common response metric for exposure-response modeling. OBJECTIVE: We aimed to provide an estimate of the optimal dietary intake of manganese to balance adverse effects from deficient or excess intake. METHODS: We undertook a systematic review of the literature from 1930 to 2013 and extracted information on adverse effects from manganese deficiency and excess to create a database on manganese toxicity following oral exposure. Although data were available for seven different species, only the data from rats was sufficiently comprehensive to support analytical modelling. The toxicological outcomes were standardized on an 18-point severity scale, allowing for a common analysis of all available toxicological data. Logistic regression modelling was used to simultaneously estimate the exposure-response profile for dietary deficiency and excess for manganese and generate a U-shaped exposure-response curve for all outcomes. RESULTS: Data were available on the adverse effects of 6113 rats. The nadir of the U-shaped joint response curve occurred at a manganese intake of 2.70mg/kgbw/day with a 95% confidence interval of 2.51-3.02. The extremes of both deficient and excess intake were associated with a 90% probability of some measurable adverse event. CONCLUSION: The manganese database supports estimation of optimal intake based on combining information on adverse effects from systematic review of published experiments. There is a need for more studies on humans. Translation of our results from rats to humans will require adjustment for interspecies differences in sensitivity to manganese.

Metallosis following full thickness wear in total hip arthroplasty.

Extreme wear through the metal-backed acetabular cup following total hip arthroplasty is rare, as symptoms such as pain and disability will usually manifest earlier. We present the second reported case of extreme wear in a 78-year-old male patient, who presented 20 years following an uncemented total hip replacement with a 3-year history of hip pain, clicking on ambulation and worsening mobility. Radiographs demonstrated that the femoral head had migrated superolaterally through the polyethylene liner and the acetabular cup, and was articulating with the superior wall of the acetabulum causing bony destruction. Metallic fragments were also evident. A review of the current literature on metallosis suggests that should there be any clinical suspicion, blood metal ion levels are monitored and an MARS-MRI scan performed if indicated. If metallosis is detected, then revision surgery can be attempted at an earlier date, where the procedure is not as technically difficult.

Off-label use of cancer therapies in women diagnosed with breast cancer in the United States.

PURPOSE: To determine the level of off-label cancer therapy use in a population of female breast cancer patients and to establish whether this use was evidence-based. METHODS: A study was conducted by sampling Cerner's data warehouse for all women diagnosed with breast cancer between January 2000 and June 2009 who received at least one cancer therapy approved by the US-FDA during the study period. Drug encounters were considered off-label if the circumstances of use did not match the age or medical diagnoses specified on the product label at the time of study. The level of evidence for the use of these drugs in a breast cancer setting was evaluated from randomized phase III trials using a tiered approach. RESULTS: The study included 2,663 women with a median age of 59 years. A total of 1,636 off-label encounters were recorded, representing 13.0% of all encounters. Of the 65 cancer therapies investigated, 55.4% were prescribed off-label. The drugs with the highest off-label use were, in a descending order, vinorelbine, carboplatin, bevacizumab, leuprolide, liposomal doxorubicin and cisplatin. Most off-label encounters were evidence-based and more likely to be associated with private insurance coverage, younger age, ethnicities other than Caucasian, smaller treatment centres and drugs with limited labeled indications that have a longer market history. CONCLUSIONS: Off-label prescribing is common practice in oncology and is an integral component of breast cancer treatment strategies. While this practice tends to be associated with specific socio-demographic factors and disease characteristics, the majority of off-label encounters appear to be evidence-based.