Systematic Analysis of Mobile Genetic Elements Mediating ß-Lactamase Gene Amplification in Noncarbapenemase-Producing Carbapenem-Resistant Enterobacterales Bloodstream Infections.

Noncarbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE) are increasingly recognized as important contributors to prevalent carbapenem-resistant Enterobacterales (CRE) infections. However, there is limited understanding of mechanisms underlying non-CP-CRE causing invasive disease. Long- and short-read whole-genome sequencing was used to elucidate carbapenem nonsusceptibility determinants in Enterobacterales bloodstream isolates at MD Anderson Cancer Center in Houston, Texas. We investigated carbapenem nonsusceptible Enterobacterales (CNSE) mechanisms (i.e., isolates with carbapenem intermediate resistance phenotypes or greater) through a combination of phylogenetic analysis, antimicrobial resistance gene detection/copy number quantification, porin assessment, and mobile genetic element (MGE) characterization. Most CNSE isolates sequenced were non-CP-CRE (41/79; 51.9%), whereas 25.3% (20/79) were Enterobacterales with intermediate susceptibility to carbapenems (CIE), and 22.8% (18/79) were carbapenemase-producing Enterobacterales (CPE). Statistically significant copy number variants (CNVs) of extended-spectrum ß-lactamase (ESBL) genes (Wilcoxon Test; P-value < 0.001) were present in both non-CP-CR E. coli (median CNV = 2.6×; n = 17) and K. pneumoniae (median CNV = 3.2×, n = 17). All non-CP-CR E. coli and K. pneumoniae had predicted reduced expression of at least one outer membrane porin gene (i.e., ompC/ompF or ompK36/ompK35). Completely resolved CNSE genomes revealed that IS26 and ISEcp1 structures harboring blaCTX-M variants along with other antimicrobial resistance elements were associated with gene amplification, occurring in mostly IncFIB/IncFII plasmid contexts. MGE-mediated ß-lactamase gene amplifications resulted in either tandem arrays, primarily mediated by IS26 translocatable units, or segmental duplication, typically due to ISEcp1 transposition units. Non-CP-CRE strains were the most common cause of CRE bacteremia with carbapenem nonsusceptibility driven by concurrent porin loss and MGE-mediated amplification of blaCTX-M genes. IMPORTANCE Carbapenem-resistant Enterobacterales (CRE) are considered urgent antimicrobial resistance (AMR) threats. The vast majority of CRE research has focused on carbapenemase-producing Enterobacterales (CPE) even though noncarbapenemase-producing CRE (non-CP-CRE) comprise 50% or more of isolates in some surveillance studies. Thus, carbapenem resistance mechanisms in non-CP-CRE remain poorly characterized. To address this problem, we applied a combination of short- and long-read sequencing technologies to a cohort of CRE bacteremia isolates and used these data to unravel complex mobile genetic element structures mediating ß-lactamase gene amplification. By generating complete genomes of 65 carbapenem nonsusceptible Enterobacterales (CNSE) covering a genetically diverse array of isolates, our findings both generate novel insights into how non-CP-CRE overcome carbapenem treatments and provide researchers scaffolds for characterization of their own non-CP-CRE isolates. Improved recognition of mechanisms driving development of non-CP-CRE could assist with design and implementation of future strategies to mitigate the impact of these increasingly recognized AMR pathogens.

Predicting outcomes in older patients undergoing vascular surgery using the Hospital Frailty Risk Score.

BACKGROUND: Frailty may explain why some older patients having vascular surgery are at high risk of adverse outcomes. The Hospital Frailty Risk Score (HFRS) has been designed specifically for use with administrative data and has three categories of frailty risk (low, intermediate and high). The aim of this study was to evaluate the HFRS in predicting mortality, and hospital use in older patients undergoing vascular surgery. METHODS: Routinely collected hospital data linked to death records were analysed for all patients aged 75 years or older who had undergone either endovascular or open vascular surgery between 2010 and 2012 in New South Wales, Australia. Multilevel logistic regression models were used to compare outcomes adjusted for patient and procedural factors, with and without frailty. RESULTS: Some 9752 patients were identified, of whom 1719 (17·6 per cent) had a high-risk HFRS. Patients in the high-risk frailty category had an adjusted odds ratio for death by 30 days after surgery of 4·15 (95 per cent c.i. 2·99 to 5·76) compared with those in the low-risk frailty category, and a similarly increased odds of death by 2 years (odds ratio 4·27, 3·69 to 4·95). Adding the HFRS to a model adjusted for age, sex, co-morbidity score, socioeconomic status, previous hospitalization and vascular procedure type improved the prediction of 2-year mortality and prolonged hospital stay, but there was minimal improvement for 30-day mortality and readmission. CONCLUSION: Adjusting for the HFRS in addition to other patient and procedural risk factors provided greater discrimination of outcomes in this cohort of older patients undergoing vascular surgery.

Peripheral artery disease in the lower limbs: The importance of secondary risk prevention for improved long-term prognosis.

BACKGROUND: Patients with lower limb peripheral artery disease (PAD) are at high risk of cardiovascular mortality and morbidity along with limb loss. PAD is underdiagnosed in the community and presents a missed opportunity to prescribe evidence-based secondary prevention therapy. OBJECTIVE: The aim of this article is to summarise key updates in the management of patients with PAD, with particular reference to newly published guidelines. DISCUSSION: PAD continues to be a major contributor to the mortality and morbidity of patients with atherosclerosis in Australia. For patients with chronic limb-threatening ischaemia, revascularisation remains the mainstay of limb salvage, and expedited access to vascular surgery assessment is necessary. Both prescription of, and adherence to, evidence-based secondary prevention therapy is low. A greater emphasis on cardiovascular risk factor modification for all patients with PAD is required to improve long-term outcomes. General practitioners and vascular surgeons can work collaboratively to provide patient-centred, effective care to patients with PAD.

Genetic and pharmacologic modulation of cementogenesis via pyrophosphate regulators.

Pyrophosphate (PPi) serves as a potent and physiologically important regulator of mineralization, with systemic and local concentrations determined by several key regulators, including: tissue-nonspecific alkaline phosphatase (ALPL gene; TNAP protein), the progressive ankylosis protein (ANKH; ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; ENPP1). Results to date have indicated important roles for PPi in cementum formation, and we addressed several gaps in knowledge by employing genetically edited mouse models where PPi metabolism was disrupted and pharmacologically modulating PPi in a PPi-deficient mouse model. We demonstrate that acellular cementum growth is inversely proportional to PPi levels, with reduced cementum in Alpl KO (increased PPi levels) mice and excess cementum in Ank KO mice (decreased PPi levels). Moreover, simultaneous ablation of Alpl and Ank results in reestablishment of functional cementum in dKO mice. Additional reduction of PPi by dual deletion of Ank and Enpp1 does not further increase cementogenesis, and PDL space is maintained in part through bone modeling/remodeling by osteoclasts. Our results provide insights into cementum formation and expand our knowledge of how PPi regulates cementum. We also demonstrate for the first time that pharmacologic manipulation of PPi through an ENPP1-Fc fusion protein can regulate cementum growth, supporting therapeutic interventions targeting PPi metabolism.

Whole-genome sequencing of Staphylococcus epidermidis bloodstream isolates from a prospective clinical trial reveals that complicated bacteraemia is caused by a limited number of closely related sequence types.

OBJECTIVES: The significance of isolating Staphylococus epidermidis from a blood culture is highly heterogeneous, ranging from contamination to an indication of a serious infection. Herein we sought to determine whether there is a relationship between S. epidermidis genotype and clinical severity of bacteraemia. METHODS: S. epidermidis bacteraemias from a prospective, multicentre trial at 15 centres in the United States and one in Spain were classified as simple (including possible contamination), uncomplicated, and complicated. Whole-genome sequencing (WGS) was performed on 161 S. epidermidis isolates, and clinical outcomes were correlated with genotypic information. RESULTS: A total of 49 S. epidermidis sequence types (STs) were identified. Although strains of all 49 STs were isolated from patients with either simple or uncomplicated infection, all strains causing complicated infections were derived from five STs: ST2, ST5, ST7, ST16, and ST32. ST2 and ST5 isolates were significantly more likely to cause uncomplicated and complicated bloodstream infections compared to simple bacteraemia (odds ratio 2.0, 95%CI 1.1-3.9, p 0.04). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteraemia was an independent predictor of complicated bloodstream infection (odds ratio 3.7, 95%CI 1.2-11.0, p 0.02). ST2/ST5 strains carried larger numbers of antimicrobial resistance determinants compared to non-ST2/ST5 isolates (6.34 ± 1.5 versus 4.4 ± 2.5, p < 0.001). CONCLUSION: S. epidermidis bacteraemia was caused by a genetically heterogeneous group of organisms, but only a limited number of STs-particularly multidrug-resistant ST2 and ST5 strains-caused complicated infections.

ICare-ACS (Improving Care Processes for Patients With Suspected Acute Coronary Syndrome): A Study of Cross-System Implementation of a National Clinical Pathway.

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

How common is subsequent central nervous system toxicity in asymptomatic patients with haematologic malignancy and supratherapeutic voriconazole serum levels?

OBJECTIVES: We sought to determine the frequency at which patients with elevated voriconazole (VRC) levels but no clinically evident central nervous system (CNS) toxicity subsequently develop CNS toxicity. METHODS: We retrospectively reviewed the records of adult patients with haematolologic malignancy who had a VRC serum level >5.5 µg/mL at MD Anderson Cancer Center (January 2010 to December 2015). Patients with any documented CNS toxicity at the time the VRC level was obtained or patients whose VRC was discontinued as a response to high VRC level were excluded. Neurologic status was assessed using standard grading scales. Demographic and clinical characteristics, including potentially interacting medications, were correlated with the development of toxicity. RESULTS: We identified 320 such patients (mean age, 57 ± 15 years; 202 male (63%)). Subsequent CNS toxicity was documented in only 16 patients (5%). The most common CNS toxicities were visual disturbances (9/16, 56%), depressed consciousness (5/16, 31%) and cognitive disturbance (4/16, 19%). Patients with CNS toxicity tended to be older than those without (64 ± 8 vs 57 ± 15 y, p 0.08). The use of one or more neurotoxic drugs was common in patients with subsequent CNS toxicity (14/16, 88%). Reduction of VRC dose associated with the high VRC level did not correlate with less subsequent CNS toxicity. CONCLUSIONS: Development of subsequent CNS toxicity is uncommon in haematolologic malignancy patients with elevated VRC levels who had no evidence of toxicity at the time the level was obtained. Automatic reduction of VRC dose out of concern for impending CNS toxicity might not be warranted.

High mortality in younger patients with major osteoporotic fractures.

Data were gathered with regard to mortality after fractures in 1006 younger patients. Results revealed that major osteoporotic fractures of the hip and humerus and drinking alcohol to excess were related to an increased risk of mortality. INTRODUCTION: Major osteoporotic fractures are known to be associated with increased mortality in older individuals. It is less clear whether this also applies to younger patients. METHODS: Date were gathered regarding patient demographics, fracture pattern, mechanism of injury, as well as smoking and alcohol intake at the time of injury in consecutive patients aged between 40 and 55 who presented to a UK trauma centre over a 12-month period. Mortality data was taken from the electronic patient records and was cross referenced with data from the General Registrar Office of Scotland. Cox regression analysis was used to identify independent predictors of mortality after adjusting for confounding factors. RESULTS: The study cohort consisted of 1006 patients, of which 53% were male. The commonest mechanism of injury was a fall. We obtained complete data regarding mortality for all patients at a median of 5.4 years (inter-quartile range 5.1 to 5.6). During this period, 46 patients were identified as being deceased. The overall standardised mortality ratio for the cohort was substantially increased relative to the age and sex matched general population with a ratio of 3.89 (95% confidence intervals (CI) 1.59 to 6.19). Alcohol excess and fractures involving the humerus and the neck of femur were independent predictors of mortality. CONCLUSIONS: Young individuals with hip and humerus fractures have a significantly increased mortality risk after their injury relative to the general population. The results of our study suggest that this may be in part due to a high prevalence of alcohol excess.

Exome capture from the spruce and pine giga-genomes.

Sequence capture is a flexible tool for generating reduced representation libraries, particularly in species with massive genomes. We used an exome capture approach to sequence the gene space of two of the dominant species in Canadian boreal and montane forests - interior spruce (Picea glauca x engelmanii) and lodgepole pine (Pinus contorta). Transcriptome data generated with RNA-seq were coupled with draft genome sequences to design baits corresponding to 26 824 genes from pine and 28 649 genes from spruce. A total of 579 samples for spruce and 631 samples for pine were included, as well as two pine congeners and six spruce congeners. More than 50% of targeted regions were sequenced at >10× depth in each species, while ~12% captured near-target regions within 500 bp of a bait position were sequenced to a depth >10×. Much of our read data arose from off-target regions, which was likely due to the fragmented and incomplete nature of the draft genome assemblies. Capture in general was successful for the related species, suggesting that baits designed for a single species are likely to successfully capture sequences from congeners. From these data, we called approximately 10 million SNPs and INDELs in each species from coding regions, introns, untranslated and flanking regions, as well as from the intergenic space. Our study demonstrates the utility of sequence capture for resequencing in complex conifer genomes, suggests guidelines for improving capture efficiency and provides a rich resource of genetic variants for studies of selection and local adaptation in these species.

Aerosolized ribavirin: the most expensive drug for pneumonia.

Dramatic, overnight cost increases of important orphan and generic medications have recently come under public and government scrutiny. We highlight the case of aerosolized ribavirin, an important antiviral agent in hematopoietic stem cell transplantation which, because of substantial price increases, may now cost more than the transplant procedure itself.

Economic burden of primary compared with recurrent Clostridium difficile infection in hospitalized patients: a prospective cohort study.

BACKGROUND: Few studies have investigated the additional healthcare costs of recurrent C. difficile infection (CDI). AIM: To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only, compared with CDI patients who experienced recurrent CDI. METHODS: This was a prospective, observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes. Total and CDI-attributable hospital length of stay (LOS) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode. FINDINGS: In all, 540 hospitalized patients aged 62±17 years (42% males) with primary CDI were enrolled, of whom 95 patients (18%) experienced 101 recurrent CDI episodes. CDI-attributable median (interquartile range) LOS and costs (in US$) increased from 7 (4-13) days and $13,168 (7,525-24,456) for patients with primary CDI only versus 15 (8-25) days and $28,218 (15,050-47,030) for patients with recurrent CDI (P<0.0001, each). Total hospital median LOS and costs increased from 11 (6-22) days and $20,693 (11,287-41,386) for patients with primary CDI only versus 24 (11-48) days and $45,148 (20,693-82,772) for patients with recurrent CDI (P<0.0001, each). The median cost of pharmacological treatment while hospitalized was $60 (23-200) for patients with primary CDI only (N=445) and $140 (30-260) for patients with recurrent CDI (P=0.0013). CONCLUSION: This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI. Economic costs and healthcare burden increased significantly for patients with recurrent CDI.

Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type 1 variants.

Plasma drug-resistant minority human immunodeficiency virus type 1 variants (DRMVs) increase the risk of virological failure to first-line non-nucleoside reverse transcriptase inhibitor antiretroviral therapy (ART). The origin of DRMVs in ART-naive patients, however, remains unclear. In a large pan-European case-control study investigating the clinical relevance of pre-existing DRMVs using 454 pyrosequencing, the six most prevalent plasma DRMVs detected corresponded to G-to-A nucleotide mutations (V90I, V106I, V108I, E138K, M184I and M230I). Here, we evaluated if such DRMVs could have emerged from apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3G/F (APOBEC3G/F) activity. Out of 236 ART-naive subjects evaluated, APOBEC3G/F hypermutation signatures were detected in plasma viruses of 14 (5.9%) individuals. Samples with minority E138K, M184I, and M230I mutations, but not those with V90I, V106I or V108I, were significantly associated with APOBEC3G/F activity (Fisher's P < 0.005), defined as the presence of > 0.5% of sample sequences with an APOBEC3G/F signature. Mutations E138K, M184I and M230I co-occurred in the same sequence as APOBEC3G/F signatures in 3/9 (33%), 5/11 (45%) and 4/8 (50%) of samples, respectively; such linkage was not found for V90I, V106I or V108I. In-frame STOP codons were observed in 1.5% of all clonal sequences; 14.8% of them co-occurred with APOBEC3G/F signatures. APOBEC3G/F-associated E138K, M184I and M230I appeared within clonal sequences containing in-frame STOP codons in 2/3 (66%), 5/5 (100%) and 4/4 (100%) of the samples. In a re-analysis of the parent case control study, the presence of APOBEC3G/F signatures was not associated with virological failure. In conclusion, the contribution of APOBEC3G/F editing to the development of DRMVs is very limited and does not affect the efficacy of non-nucleoside reverse transcriptase inhibitor ART.

Aortic aneurysm trials in octogenarians: Are we really measuring the outcomes that matter?

PURPOSE: This study is a systematic review to determine the types of outcomes reported in abdominal aortic aneurysm (AAA) studies of patients aged 80 and over. Specifically, it determines the types of patient-centered outcomes reported. METHOD: MEDLINE and EMBASE were searched from 2000 to 2014 for studies on AAA surgery with outcome data on patients aged 80 and over. Outcomes were categorized according to Donabedian's framework for health quality indicators, with further classification as procedural, complication, resource or patient-centered outcome indicators. FINDINGS: Forty studies were reviewed. Patient-centered outcomes were infrequently reported (13%, n=5), with limited outcomes specifically relevant to older patients. No studies reported physical function, activities of daily living or cognition using validated assessment methods. Short-term mortality (95%, n=38) and complications (85%, n=34) were reported most frequently. CONCLUSION: Reporting of aortic surgery outcomes in patients aged 80 and over requires a focus upon outcomes of primary importance to people of this age.

Revisiting the 'bag of bones': functional outcome after the conservative management of a fracture of the distal humerus.

The best method of managing a fracture of the distal humerus in a frail low-demand patient with osteoporotic bone remains controversial. Total elbow arthroplasty (TEA) has been recommended for patients in whom open reduction and internal fixation (ORIF) is not possible. Conservative methods of treatment, including the 'bag of bones' technique (acceptance of displacement of the bony fragments and early mobilisation), are now rarely considered as they are believed to give a poor functional result. We reviewed 40 elderly and low-demand patients (aged 50 to 93 years, 72% women) with a fracture of the distal humerus who had been treated conservatively at our hospital between March 2008 and December 2013, and assessed their short- and medium-term functional outcome. In the short-term, the mean Broberg and Morrey score improved from 42 points (poor; 23 to 80) at six weeks after injury to 67 points (fair; 40 to 88) by three months. In the medium-term, surviving patients (n = 20) had a mean Oxford elbow score of 30 points (7 to 48) at four years and a mean Disabilities of the Arm, Shoulder and Hand score of 38 points (0 to 75): 95% reported a functional range of elbow flexion. The cumulative rate of fracture union at one year was 53%. The mortality at five years approached 40%. Conservative management of a fracture of the distal humerus in a low-demand patient only gives a modest functional result, but avoids the substantial surgical risks associated with primary ORIF or TEA.

Genetic architecture and genomic patterns of gene flow between hybridizing species of Picea.

Hybrid zones provide an opportunity to study the effects of selection and gene flow in natural settings. We employed nuclear microsatellites (single sequence repeat (SSR)) and candidate gene single-nucleotide polymorphism markers (SNPs) to characterize the genetic architecture and patterns of interspecific gene flow in the Picea glauca × P. engelmannii hybrid zone across a broad latitudinal (40-60 degrees) and elevational (350-3500 m) range in western North America. Our results revealed a wide and complex hybrid zone with broad ancestry levels and low interspecific heterozygosity, shaped by asymmetric advanced-generation introgression, and low reproductive barriers between parental species. The clinal variation based on geographic variables, lack of concordance in clines among loci and the width of the hybrid zone points towards the maintenance of species integrity through environmental selection. Congruency between geographic and genomic clines suggests that loci with narrow clines are under strong selection, favoring either one parental species (directional selection) or their hybrids (overdominance) as a result of strong associations with climatic variables such as precipitation as snow and mean annual temperature. Cline movement due to past demographic events (evidenced by allelic richness and heterozygosity shifts from the average cline center) may explain the asymmetry in introgression and predominance of P. engelmannii found in this study. These results provide insights into the genetic architecture and fine-scale patterns of admixture, and identify loci that may be involved in reproductive barriers between the species.

Outcomes following conservative management of spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) is a rare but a serious cause of myocardial ischaemia and infarction that occurs most frequently in younger female patients. The management of this rare condition remains controversial. In this case series we describe the spectrum of outcomes observed following conservative management.

The importance of epidemiological fracture data: injury epidemiology for the non-epidemiologist.

Epidemiological studies enhance clinical practice in a number of ways. However, there are many methodological difficulties that need to be addressed in designing a study aimed at the collection and analysis of data concerning fractures and other injuries. Most can be managed and errors minimised if careful attention is given to the design and implementation of the research.

When does hip fracture surgery fail?

INTRODUCTION: Hip fractures remain the most common orthopaedic injury requiring hospital admission. Failed surgery for any cause carries a higher morbidity, mortality, and healthcare-related cost. The aims of this study were to determine risk factors for surgical complications of hip fracture surgery, when they occurred and their effect on mortality. PATIENTS AND METHODS: From a prospectively collected consecutive database of 795 hip fractures admitted between July 2007 and June 2008, all surgical and non-surgical complications were identified as well as re-operation for any cause and mortality in the 4 years since surgery. RESULTS: Fifty-five (6.9%) patients were found to have developed a surgical complication requiring further intervention. Risk factors included younger age, smoking and cannulated screw fixation. Cannulated screw fixation was associated with a 30.9% rate of re-operation. Post-operative medical complication occurred in 21.8%. It was associated with a 78.5% mortality at 4 years with a median time to mortality of 58 days (95% CI 0-120 days). CONCLUSIONS: Mechanical failure was the most common reason for cannulated screw re-operation. Hip hemiarthroplasty most commonly failed by infection. Inter-trochanteric and sub-trochanteric fracture fixation had very low failure rates. Post-operative medical complications, but not surgical complications, were associated with a higher mortality rate.

The spectrum of fractures in the elderly.

Fractures in patients aged ≥ 65 years constitute an increasing burden on health and social care and are associated with a high morbidity and mortality. There is little accurate information about the epidemiology of fractures in the elderly. We have analysed prospectively collected data on 4786 in- and out-patients who presented with a fracture over two one-year periods. Analysis shows that there are six patterns of the incidence of fractures in patients aged ≥ 65 years. In males six types of fracture increase in incidence after the age of 65 years and 11 types increase in females aged over 65 years. Five types of fracture decrease in incidence after the age of 65 years. Multiple fractures increase in incidence in both males and females aged ≥ 65 years, as do fractures related to falls. Analysis of the incidence of fractures, together with life expectancy, shows that the probability of males and females aged ≥ 65 years having a fracture during the rest of their life is 18.5% and 52.0%, respectively. The equivalent figures for males and females aged ≥ 80 years are 13.3% and 34.8%, respectively.