Burden of Surgical Site Infections Associated with Select Spine Operations and Involvement of Staphylococcus aureus.

BACKGROUND: Spine operations may be indicated for treatment of diseases including vertebral injuries, degenerative spinal conditions, disk disease, spinal misalignments, or malformations. Surgical site infection (SSI) is a clinically important complication of spine surgery. Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), is a leading cause of post-spinal SSIs. METHODS: PubMed and applicable infectious disease conference proceedings were searched to identify relevant published studies. Overall, 343 full-text publications were screened for epidemiologic, mortality, health care resource utilization, and cost data on SSIs associated with specified spine operations. RESULTS: Surgical site infection rates were identified in 161 studies from North America, Europe, and Asia. Pooled average SSI and S. aureus SSI rates for spine surgery were 1.9% (median, 3.3%; range, 0.1%-22.6%) and 1.0% (median, 2.0%; range, 0.02%-10.0%). Pooled average contribution of S. aureus infections to spinal SSIs was 49.3% (median, 50.0%; range, 16.7%-100%). Pooled average proportion of S. aureus SSIs attributable to MRSA was 37.9% (median, 42.5%; range, 0%-100%). Instrumented spinal fusion had the highest pooled average SSI rate (3.8%), followed by spinal decompression (1.8%) and spinal fusion (1.6%). The SSI-related mortality rate among spine surgical patients ranged from 1.1%-2.3% (three studies). All studies comparing SSI and control cohorts reported longer hospital stays for patients with SSIs. Pooled average SSI-associated re-admission rate occurring within 30 d from discharge ranged from 20% to 100% (four studies). Pooled average SSI-related re-operation rate was 67.1% (median, 100%; range, 33.5%-100%). According to two studies reporting direct costs, spine surgical patients incur approximately double the health care costs when they develop an SSI. CONCLUSIONS: Available published studies demonstrate a clinically important burden of SSIs related to spine operations and the substantial contribution of S. aureus (including MRSA). Preventive strategies aimed specifically at S. aureus SSIs could reduce health care costs and improve patient outcomes for spine operations.

Burden and Prevention of Adverse Cardiac Events in Patients with Concomitant Chronic Heart Failure and Coronary Artery Disease: A Literature Review.

BACKGROUND: Chronic heart failure (HF) or coronary artery disease (CAD) confers risk for thromboembolism and secondary adverse cardiac events (ACEs) (e.g., mortality, myocardial infarction, and stroke). When HF and CAD occur concomitantly, ACE risk is reported to be elevated. We investigated ACEs, their epidemiology, and the resulting burden among patients with concomitant HF and CAD through a structured review of recent literature. Antithrombotic treatment for ACE prevention was assessed. METHODS: Pertinent databases (PubMed, other) were searched for relevant articles published from January 2004 to March 2015. Data collected included ACE incidence, healthcare resource use, costs, change in quality of life attributed to ACEs, and treatment practice for prevention of ACEs in patients with concomitant HF and CAD. RESULTS: Mortality rates for patients with both HF and CAD ranged from 4.9-12.3% at 30 days to 13.7-86% for periods between 9.9 months and 10 years. Incidence of ACEs among HF patients with CAD is, respectively, at least 82% and 15% higher than for patients without HF or without CAD, except for stroke investigated in two studies. All-cause and HF-related hospitalization is the main driver of the economic burden in patients with HF, the majority of whom had CAD origin. Despite high prevalence of ischemic complications, there is limited evidence to support the use of warfarin-type antithrombotics among HF patients. CONCLUSION: This study confirms that patients with concomitant HF and CAD are at elevated risk for ACEs and suggests the need for effective new antithrombotic treatments to further decrease ischemic complication rates in this population.

The Burden of Major Adverse Cardiac Events and Antiplatelet Prevention in Patients with Coronary or Peripheral Arterial Disease.

BACKGROUND: Patients with a history of a cardiovascular (CV) disease are at high risk of suffering secondary major adverse cardiac events (MACE), namely death, nonfatal myocardial infarction (MI), stroke, symptomatic pulmonary embolism, CV and all-cause hospitalization, and bleeding. METHODS: A comprehensive review of the literature was conducted to review the epidemiology and burden of MACE in patients with coronary or peripheral arterial disease (CAD or PAD) in Europe and other ex-US regions. Relevant articles published between 2003 and 2013 were retrieved from PubMed and other sites. RESULTS: MACE incidence and prevalence in patients with CAD or PAD were increased by at least 1.4-fold compared with matched controls with no CV disease. In patients with CAD, MACE mostly occurred within 30 days of primary percutaneous coronary intervention; incidence decreased with time. Increased oxidative stress in coronary and peripheral arteries, diabetes, and chronic kidney disease were identified as the main risk factors for MACE in patients with CAD and PAD. Registry data showed that, although preventive antiplatelet therapy was prescribed at high rates, a large proportion (9-56%) of patients did not receive treatment. Furthermore, adherence to treatment declined over time, potentially leading to disease worsening. CONCLUSION: Despite gaps in the literature, this assessment showed that MACE's risk is substantial among patients with CAD or PAD and that the use of preventive therapies is suboptimal. Development of additional preventive therapies for these patients is warranted.

Burden of Surgical Site Infections Associated with Arthroplasty and the Contribution of Staphylococcus aureus.

BACKGROUND: Patients undergoing arthroplasty are at considerable risk of experiencing post-operative complications, including surgical site infections (SSIs). In addition to potential economic consequences, SSIs can have a negative impact on patient outcomes and may potentially be life-threatening. Staphylococcus aureus has been consistently shown as the leading cause of SSIs associated with orthopedic surgery, with an important contribution from methicillin-resistant S. aureus (MRSA). This study evaluated the global burden of SSIs among patients undergoing orthopedic surgical procedures, and specifically those undergoing knee and hip arthroplasties. METHODS: An extensive search of PubMed and recent conference proceedings was conducted. English articles published between 2003 and 2013 pertaining to SSI epidemiology, patient outcomes, and healthcare resource utilization and costs were reviewed. RESULTS: Overall, 81 studies were included, mainly from North America and Europe. Median SSI and S. aureus SSI rates, calculated as percentage of all arthroplasty procedures, were 1.7% (range: 0.25%-4.4%; 15 studies) and 0.6% (range: 0.1%-23%), respectively. Median SSI rates were 1.3% (range: 0.05%-19%; 22 studies) after knee arthroplasty, and 2.1% (range: 0.05%-28%; 24 studies) after hip arthroplasty. S. aureus SSI rates ranged from 0.2%-2.4% and 0.18%-3.8% for patients undergoing knee and hip arthroplasty, respectively. The percentage of S. aureus SSIs because of MRSA varied widely within each patient category. SSI-related mortality data (14 studies) showed that in-hospital mortality rates were low (1.2%-2.5%), but increased with time after index arthroplasty procedure (up to 56% over 1 y). Studies assessing healthcare resource utilization (n = 21) revealed that developing post-orthopedic SSIs resulted in a two- to three-fold increase in length of hospital stay (LOS) compared with non-infected patients (median LOS: 18.9 d vs. 6 d for non-SSI patients). Patients with SSIs because of methicillin-resistant staphylococci incurred greater mean LOS compared with SSIs because of methicillin-sensitive organisms. Readmission rates reported in 11 studies indicate a greater likelihood in the presence of SSIs; comparison across studies was not feasible because of differences in data reporting. Consistent with increased healthcare resource utilization (LOS and readmission) associated with SSIs, cost studies (n = 23) revealed that the presence of SSIs was associated with up to three-fold cost increase compared with the absence of SSI across all orthopedic patient categories assessed. CONCLUSIONS: SSIs are associated with increased morbidity, mortality rates, healthcare resource utilization, and costs. Despite the relatively low SSI incidence following orthopedic surgery and specifically arthroplasty, preventive methods, specifically those targeting S. aureus, would serve to minimize costs and improve patient outcomes.

Global availability of data on HPV genotype-distribution in cervical, vulvar and vaginal disease and genotype-specific prevalence and incidence of HPV infection in females.

BACKGROUND: Country-level HPV genotyping data may be sought by decision-makers to gauge the genotype-specific burden of HPV-related diseases in their jurisdiction and assess the potential impact of HPV vaccines. We investigated, by country, the availability of published literature on HPV genotypes in cervical, vaginal and vulvar cancers and intraepithelial neoplasms (CINs, VaINs and VINs) and on prevalence and incidence of genital HPV infections among women without clinically manifest disease. FINDINGS: Primary sources of publications were the PubMed/Medline and EMBASE databases. Original studies or meta-analyses published from 2000, covering genotypes 16 and 18 and at least one of genotypes 31/33/45/52/58, were included. Key exclusion criteria were language not English, cervical lesions not histologically confirmed (cytology only), special populations (e.g., immunocompromised) and, for cervical studies, small population (<50). A total of 727 studies reporting HPV genotype-specific data were identified: 366 for cervical cancers and CINs, 43 for vulvar or vaginal cancers and VINs/VaINs, and 395 and 21 for infection prevalence and incidence, respectively, in general female population samples. A large proportion of studies originated from a small set of countries. Cervical cancer/CIN typing data was scarce for several regions with the highest cervical cancer burden, including Eastern, Middle and Western Africa, Central America, South-East Asia, South Asia, and Eastern Europe. Data for vulvar/vaginal disease was limited outside of Europe and North America. CONCLUSIONS: Although a large body of published HPV genotype-specific data is currently available, data gaps exist for genotype-specific infection incidence and several world regions with the highest cervical cancer burden.

Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

Ischaemic stroke and bleeding rates in 'real-world' atrial fibrillation patients.

Stroke prevention guidelines recommend oral anticoagulants (OAC) for atrial fibrillation (AF) patients at moderate/high risk of stroke, and antiplatelet or no therapy for those at low/moderate risk. Outcomes for AF patients receiving antiplatelet/no therapy in 'real-life' clinical practice were explored. This study compared clinical event rates (stroke/bleeding) for AF patients treated with OAC therapy, antiplatelets or no therapy in usual clinical practice to event rates in OAC-treated AF patients from optimally-monitored 'real-life' settings (anticoagulation clinics). We searched biomedical literature (1994-2010) using PubMed to identify 'real-world' studies of clinical event rates for AF patients receiving OAC therapy, antiplatelets, or no therapy; event rates were extracted for each treatment and setting. We identified 136 studies of thromboembolic events and 86 of bleeding events. Ischaemic stroke rates (30 studies) were higher for AF patients receiving no therapy (median: 4.45/100 person-years; range: 0.25-5.9) or antiplatelet-therapy (median: 4.45/100 person-years; range: 2.0-10) compared to OAC-treated patients monitored in anticoagulation clinics (median: 1.72/100 person-years; range: 0.97-2.00), or from a non-specialized setting (median 1.66/100 person-years; range: 0-4.9). Major bleeding rates (32 studies) for patients receiving antiplatelet/no therapy were similar to OAC-treated patients from both clinical settings. As in randomised clinical trials, AF patients in 'real-world' clinical practice receiving antiplatelet/no therapy have higher rates of ischaemic stroke than OAC-treated patients. Antiplatelet/no therapy was associated with similar bleeding rates to OAC therapy. Increasing utilisation of anticoagulants in clinical practice could improve patient outcomes.

Disease burden and unmet needs for prevention of venous thromboembolism in medically ill patients in Europe show underutilisation of preventive therapies.

It was the aim of this review to assess the incidence of venous thromboembolism (VTE) and current practice patterns for VTE prophylaxis among medical patients with acute illness in Europe. A literature search was conducted on the epidemiology and prophylaxis practices of VTE prevention among adult patients treated in-hospital for major medical conditions. A total of 21 studies with European information published between 1999 and April 2010 were retrieved. Among patients hospitalised for an acute medical illness, the incidence of VTE varied between 3.65% (symptomatic only over 10.9 days) and 14.9% (asymptomatic and symptomatic over 14 days). While clinical guidelines recommend pharmacologic VTE prophylaxis for patients admitted to hospital with an acute medical illness who are bedridden, clear identification of specific risk groups who would benefit from VTE prophylaxis is lacking. In the majority of studies retrieved, prophylaxis was under-used among medical inpatients; 21% to 62% of all patients admitted to the hospital for acute medical illnesses did not receive VTE prophylaxis. Furthermore, among patients who did receive prophylaxis, a considerable proportion received medication that was not in accord with guidelines due to short duration, suboptimal dose, or inappropriate type of prophylaxis. In most cases, the duration of VTE prophylaxis did not exceed hospital stay, the mean duration of which varied between 5 and 11 days. In conclusion, despite demonstrated efficacy and established guidelines supporting VTE prophylaxis, utilisation rates and treatment duration remain suboptimal, leaving medical patients at continued risk for VTE. Improved guideline adherence and effective care delivery among the medically ill are stressed.

Characterization of the proportion of untreated and antiplatelet therapy treated patients with atrial fibrillation.

Despite the efficacy of oral anticoagulants for stroke prevention in atrial fibrillation (AF), evidence suggests that many patients with AF who should be treated with vitamin K antagonists (VKAs) are treated with antiplatelet therapy or remain untreated. The aims of this study were to determine the proportion of patients with AF in each treatment category in clinical practice and to ascertain whether treatment is appropriate for stroke risk. An extensive search of the biomedical research published since 1994 was performed. Studies delineating the treatment of patients with AF were captured. Seventy-eight studies pertaining to the treatment of patients with AF were identified; 56 studies, containing data from 1980 to 2007, met the inclusion criteria. Over time, the use of VKA therapy for stroke prevention increased, while the proportion of untreated patients decreased; antiplatelet use remained static. Looking at the more recent data, (collected from 2000 onward), the proportion of patients receiving no therapy ranged from 4% to 48% (median 18%), antiplatelet therapy from 10% to 56% (median 30%), and VKA therapy from 9% to 86% (median 52%). Although most studies showed a decrease in the proportion of antiplatelet-treated and untreated patients with increasing stroke risk (12 of 14 studies), many patients at moderate or high risk for stroke were not treated according to guidelines. In conclusion, this review shows that up to 56% of patients with AF are treated with antiplatelet therapy, and up to 48% receive no therapy regardless of stroke risk level. This may reflect the inconvenience associated with VKA use, inadequate assessment of stroke risk, or poor adherence to treatment guidelines.

Underuse of oral anticoagulants in atrial fibrillation: a systematic review.

BACKGROUND: Atrial fibrillation is associated with substantial mortality and morbidity from stroke and thromboembolism. Despite an efficacious oral anticoagulation therapy (warfarin), atrial fibrillation patients at high risk for stroke are often under-treated. This systematic review compares current treatment practices for stroke prevention in atrial fibrillation with published guidelines. METHODS: Literature searches (1997-2008) identified 98 studies concerning current treatment practices for stroke prevention in atrial fibrillation. The percentage of patients eligible for oral anticoagulation due to elevated stroke risk was compared with the percentage treated. Under-treatment was defined as treatment of <70% of high-risk patients. RESULTS: Of 54 studies that reported stroke risk levels and the percentage of patients treated, most showed underuse of oral anticoagulants for high-risk patients. From 29 studies of patients with prior stroke/transient ischemic attack who should all receive oral anticoagulation according to published guidelines, 25 studies reported under-treatment, with 21 of 29 studies reporting oral anticoagulation treatment levels below 60% (range 19%-81.3%). Subjects with a CHADS(2) (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >or=2 also were suboptimally treated, with 7 of 9 studies reporting treatment levels below 70% (range 39%-92.3%). Studies (21 of 54) using other stroke risk stratification schemes differ in the criteria they use to designate patients as "high risk," such that direct comparison is not possible. CONCLUSIONS: This systematic review demonstrates the underuse of oral anticoagulation therapy for real-world atrial fibrillation patients with an elevated risk of stroke, highlighting the need for improved therapies for stroke prevention in atrial fibrillation.