Patient-related Risk Research Articles

Hypertension and Cognitive Impairment: Kahrizak Elderly Study

Dementia is a major cause of cognitive impairment in the elderly. Numerous studies have investigated the association between hypertension and cognitive disorders in elderly persons, with inconsistent results. The goal of the study was to investigate the association between hypertension at baseline and cognitive impairment after 24 months’ follow-up in the elderly residents of the Kahrizak Charity Foundation (KCF) in Iran. There were 211 elderly residents of KCF aged 65 years or older with a Mini Mental State Examination (MMSE) score greater than 10. The MMSE score was assessed at the end of the study. Blood pressure was measured in all of the participants at the beginning of study. Data were compared between hypertensive and normotensive patients. A total of 63.5% of patients had impaired cognition (61% and 63.9% in normotensive and hypertensive patients, respectively). Cross sectional analysis of baseline data in a multiple regression model has revealed that diastolic high blood pressure was a risk factor for cognitive impairment even after adjustment for confounding factors (odds ratio: 2.42, 95% CI: 1.01-5.78). In the cohort follow-up analysis, the relative risk of cognitive impairment for patients aged 75 years or older with final diagnosis of hypertension was 0.72 (0.57–0.92). The relative risk of patients with systolic high blood pressure and history of hypertension was 19% and 10%, respectively, which was lower than normotensive group but such differences were not significant. High systolic blood pressure in very old persons may have a preventive effect on development and progression of cognitive impairment. However, diastolic high blood pressure perhaps may be a risk factor for cognitive impairment in elderly persons.

Retrospective study of deep surgical site infections following spinal surgery and the effectiveness of continuous irrigation

Surgical site infection (SSI) is an unfortunate and unpreventable complication of any surgical intervention including spinal surgery. Early deep SSI (EDSSI) after instrumented spinal fusion are particularly difficult to manage due to the implanted, and possibly infected, instrumentation. The purpose of this study is to retrospectively review patients who underwent spinal surgery, investigate the rate of EDSSI, identify patient-related and surgery-related risk factors and to assess the effectiveness of continuous indwelling irrigation on the eradication of these infections. A total of 814 patients (319 women and 495 men) who underwent spinal surgery were enrolled. Mean age at the initial surgery was 57.4 years old. Infections that penetrated the deep fascia within 1 month after the initial operation were considered as EDSSI. The rate of EDSSI, causal organisms, infection management and resolution were studied. Furthermore, we examined the patient-related and the operation-related risk factors. An overall incidence of EDSSI of 1.1% was found. In 177 patients with diabetes mellitus (DM), two patients (1.1%) developed EDSSI. In 28 patients receiving chronic haemodialysis (HD), two patients with infections (7.1%) were identified, which was statistically significantly greater than the other patient populations. Both operative time and intraoperative blood loss were significantly greater in patients with EDSSI than in non-infected patients. Furthermore, the rate of EDSSI in patients undergoing instrumented spinal fusion (3.8%) was significantly higher than that in the other patients. In the nine patients who developed EDSSI, the causal organisms were identified and treated by surgical debridement, antibiotic therapy and continuous indwelling surgical site irrigation. All infections resolved, and no recurrence has been observed at final follow-up. Removal of the instrumentation was required in only one patient. Based on our results, we believe that continuous surgical site irrigation is an effective adjunct in the surgical treatment for early SSI following spinal surgery.

P.26 Evaluation of risk factors in women with breast carcinoma who developed venous thromboembolism

P.26 Evaluation of risk factors in women with breast carcinoma who developed venous thromboembolism

Prevention of deep infection in joint replacement surgery

The incidence of deep infection has declined since the early years of joint replacement surgery (Figure 1). Currently, the infection rates are low: around 1% in primary knee replacements and 0.3–0.6% in hip replacements (Phillips et al. 2006, Pulido et al. 2008, Jamsen et al. 2010). However, even prospective surveillance programs may underestimate the infection rates; thus, the true incidence is probably higher (Huotari et al. 2010). Figure 1. The cumulative revision rates (CRRs; the proportion of operated patients who underwent revision with time) with revision for infection as endpoint in consecutive cohorts of primary total knee arthroplasties (TKAs) performed in patients with osteoarthritis ... Deep infection accounts for up to one quarter of early revisions (Dobzyniak et al. 2006, Mulhall et al. 2006). Recent data from the Scandinavian arthroplasty registries show that the proportion of revision operations that are due to infection is increasing (Figure 2). Operating patients with a higher inherent infection risk, such as obese patients and those with diabetes, and emergence of resistant bacterial strains represent additional challenges, and give reason for continuous dedication to prevent deep infection. Figure 2. The proportions of infections, aseptic loosening, instability, and pain for all reasons for revision knee replacements in 1997–2008 in Denmark. Source: the Danish Knee Arthroplasty Register, Annual Report 2009 (available online at www.dkar.dk ... Patient-related infection risk can be reduced e.g. by managing preoperative anemia, glucose control, and elimination of harmful lifestyle factors such as smoking. Morbidly obese patients represent a special risk group. The principles of infection prevention in perioperative management are well-documented, but adherence to the protocols should be improved. Care should be taken regarding timely and appropriate administration of antibiotic prophylaxis. Combining intravenous antibiotics and antibiotic-impregnated cement further reduces deep infection rates. Finally, monitoring of infection rates on a local, national, and even an international scale is an essential part of quality control and is necessary in order to be able to identify weaknesses in current infection prevention practices.

The Semmes Weinstein monofilament examination is a significant predictor of the risk of foot ulceration and amputation in patients with diabetes mellitus

Diabetic peripheral neuropathy is a major complication of diabetes mellitus (DM) and is the leading cause of foot ulceration and lower extremity amputations (LEAs). The purpose of this systematic review is to evaluate current evidence regarding the prognostic value of the Semmes Weinstein monofilament examination (SWME) in predicting foot ulceration and LEA in patients with DM. The MEDLINE/PubMed database was searched through November 2009 for articles pertaining to diabetic foot and SWME with no language or publication date restrictions. Prognostic studies with original data assessing the predictive value of SWME for foot ulceration or LEA in patients with DM were included in the selection. Data were systematically extracted and analyzed by two independent investigators. Absolute risks and relative risks were determined for each study. Of the 863 studies identified, nine articles were relevant, involving 11,007 patients with DM. Six studies were identified that assessed the prognostic value of SWME regarding diabetic foot ulceration. The relative risk for patients with a positive SWME result versus those with a negative result ranged from 2.5 (95% confidence interval [CI], 2.0 to 3.2) to 7.9 (95% CI, 4.4 to 14.3) in the identified studies with follow up between 1 and 4 years. Three of the studies assessed the risk of LEA with a positive SWME result. The relative risk for LEA ranged from 1.7 (95% CI, 1.1 to 2.6) to 15.1 (95% CI, 4.3 to 52.6) with follow-up between 1.5 and 3.3 years. All nine studies found SWME to be a significant and independent predictor of future foot ulceration or likely of future LEA as well in patients with DM. Therefore, SWME is an important evidence-based tool for predicting the prognosis of patients with diabetic foot, thus enabling improved patient selection for early intervention and management. More research should be conducted to elucidate the relationship between SWME and LEA.

Perioperative haemodynamic therapy

To discuss the perioperative monitoring tools and targets for haemodynamic optimization and to assess the influence of goal-directed therapy (GDT) on organ function, complications and outcome in different categories of surgical patients. The choice of perioperative haemodynamic monitoring for GDT depends on the surgery-related and the patient-related risk. Conventional monitoring and minimally invasive approaches can be used for perioperative optimization of low-risk to moderate-risk patients. Thermodilution methods and continuous cardiac output/oxygen transport monitoring are the most reliable techniques for major surgery and high-risk/unstable patients. An important goal of perioperative haemodynamic therapy is to maintain cardiac function and organ perfusion, optimizing the balance between oxygen delivery and consumption. Several studies, using different monitoring tools and end-points, have shown that GDT provides optimal haemodynamic performance, improves organ function, reduces the number of complications and time to ICU and hospital discharge and decreases the mortality rate in high-risk surgical patients. GDT provides a number of benefits in major surgery. Based on adequate monitoring, the goal-directed algorithms facilitate early detection of pathophysiological changes and influence the perioperative haemodynamic therapy that can improve the clinical outcome. The perioperative GDT should be early, adequate and individualized for every patient.

Preoperative Evaluation of Patients with Possible Coronary Artery Disease

During noncardiac surgery, patients may be at risk for developing cardiac events, related to underlying coronary artery disease. Therefore, perioperative cardiac complications remain an area of clinical interest and concern in patients undergoing noncardiac surgery. Over the years, perioperative risk assessment has evolved significantly to detect surgical patients with myocardium at risk due the coronary artery disease. In addition, many efforts have been made to reduce the cardiac risk of patients undergoing noncardiac surgery. The present review article will focus on the definition of high cardiac risk surgery and will discuss patient-related cardiac risk factors. In addition, the preoperative cardiac tests available to detect patients with coronary artery disease and strategies to reduce perioperative cardiac risk, as recommended in most recent perioperative guidelines, will be outlined.

Blood Transfusion and Survival in Cardiac Surgery

Blood Transfusion and Survival in Cardiac Surgery

Prognostic Significance of Intratumoral Blood Vessel Invasion in Pathologic Stage IA Non-Small Cell Lung Cancer

The 5-year survival rate of pathologic stage IA non-small cell lung cancer (NSCLC) is excellent; however, up to 10% of patients with pathologic stage IA NSCLC still relapse postoperatively and die. This study retrospectively analyzed the clinicopathologic features of patients with pathologic stage IA NSCLC to identify the prognostic factors and investigate the effect of a combination of intratumoral vessel invasion and tumor size. From December 1991 to December 2003, 217 consecutive patients with stage IA NSCLC were selected, and disease-free survival (DFS) was analyzed. Intratumoral blood vessel invasion (BVI) was identified as an independent poor prognostic factor (p = 0.0006). The relative risk for patients with BVI was 4.599 times higher than that for patients without BVI (95% confidence interval, 1.913 to 11.056). According to the new T N M system, the difference in DFS between the patients with and without BVI was statistically significant, not only in tumors exceeding 2 cm (T1b with BVI vs T1b without BVI, p = 0.0020) but also in tumors smaller than 2 cm (T1a with BVI vs T1a without BVI, p < 0.0001). The survival curve of T1b patients without BVI was similar to that of T1a patients without BVI (p = 0.0892). Distant recurrence was frequently observed in both T1a and T1b patients with BVI. BVI is an independent poor prognostic factor in patients with pathologic stage IA NSCLC. These T1a and T1b patients with BVI both might benefit from adjuvant chemotherapy.

Long-term outcomes following coronary drug-eluting- and bare-metal-stent implantation

BackgroundAlthough drug-eluting stents (DES) reduce restenosis rates relative to bare-metal stents (BMS), recent reports have indicated that the use of DES may be associated with an increased risk of stent thrombosis. Our study focused on the effect of stent type on clinical outcomes in a “real world” setting. Methods889 patients undergoing percutaneous coronary intervention (PCI) with either DES (Cypher or Taxus; n=490) or BMS (n=399) were enrolled in a prospective single center registry. The outcome analysis covered a period of up to 3.2 years (mean 2.7 years±0.5 years) and was based on 65 deaths, 27 myocardial infarctions, 76 clinically driven target lesion revascularizations (TLR), and 15 angiographically confirmed cases of definite stent thrombosis and was adjusted for differences in baseline characteristics. ResultsIn total 1277 stents (613 BMS and 664 DES) were implanted in 1215 lesions. Despite a significantly different unadjusted death rate (10.1% and 5.1% in BMS and DES patients, respectively; p<0.05), the patient groups did not differ significantly in the risk of myocardial infarction during 2.7 years of follow-up. After adjustment for differences in baseline characteristics between groups, the difference in the cumulative incidence of death did not remain statistically significant (p=0.22). Target lesion revascularizations occurred significantly less frequently in patients with DES compared to individuals after BMS implantation (5.9% and 11.8% in patients with DES and BMS, respectively; p<0.05). The rate of angiographically confirmed stent thrombosis was 2.1% in patients with DES and 1.1% in BMS patients (p=0.31).There was a significantly lower unadjusted event rate (including deaths, myocardial infarction, target lesion revascularization, and stent thrombosis) in patients with drug-eluting stents than in those with bare-metal stents (16.4% and 25.8%, respectively), with 9.4 fewer such events per 100 patients (unadjusted hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46 to 0.87). After adjustment, the relative risk for all outcome events in patients with drug-eluting stents was 0.79 (95% CI, 0.67 to 0.95). However, the adjusted relative risk for death and myocardial infarction did not differ significantly between groups (adjusted relative risk in patients with drug-eluting stents 0.94 (95% CI, 0.77 to 1.37)). ConclusionsIn this real-world population, the beneficial effect of first generation DES in reducing the need for new revascularization compared with BMS extends to more than 2.5 years without evidence of a worse safety profile. The minor risk of stent thrombosis and myocardial infarction within this period after implantation of DES seems unlikely to outweigh the benefit of these stents.

Protective Effects of Angiotensin‐Converting Enzyme Inhibitors in High‐Risk African American Men With Coronary Heart Disease

Angiotensin-converting enzyme (ACE) inhibitors have been extensively used for the treatment of patients with cardiovascular disease, but several concerns have been raised about their efficacy in African American (AA) patients with heart failure, hypertension, and left ventricular hypertrophy. In this study the authors assessed the effect of ACE inhibitors on total and cardiovascular mortality in high-risk AA patients with angiographically proven coronary artery disease (CAD). This was a retrospective analysis of 810 AA men who underwent diagnostic coronary angiography between 1995 and 2003. All patients had demonstrable CAD and had undergone a complete ischemic workup. Follow-up was from 3 to 10 years. ACE inhibitors were administered to 237 patients, while the remaining 537 patients were not taking ACE inhibitors. Patients taking ACE inhibitors had significantly more comorbidities (hypertension, diabetes, left ventricular hypertrophy, heart failure, severe CAD) at baseline, compared with patients not taking ACE inhibitors (P<.05 for all comorbidities). Despite the unfavorable baseline profile, patients taking ACE inhibitors had significantly lower mortality from CAD during follow-up than patients who were not taking ACE inhibitors (P=.006). Stroke mortality rates were similar in both groups. Cox regression analysis showed an 80% higher relative risk in patients not receiving ACE inhibitors. These data indicate a substantial benefit from ACE inhibitor therapy in high-risk AA patients with CAD.

A meta-analysis on the association of HER-2 overexpression with prognosis in human osteosarcoma

Various studies examining the relationship between HER-2 overexpression and clinical outcome in patients with osteosarcoma have yielded inconclusive results. The purpose of the current study was to evaluate the relation of HER-2 status with clinical outcome in osteosarcoma. We conducted a meta-analysis of five studies that evaluated the relation between HER-2 status and 2-year survival. DerSimonian-Laird random effects analysis was used to estimate the effects of HER-2 overexpression on 2-year survival. The combined relative risk in patients with osteosarcoma for 2-year survival was 1.26 (95% confidence interval, 0.50-3.14; P = 0.63). HER-2-positive status tended to be associated with a worse 2-year survival, but the overall results were not formally statistically significant. An unfavourable prognostic effect of HER-2 overexpression in osteosarcoma was evident from the meta-analysis. However, because several studies were excluded by the current eligibility criteria, caution is needed in interpreting the results.

Risk of bevacizumab-associated gastrointestinal perforation in patients with colorectal cancer and noncolorectal cancer

9622 Background: Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor. It is a widely used angiogenesis inhibitor in the treatment of colorectal cancer (CRC) and other solid tumors. Gastrointestinal (GI) perforation is a potentially fatal adverse event associated with bevacizumab, but the risk unclear. This study was conducted to determine the risk of developing GI perforation among CRC and non-CRC patients receiving bevacizumab. Methods: Databases from PUBMED and the Web Science from January 1966 until July 2008 and abstracts presented at the American Society of Clinical Oncology conferences from January 2000 to through July 2008 were searched to identify relevant studies. Eligible studies included prospective phase III clinical trials in which standard anti-neoplastic therapy was administered with and without the use of bevacizumab with available data for GI perforation. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated using fixed or random effect models based upon the heterogeneity of the included studies. Results: A total of 12084 patients with various solid tumors from 14 phase III trials were included for analysis. Among patients receiving bevacizumab, the incidence of GI perforation was 0.8% (95% CI: 0.6–1.1%), and RR was 2.0 (95% CI: 1.1–3.8, p = 0.028) in compared with controls. The risk of GI perforation was significantly increased in patients receiving bevacizumab at 5 mg/kg/week (RR 2.6, 95% CI: 1.0–6.6, p=0.04), but not at 2.5 mg/kg/week (RR=1.5, 95%CI: 0.7–3.3, p=0.3). Among 2151 patients with CRC, the incidence of GI perforation was 0.8% (95% CI: 0.5–1.6%); while for 2.999 patients with non-CRC malignancies, the incidence of GI perforation was 0.7% (95% CI: 0.5–1.1%); The relative risk of GI perforation varied with tumor type, with significantly increased risk observed in patients with CRC (RR = 3.1, 95% CI: 1.2–8.2, p&lt;0.023), but not non-CRC (RR=1.5, 95% CI: 0.67–3.4, p=0.3). Conclusions: There is a significant difference in the risk of developing GI perforation in CRC and non-CRC patients receiving bevacizumab with a higher relative risk in patients with CRC. Further investigation into the etiology of this difference is recommended. No significant financial relationships to disclose.

Laparoscopic renal cryoablation: Risk factor analysis to predict oncologic outcomes with minimum 5-year follow-up

5094 Background: We analysed risk factors to predict oncologic outcomes at 5–11 year after laparoscopic renal cryoablation (LRC). Methods: Between 09/1997 and 010/2008, we performed renal cryoablation in 340 patients. Of these, 102 patients treated before 10/2003 (all laparoscopic) have minimum 5-year follow-up. Follow-up involved MRI imaging on postoperative day 1, 3 months, 6 months, 12 months, and then annually. Cryolesion biopsy was performed at 6-months. All data were prospectively accrued. Results: In the 102 patients with minimum 5-year follow-up, mean age was 66 years. Mean tumor size was 2.3 cm (0.9–5.0 cm). Median ASA score was 3 and mean BMI was 28. Six patients developed locoregional recurrence, 2 had locoregional recurrence with metastases, and 5 had distant metastases without locoregional recurrence. Overall, there were 7 cancer deaths. In the 69 patients with biopsy-proven renal cell cancer (median follow-up 81 mos; range 60–132 mos), 5-year overall, disease-specific, and disease- free survival was 75%, 92%, and 82%, respectively, while 10-year overall, disease-specific, and disease-free survival was 46%, 83%, and 79%, respectively. On multivariate analysis, previous radical nephrectomy for RCC was the only significant predictor for both recurrence- free survival and cancer-specific survival (p = 0.023 and 0.030, respectively). Relative risk of patients who has a history of radical nephrectomy for RCC treatment was 4.1 (95% CIs, 1.2 to 13.4), and 5.4 (95% CIs, 1.2 to 27.7) for disease-free survival and disease-specific survival, respectively. Conclusions: Laparoscopic renal cryoablation is effective oncologic treatment for renal mass in select patients. Disease-specific survival of 92% at 5-years and 83% at 10-years is possible. Preceding radical nephrectomy for RCC treatment was the only independent predicting factor for both disease-free and disease-specific survival. [Table: see text] No significant financial relationships to disclose.

Impaired exercise capacity predicts sudden cardiac death in a low-risk population: Enhanced specificity with heightened T-wave alternans

Aims. Because sudden cardiac death (SCD) is due to cardiac electrical instability, we postulated that prediction of this mode of death by exercise capacity will be enhanced by combined assessment with T-wave alternans (TWA), an index of repolarization abnormality.Material and methods. The Finnish Cardiovascular Study enrolled consecutive patients (n=2,044) with a routine clinically indicated exercise test. Exercise capacity was measured in metabolic equivalents (METs) and TWA by time-domain modified moving average method.Results. During 47.2±12.8-month follow-up (mean±SD) 120 patients died; 58 were cardiovascular deaths, and 29 were SCD. In multivariate analysis after adjustment for sex, age, smoking, use of β-blockers, as well as other common coronary risk factors, the relative risk of patients whose exercise capacity was depressed (MET < 8) was 8.8 (95% CI 2.0–38.9, P=0.004) for SCD. The combination of low exercise capacity (MET < 8) and elevated TWA (≥65 µV) yielded relative risks for SCD of 36.1 (6.3–206.0, P<0.001), for cardiovascular mortality of 21.1 (6.7–66.2, P<0.001), and for all-cause mortality of 7.8 (3.5–17.4, P<0.001) over patients with neither factor.Conclusions. Reduced exercise capacity, particularly in combination with heightened TWA, indicating enhanced cardiac electrical instability, powerfully predicts risk for SCD in patients referred for exercise testing.

Atherosclerotic Peripheral Vascular Disease Symposium II

Percutaneous intervention for peripheral artery disease has evolved from balloon angioplasty for simple focal lesions to multimodality techniques that enable treatment of severe arterial insufficiency. This technological expansion comes without a standard approach or algorithm, which makes the decision-making process more subjective than objective. Nevertheless, clinical tools are available that can have a favorable effect on patient care, and these promote usage. So, when are standard endovascular techniques (such as balloon and stents) good enough, and when are the latest advances (eg, atherectomy, drug-eluting stents) more appropriate? This section will address these questions for acute limb ischemia (ALI) and chronic critical limb ischemia (CLI). It will also delineate the problem of restenosis, particularly of the superficial femoral artery (SFA), and describe treatment alternatives. The discussion will review the role of drug-eluting stents, atherectomy devices, reentry catheters, and brachytherapy, as well as their potential complications and appropriate remedies. Treatment algorithms for aortoiliac and infrainguinal disease are provided in Figures 1 through 3⇓⇓. Figure 1. Treatment algorithm for acute lower-limb ischemia. *Short infusion of thrombolytic therapy proximal to occlusion can be used to facilitate wire traversal. Figure 2. Simplified treatment algorithm for symptomatic aortoiliac disease in patients deemed candidates for revascularization. In patients with multilevel disease, the aortoiliac segment should be addressed first. TASC indicates TransAtlantic Inter-Society Consensus; AI, aortoiliac; PTA, percutaneous transluminal angioplasty; PE, physical examination; ABI, ankle-brachial index; and U/S, ultrasound. Figure 3. Simplified treatment algorithm for symptomatic infrainguinal peripheral arterial disease, assuming concomitant aortoiliac disease has been treated and the patient is an acceptable candidate for revascularization. *Alternative therapies to PTA include cryotherapy, atherectomy (directional, rotational, ablative), and cutting balloon. †Alternative stent options include stent (graft, balloon expanding, and self expanding) and drug-eluting stent. PTA indicates percutaneous transluminal angioplasty; TASC, TransAtlantic Inter-Society Consensus; PE, physical examination; …

Venous thromboembolism and subsequent hospitalisation due to acute arterial cardiovascular events: A 20-year cohort study

Conclusion: Patients with venous thromboembolism (VTE) have an increased long-term risk of arterial cardiovascular events. Summary: There are conflicting data with respect to whether VTE is associated with an increased risk of arterial cardiovascular events. To help clarify discrepant studies in previous publications, the authors sought to investigate the risk of arterial cardiovascular events in patients with VTE. This was a 20-year population-based cohort study. Data were obtained from nationwide Danish medical databases. Patients with known cardiovascular disease were excluded from this study. The authors then assessed the risk of stroke and myocardial infarction (MI) in 25,199 patients with deep venous thrombosis (DVT), 16,925 patients with pulmonary embolism (PE), and 163,566 controls. In patients with DVT, the relative risks (95% confidence interval) were 1.6 (1.35-1.91) for MI and 2.19 (1.85-2.60) for stroke ≤1 year after the thrombotic event. Similarly, in patients ≤1 year after a PE, the relative risks were 2.60 (2.14-3.14) for MI and 2.93 (2.34–3.66) for stroke. During the next 20 years of follow-up, patients with VTE had 20% to 40% increased risk for arterial cardiovascular events. There was no difference in relative risk in patients with provoked vs unprovoked DVT and PE. Comment: The etiology for the apparent association of atherosclerotic events with VTE is unclear. With the exception of obesity, there is not consistent evidence that venous and atherosclerotic diseases share common risk factors. Perhaps a common prothrombotic mechanism, such as endothelial damage or inflammation, accounts for a potential shared etiology between VTE and arterial ischemia. There are, after all, other conditions such as hyperhomocysteinemia and antiphospholipid antibody syndrome that exemplify disorders that have both arterial and venous thromboembolic features.

Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis

To outline recent research findings with nonmethotrexate disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative arthritis spanning systematic reviews, randomized controlled trials, observational clinical practice trials and assessments of adverse effects. Systematic reviews show no important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disease-modifying antirheumatic drug therapy reduces erosive progression. Observational studies show that nonmethotrexate disease-modifying antirheumatic drugs are widely prescribed; their usage has increased in the biologic era. A systemic review also showed patients who failed monotherapy benefited from disease-modifying antirheumatic drug combinations without excess toxicity. Randomized controlled trials of intensive initial disease-modifying antirheumatic drug combinations showed they reduce synovitis and erosive damage, especially when used with steroids. The subsequent sequence of disease-modifying antirheumatic drugs and the value of changing disease-modifying antirheumatic drug monotherapies or stepping-up to combination disease-modifying antirheumatic drugs are, however, unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic drugs have been evaluated, including infections and lung disease; patient-related risks seem more important than drug-related risks, though several disease-modifying antirheumatic drugs increase both types of adverse reactions. Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are reduced impact on comorbidities like cardiovascular disease and reduced patient and clinician preferences for these treatments. Nonmethotrexate disease-modifying antirheumatic drugs are effective, relatively well tolerated and widely used. Their role in intensive treatment strategies in early rheumatoid arthritis appears of crucial importance.

Cancer incidence in patients with schizophrenia and their first‐degree relatives – a meta‐analysis

Controversy concerning cancer incidence in schizophrenia exists because of heterogeneous study findings. A meta-analysis was performed on standardized incidence ratios (SIR) of cancer in patients with schizophrenia and first-degree relatives and compared with general population samples. The pooled overall cancer incidence in patients was not significantly increased (SIR = 1.05, CI 0.95-1.15). Lung cancer incidence was slightly increased (SIR = 1.31, CI 1.01-1.71), but was reduced after adjusting for smoking prevalence. The incidence of several cancers unrelated to smoking was reduced in patients. Breast cancer rates were significantly increased in female patients. The pooled overall cancer incidence in siblings (SIR = 0.89, CI 0.84-0.94) and parents (SIR = 0.90, CI 0.88-0.93) was significantly reduced. A meta-regression detected a significant relationship between cancer risk in the general population and relative risk in patients. The meta-analysis aided exploration of inconsistent study findings. There is a discrepancy between cancer risk exposure and cancer incidence in schizophrenia consistent with a protective effect.

Prognostic Value of Exercise Tolerance Testing in Asymptomatic Chronic Nonischemic Mitral Regurgitation

In many heart diseases, exercise tolerance testing (ETT) has useful functional correlates and/or prognostic value. However, its predictive value in mitral regurgitation (MR) is undefined. To determine whether ETT descriptors predict death or indications for mitral valve surgery in patients with MR, we prospectively followed, for 7 +/- 3 end-point-free years, a cohort of 38 patients with chronic severe nonischemic MR who underwent modified Bruce ETT; all lacked surgical indications at study entry. Their baseline exercise descriptors were also compared with those from 46 patients with severe MR who, at entry, already had reached surgical indications. End points during follow-up in the cohort included sudden death (n = 1), heart failure symptoms (n = 2), atrial fibrillation (n = 4), left ventricular (LV) ejection fraction <60% (n = 2), LV systolic dimensions > or =45 mm (n = 12) and >40 mm (n = 11), LV ejection fraction <60% plus LV systolic dimensions > or =45 mm (n = 3), and heart failure plus LV systolic dimensions > or =45 mm plus LV ejection fraction <60% (n = 1). In univariate analysis, exercise duration (p = 0.004), chronotropic response (p = 0.007), percent predicted peak heart rate (p = 0.01), and heart rate recovery (p <0.02) predicted events; in multivariate analysis, only exercise duration was predictive (p <0.02). Average annual event risk was fivefold lower (4.62%) with an exercise duration > or =15 versus <15 minutes (average annual risk 23.48%, p = 0.004). Relative risks in patients with and without exercise-inducible ST-segment depression were comparable (< or =1.3, p = NS) whether defined at entry and/or during follow-up. Exercise duration, but not prevalence of exercise-inducible ST-segment depression, was lower (p <0.001) in patients with surgical indications at entry versus initially end-point-free patients. In conclusion, in asymptomatic patients with chronic severe nonischemic MR and no objective criteria for operation, progression to surgical indications generally is rapid. However, those with excellent exercise tolerance have a relatively benign course. Exercise-inducible ST-segment depression has no prognostic value in this population.