Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis.

OBJECTIVE: The comparative risk of infection associated with non-anti-tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non-anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA). METHODS: Using 1998-2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic agent use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders. RESULTS: Among 3,152 unique RA patients contributing 4,158 biologic treatment episodes to rituximab (n = 596), abatacept (n = 451), and anti-TNF agents (n = 3,111), the patient mean age was 60 years and 87% were male. The most common infections were pneumonia (37%), skin/soft tissue (22%), urinary tract (9%), and bacteremia/sepsis (7%). Hospitalized infection rates per 100 person-years were 4.4 (95% CI 3.1-6.4) for rituximab, 2.8 (95% CI 1.7-4.7) for abatacept, and 3.0 (95% CI 2.5-3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 95% CI 0.9-2.2), abatacept (HR 1.1, 95% CI 0.6-2.1), or rituximab (HR 1.4, 0.8-2.6), although it was increased for infliximab (HR 2.3, 95% CI 1.3-4.0). Infection risk was greater for those taking prednisone >7.5 mg/day (HR 1.8, 95% CI 1.3-2.7) and in the highest quartile of C-reactive protein (HR 2.3, 95% CI 1.4-3.8) and erythrocyte sedimentation rate (HR 4.1, 95% CI 2.3-7.2) compared to the lowest quartile. CONCLUSION: In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.

Incidence of progressive multifocal leukoencephalopathy in patients without HIV.

OBJECTIVE: To estimate the incidence rate (IR) of progressive multifocal leukoencephalopathy (PML) in patients without HIV. METHODS: Within a large US health insurer database between January 2000 and June 2008, we conducted a retrospective observational study. We identified people with autoimmune diseases, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), or history of bone marrow or solid organ transplantation, and a general population cohort. We developed a PML case-finding algorithm and validated PML diagnoses in medical charts. RESULTS: There were 138,469 patients with autoimmune diseases, 25,706 with NHL or CLL, and 8,778 with transplants. Among 699 people who met screening criteria for potential PML, 89 had a claim diagnosis of PML (International Classification of Diseases-9 046.3). Medical records were sought for 24 patients without HIV, and 6 had confirmed PML upon review of medical records. The PML IR was 2.4 (95% confidence interval [CI] 0.06-13.18) in the systemic lupus erythematosus cohort and 10.8 (95% CI 0.27-60.39) in the autoimmune vasculitis cohort per 100,000 person-years. In the NHL and CLL cohorts, the IR was 8.3 (95% CI 1.71-24.24) and 11.1 (0.28-61.74) per 100,000 person-years. The IR among patients with bone marrow transplantation was 35.4 per 100,000 person-years (95% CI 0.90-197.29). There were no cases of PML among patients with rheumatoid arthritis (95% CI 0.0-2.24), multiple sclerosis (95% CI 0.0-5.24), Sjögren disease (95% CI 0.0-21.84), or solid organ transplantation (95% CI 0.0-26.81). CONCLUSIONS: In this large population-based investigation of PML with thorough case finding and a known source population, the IR of medical record-confirmed PML was rare in non-HIV patient cohorts.

Population-based study on incidence, risk factors, clinical complications and drug utilisation associated with influenza in the United Kingdom.

This large population-based study using the UK-based General Practice Research Database was conducted to quantify influenza-related physician visits, clinical complications of and risk factors for influenza, and related drug use in all age groups from 1991 to 1996. A total of 141,293 subjects who had one or more diagnoses of influenza or influenza-like illness during the study period as well as the same number of age-, sex-, practice and calendar time-matched controls were identified. Adults aged 15-64 years had the highest influenza incidence rate. The risk of getting influenza was particularly increased for subjects with chronic respiratory conditions (asthma or chronic obstructive pulmonary disease, odds ratio 1.65, 95% confidence interval 1.60-1.70). Subjects with influenza were more likely to have a diagnosis of clinical complications than control subjects (relative risk 3.4, 95% confidence interval 3.3-3.6). The risk of developing clinical complications was highest for children and was elevated for subjects with certain underlying chronic conditions. In absolute terms, otherwise healthy adults (15-64 years) accounted for the greatest proportion of all influenza-related physician visits as well as clinical complications in this study population. Of the 141,293 subjects with influenza, 83,911 (59.4%) received drugs on prescription. The most frequently prescribed drugs were antibiotics (45.2%), followed by antipyretics/analgesics (22.5%). Influenza patients were approximately six times more likely to use drugs on prescription than controls. This analysis may lead to further analyses on the economic impact of influenza and the contribution of different population groups to that burden.

Microvascular invasion of the seminal vesicles in adenocarcinoma of the prostate.

The objective of this article is to determine the relationship between microvascular invasion and seminal vesicle invasion in prostatic adenocarcinoma. Radical prostatectomies with seminal vesicle involvement were examined histologically and immunohistochemically with antibodies directed against S-100 protein and factor VIII. Microvascular invasion of the seminal vesicles showed a positive correlation with microvascular and capsular invasion of the prostate (P = 0.006 and 0.048, respectively) and lymph node metastases. Tumor progression was found in 8 of 14 (57%) patients with microvascular invasion of the seminal vesicles, compared with 3 of 22 (14%) without microvascular invasion (P = 0.001). Microvascular invasion of the seminal vesicles is predictive of tumor progression and lymph node metastases in prostatic adenocarcinoma.

Incidence of prostate cancer will double by the year 2030: the argument for.

Prostate cancer is a frequent cancer in old men which increases with age and is associated with wide geographical variation. Even if age-specific incidence rates remain stable, the problem of prostate cancer seems certain to increase in absolute terms simply because of the ageing of the population. This will have major economic implications for the future, particularly in Westernised societies, with any temporal trend in risk serving only to further compound the problem. However, since the risk of dying from prostate cancer has remained unchanged in many countries throughout this century, it may be that the increased incidence may be the result of increasing transurethral resection of the prostate procedures or screening techniques which have increased the detection and reporting of prostate cancer.

Worldwide patterns of prevalence and mortality from benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) can be found in 88% of autopsies in men > or = 80 years, with compatible symptomatology reported in nearly 50% of men aged > or = 50 years in the general population. Despite such a common occurrence, little is known with any certainty about the epidemiology of BPH (for which "prostatism" is a commonly, and wrongly, used synonym). Knowledge of risk factors is sparse: analytic epidemiologic studies of BPH are difficult to conduct. It is essential to establish an epidemiologic definition of BPH for these reasons. Both BPH and prostatism are the problems that seem set to increase in absolute terms. They are clearly identified as priority areas for research into their causes and treatment. However, it is clear that there is a great need for more epidemiologic information, particularly regarding prostatism, whose occurrence is unknown in many parts of the world.

Geographical and temporal patterns of incidence and mortality from prostate cancer.

In many countries of the world, prostate cancer is the second most common form of cancer in men, and in the United States it is now in first rank. It is an important public health problem, with > 0.25 million new cases diagnosed worldwide in the year 1985. Whereas earlier large increases in the incidence of prostate cancer were apparent throughout the world, the mortality rate has remained constant in generations of men born since the early years of this century. Most importantly, given that in several countries the increased number of children born after World War II will be in their mid-50s in the early part of the 21st century (at an age when cancer risk is becoming an important consideration), and coupled with the trends in increasing life expectancy, the consequence will be an increase in absolute terms in the number of cases of prostate cancer diagnosed. In the absence of treatment improvements and with prospects for prevention by modification of lifestyle remote within current knowledge, there will also be an increase in the number of deaths from prostate cancer worldwide. The situation would be further augmented by the presence of a temporal trend in risk that is widely reported from many countries and unlikely to be entirely artefact.

Intravesical suramin in the prevention of transitional cell carcinoma.

OBJECTIVES: To examine the effects of intravesical suramin on N-methyl-N-nitrosurea (MNU)-induced bladder tumors in Fischer 344 rats. METHODS: Multiple cohorts of female rats received four biweekly intravesical instillations of MNU. A control group received no other treatment, the experimental group received 25 mg/kg intravesical suramin twice a week beginning at week 6. RESULTS: After 18 weeks from the first instillation of MNU, 60% to 65% of control animals developed papillary transitional cell carcinoma, compared with only 0% to 10% of the suramin-treated animals (P = 0.01 to P = 0.0007). There was no local or systemic toxicity observed. CONCLUSIONS: Intravesical suramin is an effective chemopreventative therapy for transitional cell carcinoma in vivo with minimal toxicity.

The epidemiology of benign prostatic hyperplasia and observations on concomitant hypertension.

Benign prostatic hyperplasia (BPH) and hypertension are highly prevalent, age-related disorders in men which place a considerable burden on healthcare resources worldwide. Evidence of pathological BPH can be found in over 80% of autopsies conducted in men over 70 years of age; around 40% of men aged 50-64 years have symptoms compatible with the disease. Population studies suggest that over 50% of people aged 65-74 years may be hypertensive, and that cardiovascular disease is a major cause of death worldwide. The continued ageing of the population means that more people are living to older ages; life expectancy for men is likely to exceed 80 years by the end of this century in some developed countries. While BPH and hypertension are apparently diverse disease processes, they have some features in common (e.g. underlying aetiology of the sympathetic nervous system). However, little else is known about any associations between the two or the frequency of concomitant disease. There are clearly opportunities for further epidemiologic studies and the development of preventive strategies aimed at the early detection and treatment of concomitant BPH and hypertension.

Staging of early prostate cancer: a proposed tumor volume-based prognostic index.

Current staging of early prostate cancer separates patients into two groups: those with palpable and non-palpable tumors. Such staging relies on digital rectal examination in making this separation, despite the low sensitivity, low specificity, and low positive predictive value of this method. As an alternative, tumor volume may be useful for staging because of its powerful prognostic ability and its potential to be assessed clinically due to recent advances in imaging techniques such as transrectal ultrasound. In this study, we evaluate the utility of tumor volume in predicting progression of early prostate cancer based on the composite published evidence from nine pathologic studies of serially-sectioned prostates. Logistic regression revealed that tumor volume was a good positive predictor of all measures of tumor progression. There was a 10 percent probability of capsular invasion in tumors measuring about 0.5 cm3; 10 percent probability of seminal vesicle invasion in tumors measuring about 4.0 cm3; and 10 percent probability of metastases in tumors measuring about 5.0 cm3. These composite results suggest that tumor volume is a significant predictor of cancer progression. A volume-based prognostic index is proposed as an adjunct to staging for early prostate cancer.

[Diagnostic potential of indirect radionuclide angiography in kidney cancer]. / Diagnosticheskie vozmozhnosti nepriamoi radionuklidnoi angiografii pri rake pochki.

Indirect radionuclide angiography was performed in 95 suspects for renal tumor. The data obtained by the said procedure were compared to those yielded by surgery, autopsy and X-ray contrast angiography. The majority of renal tumors were found to have specific angionephroscintigraphic features. The sensitivity of the method in detecting renal carcinoma was 90.2%, specificity--86.3 and diagnostic reliability--88.4%. The procedure proved functional, sparing and highly informative.

[Reasons for relaparotomies following operations on the biliary tract in nontumorous lesions]. / Prichiny relaparotomii posle operatsii na zhelchnykh putiakh pri ikh neopukholevykh porazheniiakh.

According to the authors' data the incidence of relaparotomies after 1500 operations for non-tumor diseases of bile ducts was 2.5%. Causes of relaparotomies at early and late terms of the postoperative period were different. The dependence of results of the treatment on the amount of relaparotomies and the presence of such complications as jaundice, cholangitis and pancreatitis has been established. In such complications and increased amount of relaparotomies lethality was considerably higher. General lethality after relaparotomies was 49%. Complex of prophylactic and curative measures of the complications resulting in relaparotomies has been developed.

[Indications for surgery in acute and chronic hepatitis]. / Pokazaniia k operatsii pri ostrom i khronicheskom gepatite.

The author considers that the participation of surgeons in the treatment of patients with acute and chronic hepatitis may be promising. The operation for acute hepatitis is aimed at liquidation of another disease of the patients, that for chronic hepatitic is fulfilled in order to relieve severe manifestations of the disease.

[Surgical tactics in chronic non-calculous cholecystitis]. / Khirurgicheskaia taktika pri khronicheskom beskamennom kholetsistite.

The authors have an experience with 1500 operations on bile ducts in patients with non-tumorous diseases. The operative treatment of acalculous cholecystitis was indicated only in isolated cases. After an insufficiently grounded cholecystectomy symptoms of the disease not only persisted but also made progress and new ones appeared resulting from the operation. Patients with acalculous cholecystitis must be subjected to a comprehensive examination at a specialized gastroenterological departments.