Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies.

This meta-analysis describes the incidence rate of arterial and venous thromboembolism (ATE and VTE) in patients with immune thrombocytopenia (ITP), and the relative risk of ATE and VTE in patients with ITP and comparable populations without ITP. MEDLINE and EMBASE were systematically searched for observational studies reporting incidence rates of ATE and VTE in populations with and without ITP between 1996 and 2013 [follow-up completed before thrombopoietin receptor (TPOr) agonists were commercially available]. Three large, population-based studies were identified from Denmark, the United Kingdom, and the United States. The incidence of ATE per 100 patient-years among patients with ITP ranged from 1.0 to 2.8, and among populations without ITP ranged from 0.7 to 1.8; the summary relative risk adjusted for matching factors (aRR) was 1.5 [95 % confidence interval (CI) 1.3, 1.8]. The incidence of VTE per 100 patient-years among patients with ITP ranged from 0.4 to 0.7, and among populations without ITP ranged from 0.1 to 0.4; the summary aRR (95 % CI) was 1.9 (1.4, 2.7). The risk of ATE and VTE among patients with ITP, based on evidence from three large, population-based observational studies, should be considered when evaluating the risk of thromboembolism attributed to ITP treatments, such as TPOr agonists.

Racial and Ethnic Variability in the Prevalence and Incidence of Comorbidities Associated with Gastric Cancer in the United States.

PURPOSE: Comorbidities are known to impact quality of life, treatment choices, and survival. Our objectives were to characterize comorbid conditions in a cohort of elderly gastric cancer patients and to determine if there is variability in the prevalence or incidence of the comorbid conditions across racial/ethnic groups. METHODS: A total of 12,612 individuals, ≥66 years of age, diagnosed with gastric cancer between 2000 and 2007, and an equal number of gender- and region-matched cancer-free individuals, were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results registry linked to Medicare claims in the United States. The prevalence (%) in the year before diagnosis and the 12-month incidence rates after diagnosis were estimated for 32 chronic and ten acute comorbid conditions for the entire cohort and by race/ethnicity (Asian, Black, Hispanic, White, and other) and Asian subgroups (e.g., Chinese, Filipino, Japanese, Pacific Islander). RESULTS: White and Black cases exhibited the highest prevalence of most comorbid conditions. Asian and Pacific Islander cases exhibited the lowest. There was substantial variability in the 12-month incidence of the comorbidities across the racial/ethnic groups. Electrolyte disorder was the most common incident condition among Whites and Blacks. With the exception of Whites, anemia was the most common incident condition in all racial and ethnic groups 180 days following chemotherapy. CONCLUSIONS: There is variability in the prevalence and incidence in comorbidities across racial/ethnic groups.

Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle.

Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle. This case-control study used administrative claims from adult patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who received chemotherapy between 2007 and 2012. Each patient who developed febrile neutropenia (case) was matched with up to four patients without febrile neutropenia (controls) by cancer type, metastasis, chemotherapy regimen, age group, and sex. For each comorbidity (identified in the year before chemotherapy began), the adjusted odds ratio (aOR) for febrile neutropenia by cancer type was evaluated using conditional logistic regression models adjusted for potential confounding factors. Of 31,331 eligible patients, 672 developed febrile neutropenia in the first chemotherapy cycle. A total of 3312 febrile neutropenia cases and matched controls were analyzed. Across tumor types, comorbidity prevalence was higher in patients who developed febrile neutropenia than in those without febrile neutropenia. Among patients with breast cancer, osteoarthritis was more prevalent in patients with febrile neutropenia (aOR, 1.85; 95% CI, 1.07 to 3.18). Among patients with non-Hodgkin lymphoma, renal disease was more prevalent in patients with febrile neutropenia (aOR, 2.25; 95% CI, 1.23 to 4.11). Patients who developed febrile neutropenia in the first chemotherapy cycle presented with comorbidities more often than otherwise similar patients who did not develop febrile neutropenia. These findings warrant further investigation and support the inclusion of comorbidities into febrile neutropenia risk models.

Cancer chemotherapy treatment patterns and febrile neutropenia in the US Veterans Health Administration.

BACKGROUND: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States and a major cancer care provider. OBJECTIVE: To use VHA database to conduct a population-based study of patterns of myelosuppressive chemotherapy use and to assess the incidence and management of febrile neutropenia (FN) among VHA patients with lung, colorectal, or prostate cancer or non-Hodgkin lymphoma (NHL). METHODS: Data were extracted for the initial myelosuppressive chemotherapy course for 27,899 patients who began treatment in the period 2006 to 2011. FN-related costs were defined as claims containing FN diagnosis. RESULTS: Most patients were men (98.0%); most were 65 years or older (55.8%). Patients received a mean 3.4 to 3.9 chemotherapy cycles/course (median cycle duration 34-43 days). The incidence of FN among patients with lung, colorectal, or prostate cancer or NHL was 10.2%, 4.6%, 5.4%, and 17.3%, respectively. Primary or secondary prophylactic antibiotics/colony-stimulating factors were received by 21% and 12% of patients, respectively. Antibiotics were more commonly given as primary or secondary prophylaxis for patients with lung, colorectal, and prostate cancer; colony-stimulating factors were more common for patients with NHL. Among patients with FN, those with lung cancer had the highest inpatient mortality (10%); patients with NHL had the highest costs ($24,571) and the longest hospital length of stay (15.4 days). CONCLUSIONS: VHA cancer care was generally consistent with National Comprehensive Cancer Network recommendations; however, compared with the general population, chemotherapy cycles were longer, combination chemotherapy was used less, and treatment to prevent FN was used less, differences that may be attributed to the unique VHA patient population. The impact of these practices warrants further investigation.

Use of pegfilgrastim primary prophylaxis and risk of infection, by chemotherapy cycle and regimen, among patients with breast cancer or non-Hodgkin's lymphoma.

PURPOSE: This study aims to examine granulocyte colony-stimulating factor (G-CSF) prophylaxis by cancer type, chemotherapy regimen, and cycle in a real-world setting to assess if practice conforms to clinical guidelines, which recommend G-CSF prophylaxis every cycle when a patient's risk of febrile neutropenia (FN) is 20% or greater, and to describe the incidence of FN among patients who discontinue pegfilgrastim (peg) prophylaxis. METHODS: The cohort was selected from administrative claims data and includes adults diagnosed with non-Hodgkin's lymphoma (NHL) or breast cancer (BC) who began chemotherapy 2005-2010. RESULTS: About 83.2% of the 4,470 patients with BC treated with dose-dense doxorubicin, cyclophosphamide (ddAC), 83.6% of 2,197 patients with BC treated with docetaxel, doxorubicin, cyclophosphamide (TAC), and about 55.6% of the 2,722 patients with NHL treated with cyclophosphamide, doxorubicin, vincristine, with or without prednisone for 3-week cycles (CHOP-R Q3W) received peg prophylaxis in cycle 1. Among patients on these regimens who received peg prophylaxis in cycle 1 and were still on the regimen in cycle 4, about 90% received peg prophylaxis in that cycle. Among patients with BC or NHL who discontinued G-CSF, the incidence proportion of infection or FN varied by regimen and cycle, with a range from 0 to 14%. CONCLUSIONS: Despite clinical guidelines recommending G-CSF prophylaxis with chemotherapy regimens with a high risk of FN, many NHL and BC patients do not receive FN prophylaxis in cycle 1. However, among patients who receive G-CSF in cycle 1 and remain on the regimen, the majority appear to continue prophylaxis as indicated.

Prevalence of antibiotic resistance in US hospitals.

The percentage of isolates resistant to essential antibiotics among clinically significant bacterial pathogens was evaluated using data from 80089 qualifying admissions in 19 US hospitals (2007-2010). Percentage resistant was highest for the following pathogen/antibiotic pairs: Enterococcus faecium/vancomycin (87.1% [95% CI 86.0-88.1] of 4024 isolates), Staphylococcus aureus/oxacillin-methicillin (56.8% [56.1-57.4] of 23477 isolates), S. aureus/clindamycin (39.7% [39.1-40.4] of 21133 isolates), Pseudomonas aeruginosa/fluoroquinolones (32.6% [31.8-33.5] of 10982 isolates), and Escherichia coli/fluoroquinolones (31.3% [30.8-31.8] of 30715 isolates). The percentage resistant was 3.9% (3.2-4.9) for E. faecium/daptomycin (n = 2029 isolates). While these results are consistent with those from earlier studies in many respects, the percentage of E. faecium isolates resistant to daptomycin, while still small, is higher than has been reported to date.

Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors.

BACKGROUND: Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. METHODS: Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. RESULTS: Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7-7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5-1.7); carcinoembryonic antigen level, 1.9 (1.1-3.2); extrahepatic disease, 1.9 (1.5-2.4); poor tumor grade, 1.9 (1.3-2.7); positive margin, 2.0 (1.7-2.5); >1 liver metastases, 1.6 (1.4-1.8); and >3 cm tumor diameter, 1.5 (1.3-1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. CONCLUSION: The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival.

Incidence of acute kidney injury in cancer patients: a Danish population-based cohort study.

BACKGROUND: Cancer patients may be at increased risk of acute kidney injury, but evidence is limited. METHODS: We assembled a cohort of incident cancer patients diagnosed within a population-based hospital setting in Northern Denmark (population:~1.2 million) between 1999 and 2006. Patients were followed up to five years for acute kidney injury, identified using creatinine measurements recorded in a laboratory database covering the study area. Acute kidney injury was defined according to recent consensus criteria as a 50% increase in creatinine level. We computed incidence rate, 1-year, and 5-year risks of acute kidney injury, accounting for competing risk from death. Acute kidney injury incidence was compared between cancers using a Cox regression model adjusted for important confounders. RESULTS: Among 37,267 incident cancer patients with a creatinine measurement, 9613 (25.8%) developed acute kidney injury during 77,376 person-years. The incidence was 258 (95%CI: 252-264) per 1000 person-years the first year after cancer diagnosis decreasing to 43 (95%CI: 41-44) thereafter. The 1-year risk was 17.5% (95%CI: 17.1-17.9%), and the 5-year risk was 27.0% (95%CI: 26.5-27.5%). We observed the highest 1-year risk in patients with kidney cancer [44.0% (95%CI: 40.5-47.5)], liver cancer [33.0% (95%CI: 28.2-37.8%)], or multiple myeloma [31.8% (95%CI: 27.3-36.3%)]. Similar results were observed after adjustment for confounders. Both overall and for most specific cancer sites, risks were higher among patients with distant metastases at cancer diagnosis. CONCLUSION: Acute kidney injury is a common complication in cancer patients, particularly in patients with kidney cancer, liver cancer, or multiple myeloma.

Genome-wide linkage analyses of hereditary prostate cancer families with colon cancer provide further evidence for a susceptibility locus on 15q11-q14.

The search for susceptibility loci in hereditary prostate cancer (HPC) is challenging because of locus and disease heterogeneity. One approach to reduce disease heterogeneity is to stratify families on the basis of the occurrence of multiple cancer types. This method may increase the power for detecting susceptibility loci, including those with pleiotropic effects. We have completed a genome-wide SNP linkage analysis of 96 HPC families, each of which has one or more first-degree relatives with colon cancer (CCa), and further analyzed the subset of families with two or more CCa cases (n = 27). When only a prostate cancer (PCa) phenotype was considered to be affected, we observed suggestive evidence for linkage (LOD ≥1.86) at 15q14, 18q21 and 19q13 in all families, and at 1p32 and 15q11-q14 in families with two or more CCa cases. When both the PCa and CCa phenotypes were considered affected, suggestive evidence for linkage was observed at 11q25, 15q14 and 18q21 in all families, and at 1q31, 11q14 and 15q11-14 in families with two or more CCa cases. The strongest linkage signal was identified at 15q14 when both PCa and CCa phenotypes were considered to be affected in families with two or more CCa cases (recessive HLOD = 3.88). These results provide further support for the presence of HPC susceptibility loci on chromosomes 11q14, 15q11-q14 and 19q13 and highlight loci at 1q31, 11q, 15q11-14 and 18q21 as having possible pleiotropic effects. This study shows the benefit of using a comprehensive family cancer history to create more genetically homogenous subsets of HPC families for linkage analyses.

Association of caveolin-1 and -2 genetic variants and post-treatment serum caveolin-1 with prostate cancer risk and outcomes.

BACKGROUND: Caveolin-1 (cav-1) is overexpressed by metastatic prostate cancer (PC) cells. Pre-operative serum cav-1 levels have been shown to be a prognostic marker for PC recurrence. This study evaluated the relationship between post-treatment serum cav-1 levels and single nucleotide polymorphisms (SNPs) in the cav-1 and -2 genes with risk of PC, aggressive PC, PC recurrence or death. METHODS: Two case-control studies of PC among men in Washington State were combined for this analysis. Cases (n = 1,458) were diagnosed in 1993-1996 or 2002-2005 and identified via a SEER cancer registry. Age-matched controls (n = 1,351) were identified via random digit dialing. Logistic regression was used to assess the relationship between exposures (19 haplotype-tagging SNPs from all subjects and post-treatment serum cav-1 levels from a sample of 202 cases and 226 controls) and PC risk and aggressive PC. Cox proportional hazards regression was used to assess the relationship between exposures and PC recurrence and death. RESULTS: Rs9920 in cav-1 was associated with an increased relative risk of overall PC (OR(CT + CC) = 1.37, 95% CI = 1.12, 1.68) and aggressive PC (OR(CT + CC) = 1.57, 95% CI = 1.20, 2.06), but not with PC recurrence or death. High post-treatment serum cav-1 levels were not associated with PC risk, aggressive PC, or PC-specific death, but approached a significant inverse association with PC recurrence (hazard ratio = 0.69, 95% CI = 0.47, 1.00). CONCLUSIONS: We found modest evidence for an association with a variant in the cav-1 gene and risk of overall PC and aggressive PC, which merits further study. We found no evidence that higher post-treatment serum cav-1 is associated with risk of aggressive PC or adverse PC outcomes.

Population-based study of the association of variants in mismatch repair genes with prostate cancer risk and outcomes.

BACKGROUND: Mismatch repair (MMR) gene activity may be associated with prostate cancer risk and outcomes. This study evaluated whether single nucleotide polymorphisms (SNP) in key MMR genes are related to prostate cancer outcomes. METHODS: Data from two population-based case-control studies of prostate cancer among Caucasian and African-American men residing in King County, Washington were combined for this analysis. Cases (n = 1,458) were diagnosed with prostate cancer in 1993 to 1996 or 2002 to 2005 and were identified through the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. Controls (n = 1,351) were age-matched to cases and were identified through random digit dialing. Logistic regression was used to assess the relationship between haplotype-tagging SNPs and prostate cancer risk and disease aggressiveness. Cox proportional hazards regression was used to assess the relationship between SNPs and prostate cancer recurrence and prostate cancer-specific death. RESULTS: Nineteen SNPs were evaluated in the key MMR genes: five in MLH1, 10 in MSH2, and 4 in PMS2. Among Caucasian men, one SNP in MLH1 (rs9852810) was associated with overall prostate cancer risk [odds ratio, 1.21; 95% confidence interval (95% CI), 1.02, 1.44; P = 0.03], more aggressive prostate cancer (odds ratio, 1.49; 95% CI, 1.15, 1.91; P < 0.01), and prostate cancer recurrence (hazard ratio, 1.83; 95% CI, 1.18, 2.86; P < 0.01), but not prostate cancer-specific mortality. A nonsynonymous coding SNP in MLH1, rs1799977 (I219V), was also found to be associated with more aggressive disease. These results did not remain significant after adjusting for multiple comparisons. CONCLUSION: This population-based case-control study provides evidence for a possible association with a gene variant in MLH1 in relation to the risk of overall prostate cancer, more aggressive disease, and prostate cancer recurrence, which warrants replication.

FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm.

OBJECTIVE: The objective of these 2 studies was to assess the efficacy of FL-41-tinted lenses in the treatment of benign essential blepharospasm (BEB). DESIGN: A randomized crossover study and a randomized crossover case-control study. PARTICIPANTS: The first study included 30 subjects with BEB. The second study included 26 subjects with BEB and 26 controls. METHODS: For the first study, subjects were randomized to wear either FL-41 or gray-tinted lenses for 2 weeks. After a 2-week washout period, the other lens was worn for 2 weeks. Questionnaires were completed at baseline, after the first lens, and after the second lens. In the second study, surface electromyography (EMG) was used to measure blink frequency, duration, and force while subjects read and wore FL-41, rose, or gray-tinted lenses. MAIN OUTCOME MEASURES: Questionnaires were used to assess perceptions of light sensitivity and the effect of light sensitivity on activities of daily living (ADL). EMG was used to measure blink frequency, duration, and force. RESULTS: Most participants observed improvement while wearing both FL-41 and gray-tinted lenses. FL-41-tinted lenses provided superior improvement in the areas of reading, fluorescent light sensitivity, overall light sensitivity, blepharospasm frequency, and blepharospasm severity. FL-41 lenses reduced mean blink rate compared with both rose and gray-tinted lenses, and reduced eyelid contraction force compared with rose-tinted lenses. CONCLUSIONS: FL-41 lenses provided both subjective and objective benefit to subjects with BEB. Physicians should consider recommending this noninvasive and inexpensive lens tint to patients with BEB. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A comparison of idiopathic intracranial hypertension with and without papilledema.

OBJECTIVE: To compare clinical features, visual characteristics, and treatment of idiopathic intracranial hypertension patients with and without papilledema. BACKGROUND: Idiopathic intracranial hypertension does not often occur without papilledema. This study estimates the prevalence and compares the clinical characteristics of idiopathic intracranial hypertension patients with and without papilledema. METHODS: We performed a cross-sectional analysis of all idiopathic intracranial hypertension patients diagnosed at the University of Utah Neuro-Ophthalmology Unit between 1990 and 2003. Patient records were reviewed for presence of papilledema and other signs, symptoms, and treatment characteristics. Each patient without papilledema was matched to the patient with papilledema who was closest to his/her age and sex. McNemar's and Wilcoxon-signed rank sum tests were used to compare characteristics between matched pairs. RESULTS: Among all patients (n = 353), the prevalence of those without papilledema was 5.7% (n = 20). Patients without papilledema reported photopsias (20%), and were found to have spontaneous venous pulsations (75%) and non-physiologic visual field constriction (20%) more often than did those with papilledema. Mean opening pressure, although above normal, was lower in patients without papilledema (mean = 309 mm cerebrospinal fluid) compared with those with papilledema (mean = 373 mm cerebrospinal fluid, P = .031). Idiopathic intracranial hypertension patients without papilledema had more frequent diagnostic lumbar punctures than did patients with papilledema. Visual acuities and treatment were similar between groups. CONCLUSIONS: The clinical presentation of idiopathic intracranial hypertension without papilledema is only somewhat different from that of idiopathic intracranial hypertension with papilledema. The lower opening pressure in patients without papilledema may explain variations in symptoms and signs between the 2 groups. When there are visual field changes in idiopathic intracranial hypertension without papilledema, non-physiologic visual loss should be considered.

Genetic etiology of hereditary prostate cancer.

Prostate cancer (PC) is a pervasive disease both in terms of incidence and mortality, yet little is known about its etiologic factors. Twin and segregation studies provide evidence for an inherited genetic component to the etiology of PC, yet over a dozen family-based genetic linkage analyses have not been able to consistently identify susceptibility loci. This chapter will review these studies, describe the challenges of this endeavor, and describe efforts to confront these challenges, such as using larger sets of families and more homogeneous subgroups.

Glutathione S-transferase M1, T1, and P1 polymorphisms and prostate cancer risk in middle-aged men.

BACKGROUND: The glutathione S-transferase (GST) enzymes detoxify several carcinogens. Genetic polymorphisms in GSTM1, T1, and P1 (Ile105Val) have been associated with prostate cancer, however, results have been inconsistent across studies. METHODS: Data from a population-based case-control study in King County, Washington, were used to further evaluate the relationships between these GST polymorphisms and prostate cancer. Incident cases (n = 590) were 40-64 years old, diagnosed from 1993 through 1996, and identified via the SEER cancer registry. Controls (n = 538) were identified via random digit dialing, and frequency age-matched to cases. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Risk of prostate cancer was moderately increased among Caucasians with the GSTM1-null genotype (OR = 1.54; 95% CI 1.19-2.01). There were no associations for either GSTT1 or P1(Ile105Val). The association between the GSTM1-null genotype and prostate cancer was not different according to cancer aggressiveness defined by stage at diagnosis and Gleason score. Among GSTM1-null Caucasians, the relative risk of prostate cancer increased linearly with increasing pack-years of smoking (P-value for trend = 0.007), with the highest ORs observed for smokers of >30 pack-years. CONCLUSIONS: Findings suggest that the GSTM1-null genotype defines a subgroup of men at higher risk of prostate cancer, particularly if they are heavy smokers.