Untreated HIV infection is associated with endothelial dysfunction and subsequent cardiovascular disease, likely due to both direct effects of the virus and to indirect effects of systemic inflammation on the vasculature. We have recently shown that treatment with the antiinflammatory agent pentoxifylline (PTX) improved in vivo endothelial function and reduced circulating levels of the inflammatory markers vascular cell adhesion molecule-1 (VCAM-1) and interferon-gamma-induced protein (IP-10) in HIV-infected patients. To delineate the mechanisms underlying this therapeutic effect, we tested whether clinically relevant concentrations of PTX suppress VCAM-1 or IP-10 release in cultivated human lung microvascular endothelial cells. Indeed, we found that tumor necrosis factor (TNF)-α-induced VCAM-1 was reduced with concentrations of PTX in the low nanomolar range, comparable to plasma levels in PTX-treated groups. We also investigated the effect of HIV proteins and found that HIV transactivator of transcription (HIV-Tat) and HIV-envelope-derived recombinant gp120 enhanced TNF-α-induced VCAM-1 gene expression in lung microvascular and coronary macrovascular endothelial cells, respectively. In addition, PTX and a NF-κB-specific inhibitor reduced this enhanced VCAM-1 gene induction in microvascular and macrovascular endothelial cells. These results provide novel insights in how the antiinflammatory agent PTX can directly reduce HIV-associated proinflammatory endothelial activation, which may underlie vascular dysfunction and coronary vascular diseases.
Hepatocellular carcinoma (HCC) surveillance is underutilized among patients with cirrhosis. Understanding which steps in the surveillance process are not being performed is essential for designing effective interventions to improve surveillance rates. Our study's aim was to characterize reasons for failure in the HCC surveillance process among a cohort of cirrhotic patients with HCC. We conducted a retrospective cohort study of cirrhotic patients diagnosed with HCC at a large urban safety-net hospital between 2005–2011. Patients were characterized by receipt of HCC surveillance over a two-year period prior to HCC diagnosis. Among patients without HCC surveillance, we classified reasons for failure into four categories: failure to recognize liver disease, failure to recognize cirrhosis, failure to order surveillance, and failure to complete surveillance despite orders. Univariate and multivariate analyses were performed to identify predictors of failures. We identified 178 patients with HCC, of whom 20% had undergone surveillance. There were multiple points of failure- 20% had unrecognized liver disease, 19% had unrecognized cirrhosis, 38% lacked surveillance orders, and 3% failed to complete surveillance despite orders. Surveillance was more likely among patients seen by hepatologists (OR 6.11, 95%CI 2.5–14.8) and less likely in those with alcohol abuse (OR 0.14, 95%CI 0.03–0.65). Although a retrospective analysis in a safety-net hospital, our data suggest only one in five patients received surveillance prior to HCC diagnosis. There are multiple points of failure in the surveillance process, with the most common being failure to order surveillance in patients with known cirrhosis. Future interventions must target multiple failure points in the surveillance process to be highly effective.
Screening; underutilization; quality of care; liver cancer; cirrhosis
BACKGROUND & AIMS
Colorectal cancer (CRC) screening with colonoscopy often requires expensive copayments from patients. The 2010 Patient Protection and Affordable Care Act mandated elimination of copayments for CRC screening, including colonoscopy, but little is known about the effects of copayment elimination on use. The University of Texas employee, retiree, and dependent health plan instituted and promoted a waiver of copayments for screening colonoscopies in fiscal year (FY) 2009; we examined the effects of removing cost sharing on colonoscopy use.
We conducted a retrospective cohort study of 59,855 beneficiaries of the University of Texas employee, retiree, and dependent health plan, associated with 16 University of Texas health and nonhealth campuses, ages 50 – 64 years at any point in FYs 2002–2009 (267,191 person-years of follow-up evaluation). The primary outcome was colonoscopy incidence among individuals with no prior colonoscopy. We compared the age- and sex-standardized incidence ratios for colonoscopy in FY 2009 (after the copayment waiver) with the expected incidence for FY 2009, based on secular trends from years before the waiver.
The annual incidence of colonoscopy increased to 9.5% after the copayment was waived, compared with an expected incidence of 8.0% (standardized incidence ratio, 1.18; 95% confidence interval, 1.14 –1.23; P < .001). After adjusting for age, sex, and beneficiary status, the copayment waiver remained significantly associated with greater use of colonoscopy, with an adjusted hazard ratio of 1.19 (95% confidence interval, 1.12–1.26).
Waiving copayments for colonoscopy screening results in a statistically significant, but modest (1.5%), increase in use. Additional strategies beyond removing financial disincentives are needed to increase use of CRC screening.
Colorectal Neoplasm; Cost Sharing; Early Detection; Colon Cancer
Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.
We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD) of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD) and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed.
The difference in mean absolute change (SD) in FMD after 8 weeks between the placebo [−1.06 (1.45)%] and PTX [−1.93 (3.03)%] groups was not significant (P = 0.44). No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI) [−83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated.
PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.
The current therapy for patients hospitalized with ascites requires titration of oral diuretics and often needs several days. A faster method for predicting the response to a given dose of diuretic may allow this process to be completed more rapidly.
Describe the short-term safety and efficacy of a diuretic infusion to predict net sodium excretion in patients with cirrhosis, ascites and edema using a fractional excretion of sodium (FENa) of ≥1% as the target.
We conducted a retrospective case series of patients admitted for management of ascites who received intravenous furosemide by continuous infusion in ascites management. Patients were stratified depending on whether they had edema, received an intravenous bolus of furosemide or a large-volume paracentesis. The primary outcome was the proportion of patients achieving a FENa of ≥1% during the infusion. Secondary outcomes included development of electrolyte abnormalities or acute kidney injury (AKI) during or immediately following the infusion and natriuresis on titrated oral furosemide.
47 patients meeting criteria were identified from 721 patients seen in consultation. 10 of the patients had edema and received neither bolus intravenous diuretic therapy nor therapeutic paracentesis; all ten achieved a FENa ≥1%. One patient had transient hypokalemia. Of 37 patients who either had no edema or received additional treatment options, all but six patients achieved a FENa of ≥1%. Transient complications in the 31/37 patients with natriuresis included hyponatremia (n = 1), hypokalemia (n = 5) and AKI (n = 3). 24 hour urine sodium averaged > 4 g/d on the titrated oral furosemide regimen in 19 patients completing the collection.
Use of a short continuous furosemide infusion can achieve a FENa ≥ 1% in patients with cirrhotic ascites and may be safe and efficacious for diuresis, meriting further study.
To examine the association between changes in glomerular filtration rates (GFR) and antiretroviral therapy (ART)-mediated suppression of plasma HIV-1 viremia.
Observational, prospective, multicenter cohort study.
ART regimens or treatment strategies in HIV-1-infected subjects were implemented through randomized clinical trials; 1776 ambulatory subjects from these trials also enrolled in this cohort study.
The association between suppression of viremia and GFR changes from baseline was examined using the abbreviated Modification of Diet and Renal Disease equation in mixed effects linear models.
GFR improvement was associated with ART-mediated suppression of plasma viremia in subjects with both chronic kidney disease stage ≥2 and low baseline CD4 cell counts (< 200 cells/µl). In this subset, viral suppression (by > 1.0 log10 copies/ml or to < 400 copies/ml) was associated with an average increase in GFR of 9.2 ml/min per 1.73 m2 from baseline (95% confidence interval, 1.6–16.8; P = 0.02) over a median follow-up of 160 weeks. The magnitude of this association increased in subjects who had greater baseline impairment of renal function, and it did not depend on race or sex.
Viral suppression was associated with GFR improvements in those with both low CD4 cell counts and impaired baseline renal function, supporting an independent contribution of HIV-1 replication to chronic renal dysfunction in advanced HIV disease. GFR improvement not associated with viral suppression also was observed in subjects with higher CD4 cell counts.
antiretroviral therapy; chronic kidney disease; HIV-1 viremia; HIV-associated nephropathy
It is unknown whether systemic endothelial dysfunction underlies the association between nephropathy and cardiovascular disease (CVD) in persons infected with human immunodeficiency virus (HIV). Spot urine protein to creatinine ratio, spot urine albumin to creatinine ratio, creatinine clearance, estimated glomerular filtration rate, and flow-mediated dilation (FMD) of the brachial artery were evaluated in 123 study participants infected with HIV (58 receiving antiretroviral therapy [ART] and 65 not receiving ART) with no history of diabetes or hypertension. None of the renal markers, modeled as either continuous or categorical variables, correlated with FMD. Contrary to expectations, endothelial dysfunction may not be the link between nephropathy and CVD in HIV.
Surfactant replacement therapy has been the mainstay of treatment for preterm infants with respiratory distress syndrome for more than twenty years. For the most part, surfactant is administered intratracheally, followed by mechanical ventilation. In recent years, the growing interest in noninvasive ventilation has led to novel approaches of administration. This paper will review these techniques and the associated clinical evidence.
We assessed metabolic changes for darunavir/ritonavir (DRV/r) once daily (qd) versus atazanavir/ritonavir (ATV/r) qd with fixed-dose tenofovir/emtricitabine. This was a phase 4, multicenter, open-label, randomized exploratory study. Treatment-naive, HIV-1-infected adults received DRV/r 800/100 mg qd or ATV/r 300/100 mg qd, both with emtricitabine/tenofovir 200/300 mg qd. Primary end point: change in triglyceride levels from baseline to week 12. Secondary end points: week 12 and week 48 changes in lipid parameters, insulin sensitivity, inflammatory/coagulation/bacterial translocation biomarkers, viral load, CD4+ cell count, and week 48 changes in adipose tissue distribution and subjects' perceptions of body changes. In the DRV/r arm, 32/34 and 29/34 subjects completed weeks 12 and 48, respectively; in the ATV/r arm, 30/31 and 25/31 subjects completed weeks 12 and 48, respectively. Small changes in lipid parameters from baseline to weeks 12 and 48 were observed in both arms. Differences were noted between arms in mean changes in total cholesterol (DRV/r, 20.3 mg/dl; ATV/r, 4.6 mg/dl) and apolipoprotein A1 (DRV/r, 10.7 mg/dl; ATV/r, –0.7 mg/dl) at week 12. At week 48, no clinically relevant differences between arms were noted for changes in any lipid parameter, fasting glucose, or insulin sensitivity. Biomarkers generally decreased and efficacy parameters improved in both arms over 48 weeks. Changes in adipose tissue were small and comparable between arms. Subjects' perceptions of body changes generally improved in both study arms. This first pilot comparison in HIV-1-infected subjects suggests that DRV/r has a metabolic profile similar to ATV/r over 48 weeks of treatment. Further randomized studies are warranted.
Changes in endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, has not been systematically assessed beyond 6 months of initiation of antiretroviral therapy (ART) when drug-related effects might offset initial improvements with virologic control.
We assessed 6 and 12 month changes in FMD [presented as median (quartile 1, quartile 3)] and circulating HIV and cardiovascular biomarkers in 23 subjects initiating ART.
There were no significant changes in FMD at 6 or 12 months overall despite significant increases in CD4 cell count and HDL-C and reductions in HIV RNA level, MCP-1, IP-10, sVCAM-1, sTNFR2, and sCD14. However, there were significant differences (P = 0.04) in the changes in FMD between those receiving efavirenz [N = 12; −3.50% (−4.90%, 0.68%)] vs. protease inhibitors at 12 months [N = 11; 1.50% (−0.86%, 4.56%)]. The differences in changes in FMD between those receiving and not receiving emtricitabine/tenofovir/efavirenz were more pronounced and were significantly different at both 6 and 12 months (P<0.02 for both). Additional studies showed no significant differences in changes in 25-(OH)-vitamin D, PTH, FGF-23, of F2-isoprostane levels between efavirenz and PI use or between those receiving and not receiving emtricitabine/tenofovir/efavirenz.
Efavirenz use was associated with reduced FMD at 12 months compared to PI-based regimens while emtricitabine/tenofovir/efavirenz was associated with reduced FMD at both 6 and 12 months compared to those not receiving this combination. Long-term effects of antiretrovirals on endothelial function may play an important role in the risk of cardiovascular disease in HIV-infected patients.
Circulating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings.
We examined data from a cross-sectional single site study at Indiana University (Indiana, N = 85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N = 75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm3 (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm3 at entry which increased to 396 cells/mm3 on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely correlated with FMD (r = −0.33, p = 0.02), but not sCD14 (r = −0.01, p = 0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (p = 0.02).
In HIV- infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.
The innate proatherosclerotic properties of non-nucleoside reverse transcriptase inhibitors have not previously been examined. Therefore, we performed a pilot study of etravirine (ETR) in healthy volunteers over 28 days. This investigation also allowed us to evaluate the safety of ETR over a period commonly used for HIV postexposure prophylaxis. ETR 200 mg twice daily was given to 28 healthy HIV-uninfected volunteers over 28 days. Flow-mediated dilation (FMD) of the brachial artery and circulating markers of inflammation, coagulation, and metabolism were measured at entry and at day 28. These circulating markers were also measured at day 35. Of the initial 28 subjects, 23 completed both entry and day 28 procedures. Two subjects were discontinued due to development of rash. No other major toxicities developed. The change in FMD over 28 days was minimal and not significant (0.03 [−3.21, 0.97] %; p=0.36). The post hoc estimated detectable absolute change in FMD with the 23 subjects in our study was 2.26%, which is an effect size that has been associated with future cardiovascular event rates in the general population; thus our study had sufficient power to find clinically relevant changes in FMD. In addition, there were no significant changes in any of the circulating markers from entry to day 28 or from day 28 to day 35. ETR did not demonstrate any innate proatherosclerotic properties over 28 days in these HIV-uninfected volunteers. ETR was generally well tolerated. Larger studies are warranted to confirm that ETR can be used safely as part of HIV postexposure prophylaxis regimens.
Active patient and public involvement as partners in their own health care and in the development of health services is key to achieving a health care system that is responsive to patients’ needs and values. It promotes better use of the health care system, and improves health outcomes, quality of life and patient satisfaction. By involving patients and health care professionals as partners in the creation and updating of patient health support tools, wikis—highly accessible, interactive vehicles of communication—have the potential to empower users to implement these support tools in daily life.
Acknowledging the potential of wikis, and recognizing that they capitalize on the free and open access to information, scientists, opinion leaders and patient advocates have suggested that wikis could help decision-making constituencies improve the delivery of health care. They might also decrease its cost and improve access to knowledge within developing countries. However, little is known about the efficacy of wikis in helping to attain these goals. There is also a need to know more about the intention of patients and health care workers to use wikis, in what circumstances and what factors will influence their use of wikis.
In this issue of the Journal of Medical Internet Research, Gupta et al describe how they developed and tested a new wiki-inspired application to improve asthma care. The researchers involved patients with asthma, primary care physicians, pulmonologists and certified asthma educators in the construction of an asthma action plan. Their paper—entitled “WikiBuild: a new online collaboration process for multistakeholder tool development and consensus building”—is the first description of a wiki-inspired technology built to involve patients and health care professionals in the development of a patient support tool. This innovative study has made important contributions toward how wikis could be generalized to involve multiple stakeholders in the development of other knowledge translation tools such as clinical practice guidelines or decision aids. More specifically, Gupta et al have uncovered potential action mechanisms toward increasing usage of these tools by patients and health care professionals. These are decreasing hierarchical influences, increasing usability and adapting a tool to local context.
More research is now needed to determine if the use of the resulting wiki-developed plan will actually be higher than a plan developed using other methods. Furthermore, there is also a need to assess the intention of participants to continue using wiki-based processes on an ongoing basis. It is in this dynamic and continuous retroaction loop that the support tool users—both patients and health care professionals—can adapt and improve the product after its real-life shortcomings are revealed and as new evidence becomes available. As such, a wiki would be more than a simple patient support development tool, but could also become a dynamic and interactive repository and delivery tool that would facilitate ongoing and sustainable patient and professional engagement.
Medical informatics; patient-centered care; wikis; collaborative writing applications; knowledge translation; patient and public involvement
Production of media such as patient education tools requires methods that can integrate multiple stakeholder perspectives. Existing consensus techniques are poorly suited to design of visual media, can be expensive and logistically demanding, and are subject to caveats arising from group dynamics such as participant hierarchies.
Our objective was to develop a method that enables multistakeholder tool building while averting these difficulties.
We developed a wiki-inspired method and tested this through the collaborative design of an asthma action plan (AAP). In the development stage, we developed the Web-based tool by (1) establishing AAP content and format options, (2) building a Web-based application capable of representing each content and format permutation, (3) testing this tool among stakeholders, and (4) revising this tool based on stakeholder feedback. In the wiki stage, groups of participants used the revised tool in three separate 1-week “wiki” periods during which each group collaboratively authored an AAP by making multiple online selections.
In the development stage, we recruited 16 participants (9/16 male) (4 pulmonologists, 4 primary care physicians, 3 certified asthma educators, and 5 patients) for system testing. The mean System Usability Scale (SUS) score for the tool used in testing was 72.2 (SD 10.2). In the wiki stage, we recruited 41 participants (15/41 male) (9 pulmonologists, 6 primary care physicians, 5 certified asthma educators, and 21 patients) from diverse locations. The mean SUS score for the revised tool was 75.9 (SD 19.6). Users made 872, 466, and 599 successful changes to the AAP in weeks 1, 2, and 3, respectively. The site was used actively for a mean of 32.0 hours per week, of which 3.1 hours per week (9.7%) constituted synchronous multiuser use (2–4 users at the same time). Participants averaged 23 (SD 33) minutes of login time and made 7.7 (SD 15) changes to the AAP per day. Among participants, 28/35 (80%) were satisfied with the final AAP, and only 3/34 (9%) perceived interstakeholder group hierarchies.
Use of a wiki-inspired method allowed for effective collaborative design of content and format aspects of an AAP while minimizing logistical requirements, maximizing geographical representation, and mitigating hierarchical group dynamics. Our method faced unique software and hardware challenges, and raises certain questions regarding its effect on group functioning. Potential uses of our method are broad, and further studies are required.
Consensus; focus groups; user-computer interface; Web 2.0; asthma; self-care
Though the presence of microsatellite instability (MSI) in patients with colorectal cancer (CRC) may have implications for prognosis, therapy, and family counseling, MSI prevalence is not well described among individuals of Hispanic origin in the United States (US) with CRC.
We conducted a retrospective cohort study employing a hospital-based tumor registry to identify individuals of Hispanic origin diagnosed with CRC. Clinical data and tumor samples were retrieved. Molecular analyses included testing for MSI using a panel of 5 mononucleotide markers (BAT25, BAT26, NR21, NR24 and NR27) in a pentaplex polymerase chain reaction assay, as well as immunohistochemistry for the MMR proteins MLH1, MSH2, MSH6, and PMHS2 on representative tissue.
111 individuals of Hispanic origin with CRC were identified. 41.1% were women, median age was 57 years (IQR:47.1–63.5). 11 (9.8%, 95%CI:4.2–15.6) had MSI CRC, while 14 (14.6%, 95%CI:7.3–21.8) had CRC with≥1 MMR protein abnormality. 10 of 11 individuals with MSI had clinical or molecular characteristics suspicious for Lynch syndrome such as abnormal expression of MSH2 and/or MSH6 (n=7) or age<50 at diagnosis (n=7).
The prevalence of MSI CRC among Hispanic individuals may be similar to other races and ethnicities, but clinical-pathological characteristics, including age at diagnosis and pattern of abnormal MMR protein expression, suggests that sporadic MSI CRC may be less common in individuals of Hispanic origin, and that much MSI observed in this situation may be attributable to Lynch syndrome. Further exploration of the causes of disparate presentations of CRC by ethnicity and race is warranted.
colorectal neoplasms; Hispanic Americans; genomic instability; microsatellite instability; DNA mismatch repair
Vascular endothelial dysfunction may contribute to the increase in cardiovascular events during HIV-1 infection and its treatment. Antiretroviral therapy (ART), metabolic factors, lipodystrophy, and HIV infection itself may be involved. Ninety-six HIV-infected subjects were evaluated for endothelial function by measurement of brachial artery flow-mediated dilation (FMD) by ultrasound, single-slice CT of the abdomen and mid-thigh, whole-body dual x-ray absorptiomety (DXA) scans, and metabolic evaluations in a cross-sectional study. The median age was 40 years; 28% were female, 38% black, 3% Hispanic, and 59% white. Forty-nine (51%) were receiving ART, which included a PI in 28 (57%) and was non-PI based in 21 (43%). FMD (±SD) in subjects not on ART was 5.5 ± 4.3%, PI-ART 5.3 ± 3.6%, and non-PI-ART 5.5 ± 4.1% (p = 0.9). Age, race, CD4 cell count, and HIV RNA did not correlate significantly with FMD. Among ART-treated subjects in the lowest tertile of thigh subcutaneous fat area (range 3–31 cm2), FMD was 4.4 ± 3.5% and in the highest tertile (range 67–237 cm2) FMD was 6.8 ± 3.6% (p = 0.07, t-test). However, in multivariate analyses, no body composition measure showed a significant association with FMD for either the group as a whole or in ART-treated subjects. ART use, PI use, CD4 cell count, and HIV RNA levels were not associated with endothelial dysfunction by brachial FMD. A definitive association with measures of adiposity was not detected in multivariate analysis, suggesting that lipoatrophy may not be an important contributor to endothelial dysfunction in HIV-infected individuals on ART.
Several studies have reported improvements in lipids after antiretroviral therapy (ART) switches to tenofovir disoproxil fumarate (TDF)-containing regimens. We assessed lipid-lowering effects of TDF by adding it to a stable ART regimen in this double-blind, placebo-controlled crossover study. We demonstrated that non-HDL-C, LDL-C and TC improved significantly over TDF vs. placebo treatment in HIV-infected individuals with dyslipidemia. Adding TDF to stable, virologically-suppressive ART regimens improved lipid parameters, supporting a lipid-lowering effect of TDF.
Dyslipidemia; Tenofovir; Complications of Antiretroviral therapy
To determine whether high risk patients with hematuria receive evaluation according to guideline recommendations.
Materials and Methods
We recently performed a screening study for bladder cancer using a urine-based tumor marker in 1502 subjects at high risk based on age over 50, ≥10-year smoking history, and/or a 15 year or more environmental exposure. We evaluated use of urinalysis (UA) within 3 years preceding the screening study. Chart review was performed to determine if this subset with microhematuria received any additional evaluation.
Of 1502 study participants, routine urinalysis was performed in 73.2% and 164 (14.9%) subjects had documented hematuria (>3 RBCs/HPF) prior to inclusion. Of these, 42.1% had no further evaluation. Additional testing included repeat urinalysis (36%), urine culture (15.2%), cytology (10.4%), imaging (22.6% overall: 15.9% CT, 4.3% IVP; 2.4% MRI) and cystoscopy (12.8%).
Three subjects with microscopic hematuria (2%) were subsequently found to have bladder cancer during the screening study but were not referred for evaluation based on their hematuria. The source of hematuria was unknown in 65%, infection in 22%, benign prostatic enlargement in 10% and renal stone disease in 4% but these results are based on incomplete evaluation since only 12.8% underwent cystoscopy.
Subjects at high risk for bladder cancer based on ≥10 years of smoking or environmental exposure with microscopic hematuria are rarely evaluated thoroughly and only 12.8% were referred for urologic evaluation. Further studies are needed to evaluate both the utilization and effectiveness of guidelines for hematuria.
Hematuria; Guidelines Recommendations; bladder cancer
The World Health Organization (WHO) has recently recommended that antiretrovirals be initiated in all individuals with CD4 counts of less than 350 cells/mm3. For countries with resources too limited to expand care to all such patients, it would be of value to able to identify and target populations at highest risk of HIV progression. Renal disease has been identified as a risk factor for disease progression or death in some populations.
Times to meeting combination antiretroviral therapy (cART) initiation criteria (developing either a CD4 count < 200 cells/mm3 or WHO stage 3 or 4 disease) and overall mortality were evaluated in cART-naïve, HIV-infected Kenyan adults with CD4 cell counts ≥200/mm3 and with WHO stage 1 or 2 disease. Cox proportional hazard regression models were used to evaluate the associations between renal function and these endpoints.
We analyzed data of 7383 subjects with a median follow-up time of 59 (interquartile range, 27-97) weeks. In Cox regression analyses adjusted for age, sex, WHO disease stage, CD4 cell count and haemoglobin, estimated creatinine clearance (CrCl) < 60 mL/min was significantly associated with shorter times to meeting cART initiation criteria (HR 1.34; 95% CI, 1.23-1.52) and overall mortality (HR 1.73; 95% CI, 1.19-2.51) compared with CrCl ≥60 mL/min. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was associated with shorter times to meeting cART initiation criteria (HR 1.39; 95% CI, 1.22-1.58), but not with overall mortality. CrCl and eGFR remained associated with shorter times to cART initiation criteria, but neither was associated with mortality, in weight-adjusted analyses.
In this large natural history study, reduced renal function was strongly associated with faster HIV disease progression in adult Kenyans not initially meeting cART initiation criteria. As such, renal function measurement in resource-limited settings may be an inexpensive method to identify those most in need of cART to prevent progression to AIDS. The initial association between reduced CrCl, but not reduced eGFR, and greater mortality was explained by the low weights in this population.
We performed a single-arm, open-label pilot trial of the anti-inflammatory drug pentoxifylline to reduce systemic inflammation and improve endothelial function, measured by flow-mediated dilation of the brachial artery, in HIV-infected patients not requiring antiretroviral therapy. Pentoxifylline significantly reduced circulating levels of vascular cell adhesion molecule-1 and interferon-gamma-induced protein and significantly improved endothelial function during the 8 week trial. Pentoxifylline may reverse HIV-related endothelial dysfunction by directly inhibiting the endothelial leukocyte adhesion pathway.
HIV-1; Endothelium; Inflammation; Pentoxifylline
A key mandate of the Canadian Thoracic Society (CTS) is to promote evidence-based respiratory care through clinical practice guidelines (CPGs). To improve the quality and validity of the production, dissemination and implementation of its CPGs, the CTS has revised its guideline process and has created the Canadian Respiratory Guidelines Committee to oversee this process. The present document outlines the basic methodological tools and principles of the new CTS guideline production process. Important features include standard methods for choosing and formulating optimal questions and for finding, appraising, and summarizing the evidence; use of the Grading of Recommendations Assessment, Development and Evaluation system for rating the quality of evidence and strength of recommendations; use of the Appraisal of Guidelines for Research and Evaluation instrument for quality control during and after guideline development and for appraisal of other guidelines; use of the ADAPTE process for adaptation of existing guidelines to the local context; and use of the GuideLine Implementability Appraisal tool to augment implementability of guidelines. The CTS has also committed to develop guidelines in new areas, an annual guideline review cycle, and a new formal process for dissemination and implementation. Ultimately, it is anticipated that these changes will have a significant impact on the quality of care and clinical outcomes of individuals suffering from respiratory diseases across Canada.
Clinical practice guideline; Evidence-based medicine; Guideline adherence; Practice guidelines
Data on the number of individuals eligible for screening, and rates of screening, are necessary to assess national colorectal cancer (CRC) screening efforts. Such data are sparse for safety-net health systems.
A retrospective cohort study of individuals aged 50 to 75 served by a safety-net health system in Tarrant County, Texas was conducted to determine: (a) Size of the potential screen-eligible population aged 50–75, (b) Rate of screening over 5 years among individuals aged 54–75, and (c) Potential predictors of screening, including sex, race/ethnicity, insurance status, frequency of outpatient visits, and socioeconomic status.
Of 28,708 potential screen-eligible individuals, 20,416 were aged 54–75 and analyzed for screening; 22.0% were screened within the preceding 5 years. Female gender, Hispanic ethnicity, age 65–75, insurance status, and ≥2 outpatient visits were independently associated with screening. Access to care was an important factor: adjusted(aj) OR 2.57 (95% CI 2.23–2.98) for any insurance, ajOR 3.53 (95% CI 3.15–3.97) for ≥2 outpatient visits.
The screen-eligible population served by our safety-net health system was large, and the projected deficit in screen rates was substantial. Access to care was the dominant predictor of screening participation. If our results are replicable in similar health systems, the data suggest that screening guidelines and policy efforts must take into account the feasibility of proposed interventions. Strong advocacy for more resources for CRC screening interventions (including research into the best manner to provide screening to large populations) is needed.
Mass Screening; Colorectal Neoplasms; Medically Underserved Area
Because both renal disease and immune activation predict progression to AIDS, we evaluated the relationships between dipstick proteinuria ≥1+ [7% of 1012 subjects], CrCl <90mL/min [18% of 1071 subjects], and percentages of peripheral activated CD8 cells (CD8+CD38+HLA-DR+) in antiretroviral-naïve, HIV-infected subjects enrolled into AIDS Clinical Trials Group studies 384 and A5095. Proteinuria, but not CrCl, was associated with higher percentages of CD8+CD38+HLA-DR+ cells [55% vs. 50%; P=0.01], with even more pronounced differences in men and among Blacks and Hispanics. Proteinuria may be a surrogate measure of greater immune activation in HIV-infected patients initiating antiretroviral therapy.
HIV-1; proteinuria; renal failure; nephropathy; immune activation