Systematic scoping review: Use of the faecal immunochemical test residual buffer to enhance colorectal cancer screening.

BACKGROUND: The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting colorectal cancer and cancer precursors is limited. There is growing interest in using the non-haemoglobin contents of FIT residual buffer to enhance colonic neoplasia detection. AIM: To establish from the literature a framework to catalogue candidate biomarkers within FIT residual buffer for non-invasive colorectal cancer screening. METHODS: The search strategy evaluated PubMed, Scopus, Web of Science, Embase, and Google Scholar for publications through 25 October 2023, with search terms including FIT, buffer, OC-sensor, biomarkers, microbiome, microRNA (miR), colon, rectum, screening, neoplasm, and early detection. Studies employing home-based collection samples using quantitative FIT first processed for haemoglobin were included. One author reviewed all articles; a second author completed a 20% full-text audit to ensure adherence to eligibility criteria. RESULTS: A broad search yielded 1669 studies and application of eligibility criteria identified 18 relevant studies. Multiple protein, DNA/RNA, and microbiome biomarkers (notably haptoglobin, miR-16, miR-27a-3p, miR-92a, miR-148a-3p, miR-223, miR-421, let-7b-5p, and Tyzzerella 4) were associated with colorectal neoplasia. Furthermore, studies highlighted the short-term stability of biomarkers for clinical use and long-term stability for research purposes. CONCLUSIONS: This scoping review summarises the framework and progress of research on stability of biomarkers in FIT residual buffer and their associations with colorectal neoplasia to guide opportunities for further confirmatory studies to enhance colorectal cancer screening.

Inactivated Poliovirus Vaccine Booster Reduces the Likelihood of COVID-19 Outcomes in Individuals Primed with Oral Poliovirus Vaccination.

Introduction: Prior research explores whether seasonal and childhood vaccines mitigate the risk of SARS-CoV-2 infection. Although there are trials investigating COVID-19 infection in response to the effects of the oral poliovirus vaccine (OPV), there has been no prior research assessing COVID-19 outcomes in recently immunized adults with the inactivated poliovirus vaccine (IPV). Methods: SARS-CoV-2 infection and COVID-19 symptoms were analyzed across a cohort of 282 adults who received an IPV booster. Bivariate and multivariate regression models explored associations among variables related to vaccination histories and COVID-19 outcomes. Results: One year post-IPV inoculation, participants who had never received OPV were more likely to test positive for SARS-CoV-2 and experience COVID-19 symptoms, compared to those who had previously received OPV (OR = 3.92, 95%CI 2.22-7.03, p < 0.001; OR = 4.45, 95%CI 2.48-8.17, p < 0.001, respectively). Those who had never received OPV experienced COVID-19 symptoms for 6.17 days longer than participants who had previously received OPV (95%CI 3.68-8.67, p < 0.001). Multivariate regression modeling indicated COVID-19 vaccination did not impact SARS-CoV-2 infection or COVID-19 symptoms in this sample of adults who had recently received IPV. Discussion: Findings suggest IPV may boost mucosal immunity among OPV-primed individuals, and COVID-19 vaccination may not provide additional protection among those who had received IPV. Future, larger-scale studies should measure the extent of protective effects against COVID-19 to inform public health policies in resource-deficient settings.

Vitamin D Supplementation and Prior Oral Poliovirus Vaccination Decrease Odds of COVID-19 Outcomes among Adults Recently Inoculated with Inactivated Poliovirus Vaccine.

BACKGROUND: Structural and functional commonalities between poliovirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggest that poliovirus inoculation may induce antibodies that mitigate the coronavirus disease (COVID-19). No known studies have evaluated COVID-19 risk factors in adults recently vaccinated against poliovirus. STUDY OBJECTIVE: Among adults with no history of COVID-19 infection or vaccination, who recently received an inactivated poliovirus vaccine (IPV), we sought to determine which biological factors and social determinants of health (SDOH) may be associated with (1) testing positive for SARS-CoV-2, (2) experiencing COVID-19 symptoms, and (3) a longer duration of COVID-19 symptoms. METHODS: The influence of biological factors and SDOH on SARS-CoV-2 infection and COVID-19 symptoms were evaluated among 282 adults recently inoculated with IPV. Participant-reported surveys were analyzed over 12 months post-enrollment. Bivariate and multivariate linear and logistic regression models identified associations between variables and COVID-19 outcomes. RESULTS: Adjusting for COVID-19 vaccinations, variants, and other SDOH, secondary analyses revealed that underlying conditions, employment, vitamin D, education, and the oral poliovirus vaccination (OPV) were associated with COVID-19 outcomes. The odds of testing positive for SARS-CoV-2 and experiencing symptoms were significantly reduced among participants who took vitamin D (OR 0.12 and OR 0.09, respectively). Unemployed or part-time working participants were 72% less likely to test positive compared with full-time workers. No prior dose of OPV was one of the strongest predictors of SARS-CoV-2 infection (OR 4.36) and COVID-19 symptoms (OR 6.95). CONCLUSIONS: Findings suggest that prophylactic measures and mucosal immunity may mitigate the risk and severity of COVID-19 outcomes. Larger-scale studies may inform future policies.

The Functional Implications of Broad Spectrum Bioactive Compounds Targeting RNA-Dependent RNA Polymerase (RdRp) in the Context of the COVID-19 Pandemic.

BACKGROUND: As long as COVID-19 endures, viral surface proteins will keep changing and new viral strains will emerge, rendering prior vaccines and treatments decreasingly effective. To provide durable targets for preventive and therapeutic agents, there is increasing interest in slowly mutating viral proteins, including non-surface proteins like RdRp. METHODS: A scoping review of studies was conducted describing RdRp in the context of COVID-19 through MEDLINE/PubMed and EMBASE. An iterative approach was used with input from content experts and three independent reviewers, focused on studies related to either RdRp activity inhibition or RdRp mechanisms against SARS-CoV-2. RESULTS: Of the 205 records screened, 43 studies were included in the review. Twenty-five evaluated RdRp activity inhibition, and eighteen described RdRp mechanisms of existing drugs or compounds against SARS-CoV-2. In silico experiments suggested that RdRp inhibitors developed for other RNA viruses may be effective in disrupting SARS-CoV-2 replication, indicating a possible reduction of disease progression from current and future variants. In vitro, in vivo, and human clinical trial studies were largely consistent with these findings. CONCLUSIONS: Future risk mitigation and treatment strategies against forthcoming SARS-CoV-2 variants should consider targeting RdRp proteins instead of surface proteins.

Surgery Versus Interferon Alpha-2b Treatment Strategies for Ocular Surface Squamous Neoplasia: A Literature-Based Decision Analysis.

PURPOSE: To compare treatment strategies for ocular surface squamous neoplasia (OSSN), ranging from surgical excision to empiric topical interferon alpha-2b (IFN-α2b). METHODS: A decision model was constructed to determine which of 4 treatment strategies minimized expected persistence/recurrence of disease in patients with OSSN: excision followed by repeat excision for positive surgical margins, excision followed by IFN-α2b for positive margins, incisional biopsy followed by IFN-α2b for positive biopsies, and empiric treatment with IFN-α2b. Probabilities were estimated from literature published between 1983 and 2015. Expected values for the probability of recurrence could range from 0 (no persistence/recurrence) to 1 (persistence/recurrence). Sensitivity analyses were performed for each variable. RESULTS: Excision followed by IFN-α2b for positive margins was estimated to minimize persistence/recurrence of OSSN (expected value 0.13 versus 0.17 for empiric IFN-α2b, 0.22 for excision-only, and 0.30 for incisional biopsy-directed IFN-α2b). The optimal strategy was sensitive to 3 variables: efficacy of IFN-α2b, recurrence after negative surgical margins, and accuracy of excisional biopsy. CONCLUSIONS: In our decision analysis using studies published between 1983 and 2015, surgical excision followed by IFN-α2b for positive margins is the favored strategy for minimizing persistence/recurrence of OSSN. Future prospective studies would add to the certainty of these conclusions.

Interventions to Improve the Quality of Outpatient Specialty Referral Requests: A Systematic Review.

Requests for outpatient specialty consultations occur frequently but often are of poor quality because of incompleteness. The authors searched bibliographic databases, trial registries, and references during October 2014 for studies evaluating interventions to improve the quality of outpatient specialty referral requests compared to usual practice. Two reviewers independently extracted data and assessed quality. Findings were qualitatively summarized for completeness of information relayed in a referral request within naturally emerging intervention categories. Of 3495 articles screened, 11 were eligible. All 3 studies evaluating software-based interventions found statistically significant improvements. Among 4 studies evaluating template/pro forma interventions, completeness was uniformly improved but with variable or unreported statistical significance. Of 4 studies evaluating educational interventions, 2 favored the intervention and 2 found no difference. One study evaluating referral management was negative. Current evidence for improving referral request quality is strongest for software-based interventions and templates, although methodological quality varied and findings may be setting specific.

Use of Protamine for Anticoagulation During Carotid Endarterectomy: A Meta-analysis.

IMPORTANCE: Protamine sulfate can be administered at the conclusion of carotid endarterectomy (CEA) to reverse the anticoagulant effects of heparin and to limit the risk for postoperative bleeding. Protamine use remains controversial owing to concern for increased thrombotic complications with its use. OBJECTIVE: To review the evidence for and against protamine use, both in its association with increased thrombotic complications and with decreased bleeding. DATA SOURCES: We searched Medline (1946-2014), EMBASE (1966-2014), Cochrane Library (1972-2014), clinical trial registries (World Health Organization International Clinical Trials Registry and clinicaltrials.gov), and abstracts from conferences of the Society of Vascular Surgery (2002-2014) and American Heart Association Scientific Sessions (1980-2014) in November 2014. No language restrictions were applied. STUDY SELECTION: We included clinical trials and observational studies comparing reversal of heparin with protamine sulfate vs no reversal in patients undergoing carotid revascularization and reporting stroke during hospitalization. Of 360 records screened, 12 studies (3%) of CEA were eligible for data pooling. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and assessed quality. Random-effects models were used to summarize relative risks (RRs). MAIN OUTCOME AND MEASURE: Stroke after CEA. RESULTS: We included 12 observational studies involving 10,621 patients in the meta-analysis. Event rates did not differ significantly between patients who received protamine vs those who did not for the following outcomes: stroke (RR, 0.84; 95% CI, 0.55-1.29; I(2) = 15%; 9 studies), myocardial infarction (RR, 0.89; 95% CI, 0.53-1.51; I(2) = 0%; 3 studies), or mortality (RR, 0.9, 95% CI, 0.62-1.29; I(2) = 0%; 7 studies). The use of protamine was associated with a significant decrease in major bleeding complications requiring reoperation (RR, 0.57; 95% CI, 0.39-0.84; I(2) = 32%; 10 studies). CONCLUSIONS AND RELEVANCE: Based on available evidence, the use of protamine following CEA is associated with a reduction in bleeding complications, without increasing major thrombotic outcomes, including stroke, myocardial infarction, or death.

Effect of just-in-time simulation training on provider performance and patient outcomes for clinical procedures: a systematic review.

Background: Providing simulation training directly before an actual clinical procedure-or 'just-in-time' (JiT)-is resource intensive, but could improve both provider performance and patient outcomes. Objectives: To assess the effects of JiT simulation training versus no JiT training on provider performance and patient complications following clinical procedures on patients. Study selection: We searched MEDLINE, Cochrane Library, CINAHL, PsycINFO, ERIC, ClinicalTrials.gov, simulation journals indexes and references of included studies during October 2014 for randomised trials, non-randomised trials and before-after studies comparing JiT simulation training versus no JiT training among providers performing clinical procedures. Findings were synthesised qualitatively. Findings: Of 1805 records screened, 8 studies comprising 3540 procedures and 1969 providers were eligible. 5 involved surgical procedures; the other 3 included paediatric endotracheal intubations, central venous catheter dressing changes, or infant lumbar puncture. Methodological quality was high. Of the 8 studies evaluating provider performance, 5 favoured JiT simulation training with 18-48% relative improvement on validated clinical performance scales, 16-20% relative reduction in surgical time and 12% absolute reduction in corrective prompts during central venous catheter dressing changes; 3 studies were equivocal with no improvement in intubation success, lumbar puncture success or urological surgery clinical performance scores. 3 studies evaluated patient complications; 1 favoured JiT simulation training with 45% relative reduction in central line-associated blood stream infections; 2 studies found no differences following intubation or laparoscopic nephrectomy. Conclusions: JiT simulation training improves provider performance, but currently available literature does not demonstrate a reduction in patient complications.

Aspirin versus anticoagulation for prevention of venous thromboembolism major lower extremity orthopedic surgery: a systematic review and meta-analysis.

BACKGROUND: Hip fracture surgery and lower extremity arthroplasty are associated with increased risk of both venous thromboembolism and bleeding. The best pharmacologic strategy for reducing these opposing risks is uncertain. PURPOSE: To compare venous thromboembolism (VTE) and bleeding rates in adult patients receiving aspirin versus anticoagulants after major lower extremity orthopedic surgery. DATA SOURCES: Medline, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library through June 2013; reference lists, ClinicalTrials.gov, and scientific meeting abstracts. STUDY SELECTION: Randomized trials comparing aspirin to anticoagulants for prevention of VTE following major lower extremity orthopedic surgery. DATA EXTRACTION: Two reviewers independently extracted data on rates of VTE, bleeding, and mortality. DATA SYNTHESIS: Of 298 studies screened, 8 trials including 1408 participants met inclusion criteria; all trials screened participants for deep venous thrombosis (DVT). Overall rates of DVT did not differ statistically between aspirin and anticoagulants (relative risk [RR]: 1.15 [95% confidence interval {CI}: 0.68-1.96]). Subgrouped by type of surgery, there was a nonsignificant trend favoring anticoagulation following hip fracture repair but not knee or hip arthroplasty (hip fracture RR: 1.60 [95% CI: 0.80-3.20], 2 trials; arthroplasty RR: 1.00 [95% CI: 0.49-2.05], 5 trials). The risk of bleeding was lower with aspirin than anticoagulants following hip fracture repair (RR: 0.32 [95% CI: 0.13-0.77], 2 trials), with a nonsignificant trend favoring aspirin after arthroplasty (RR: 0.63 [95% CI: 0.33-1.21], 5 trials). Rates of pulmonary embolism were too low to provide reliable estimates. CONCLUSION: Compared with anticoagulation, aspirin may be associated with higher risk of DVT following hip fracture repair, although bleeding rates were substantially lower. Aspirin was similarly effective after lower extremity arthroplasty and may be associated with lower bleeding risk. Journal of Hospital Medicine 2014;9:579-585. © 2014 Society of Hospital Medicine.

Cilostazol is associated with improved outcomes after peripheral endovascular interventions.

OBJECTIVE: Although cilostazol is commonly used as an adjunct after peripheral vascular interventions, its efficacy remains uncertain. We assessed the effect of cilostazol on outcomes after peripheral vascular interventions using meta-analytic techniques. METHODS: We searched MEDLINE (1946-2012), Cochrane CENTRAL (1996-2012), and trial registries for studies comparing cilostazol in combination with antiplatelet therapy to antiplatelet therapy alone after peripheral vascular interventions. Treatment effects were reported as pooled risk/hazard ratio (HR) with random-effects models. RESULTS: Two randomized trials and four retrospective cohorts involving 1522 patients met inclusion criteria. Across studies, mean age ranged from 65 to 76 years, and the majority of patients were male (64%-83%); mean follow-up ranged from 18 to 37 months. Most interventions were in the femoropopliteal segment, and overall, 68% of patients had stents placed. Pooled estimates demonstrated that the addition of cilostazol was associated with decreased restenosis (relative risk [RR], 0.71; 95% confidence interval [CI], 0.60-0.84; P < .001), improved amputation-free survival (HR, 0.63; 95% CI, 0.47-0.85; P = .002), improved limb salvage (HR, 0.42; 95% CI, 0.27-0.66; P < .001), and improved freedom from target lesion revascularization (RR, 1.36; 95% CI, 1.14-1.61; P < .001). There was no significant reduction in mortality among those receiving cilostazol (RR, 0.73; 95% CI, 0.45-1.19; P = .21). CONCLUSIONS: The addition of cilostazol to antiplatelet therapy after peripheral vascular interventions is associated with a reduced risk of restenosis, amputation, and target lesion revascularization in our meta-analysis of six studies. Consideration of cilostazol as a medical adjunct after peripheral vascular interventions is warranted, presuming these findings are broadly generalizable.

Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial.

OBJECTIVE: Streamlining the initiation of allopurinol could result in a cost benefit for a common medical problem and obviate the perception that no treatment is required once acute attacks have resolved. Our objective was to test the hypothesis that there is no difference in patient daily pain or subsequent attacks with early versus delayed initiation of allopurinol for an acute gout attack. METHODS: A total of 57 men with crystal-proven gout were randomized to allopurinol 300 mg daily or matching placebo for 10 days. All subjects received indomethacin 50 mg 3 times per day for 10 days, a prophylactic dose of colchicine 0.6 mg 2 times per day for 90 days, and open-label allopurinol starting at day 11. Primary outcome measures were pain on visual analogue scale (VAS) for the primary joint on days 1 to 10 and self-reported flares in any joint through day 30. RESULTS: On the basis of 51 evaluable subjects (allopurinol in 26, placebo in 25), mean daily VAS pain scores did not differ significantly between study groups at any point between days 1 and 10. Initial VAS pain scores for allopurinol and placebo arms were 6.72 versus 6.28 (P=.37), declining to 0.18 versus 0.27 (P=.54) at day 10, with neither group consistently having more daily pain. Subsequent flares occurred in 2 subjects taking allopurinol and 3 subjects taking placebo (P=.60). Although urate levels decreased rapidly in the allopurinol group (from 7.8 mg/dL at baseline to 5.9 mg/dL at day 3), sedimentation rates and C-reactive protein levels did not differ between groups at any point. CONCLUSIONS: Allopurinol initiation during an acute gout attack caused no significant difference in daily pain, recurrent flares, or inflammatory markers.

The effect of computers for weight loss: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The use of computers to deliver education and support strategies has been shown to be effective in a variety of conditions. We conducted a systematic review and meta-analysis to evaluate the impact of computer-based technology on interventions for reducing weight. METHODS: We searched MEDLINE, CENTRAL, CINAHL, PsycINFO, Google Scholar and ClinicalTrials.gov (all updated through June 2010) for randomized controlled trials evaluating the effect of computer-based technology on education or support interventions aimed at reducing weight in overweight or obese adults. We calculated weighted mean differences (WMD) and 95% confidence intervals (CI) using random effects models. RESULTS: Eleven trials with 13 comparisons met inclusion criteria. Based on six comparisons, subjects who received a computer-based intervention as an addition to the standard intervention given to both groups lost significantly more weight (WMD -1.48 kg, 95% CI -2.52, -0.43). Conversely, based on six comparisons, subjects for whom computer-based technology was substituted to deliver an identical or highly comparable intervention to that of the control group lost significantly less weight (WMD 1.47 kg, 95% CI 0.13, 2.81). Significantly different weight loss seen in "addition" comparisons with less than six months of follow-up (WMD -1.95 kg, 95% CI -3.50, -0.40, two comparisons) was not seen in comparisons with longer follow-up (-1.08 kg, 95% CI -2.50, 0.34, four comparisons). Analyses based on quality and publication date did not substantially differ. CONCLUSIONS: While the addition of computer-based technology to weight loss interventions led to statistically greater weight loss, the magnitude (<1.5 kg) was small and unsustained.

The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials.

BACKGROUND: HIV-associated lipodystrophy syndrome (HALS) is characterized by insulin resistance, abnormal lipid metabolism and redistribution of body fat. To date, there has been no quantitative summary of the effects of insulin sensitizing-agents for the treatment of this challenging problem. METHODS: We searched MEDLINE, the Cochrane Library, clinical trial registries, conference proceedings and references for randomized trials evaluating rosiglitazone, pioglitazone or metformin in patients with evidence of HALS (last update December 2009). Two reviewers independently abstracted data and assessed quality using a standard form. We contacted authors for missing data and calculated weighted mean differences (WMD) and 95% confidence intervals (CI) for each outcome. RESULTS: Sixteen trials involving 920 patients met inclusion criteria. Rosiglitazone modestly improved fasting insulin (WMD -3.67 mU/L; CI -7.03, -0.31) but worsened triglycerides (WMD 32.5 mg/dL; CI 1.93, 63.1), LDL (WMD 11.33 mg/dL; CI 1.85, 20.82) and HDL (WMD -2.91 mg/dL; CI -4.56, -1.26) when compared to placebo or no treatment in seven trials. Conversely, pioglitazone had no impact on fasting insulin, triglycerides or LDL but improved HDL (WMD 7.60 mg/dL; CI 0.20, 15.0) when compared to placebo in two trials. Neither drug favorably impacted measures of fat redistribution. Based on six trials with placebo or no treatment controls, metformin reduced fasting insulin (WMD -8.94 mU/L; CI -13.0, -4.90), triglycerides (WMD -42.87 mg/dL; CI -73.3, -12.5), body mass index (WMD -0.70 kg/m2; CI -1.09, -0.31) and waist-to-hip ratio (WMD -0.02; CI -0.03, 0.00). Three trials directly compared metformin to rosiglitazone. While effects on insulin were comparable, lipid levels and measures of fat redistribution all favored metformin. Severe adverse events were uncommon in all 16 trials. CONCLUSION: Based on our meta-analysis, rosiglitazone should not be used in HALS. While pioglitazone may be safer, any benefits appear small. Metformin was the only insulin-sensitizer to demonstrate beneficial effects on all three components of HALS.

Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis.

BACKGROUND & AIMS: Although anti-tumor necrosis factor (TNF) therapy can effectively treat Crohn's disease (CD), there is concern that it might increase the risk of non-Hodgkin's lymphoma (NHL). A meta-analysis was performed to determine the rate of NHL in adult CD patients who have received anti-TNF therapy and to compare this rate with that of a population-based registry and a population of CD patients treated with immunomodulators. METHODS: MEDLINE, EMBASE, Cochrane Collaboration, and Web of Science were searched. Inclusion criteria included randomized controlled trials, cohort studies, or case series reporting on anti-TNF therapy in adult CD patients. Standardized incidence ratios (SIR) were calculated by comparing the pooled rate of NHL with the expected rate of NHL derived from the Surveillance Epidemiology & End Results (SEER) database and a meta-analysis of CD patients treated with immunomodulators. RESULTS: Twenty-six studies involving 8905 patients and 21,178 patient-years of follow-up were included. Among anti-TNF treated subjects, 13 cases of NHL were reported (6.1 per 10,000 patient-years). The majority of these patients had previous immunomodulator exposure. Compared with the expected rate of NHL in the SEER database (1.9 per 10,000 patient-years), anti-TNF treated subjects had a significantly elevated risk (SIR, 3.23; 95% confidence interval, 1.5-6.9). When compared with the NHL rate in CD patients treated with immunomodulators alone (4 per 10,000 patient-years), the SIR was 1.7 (95% confidence interval, 0.5-7.1). CONCLUSIONS: The use of anti-TNF agents with immunomodulators is associated with an increased risk of NHL in adult CD patients, but the absolute rate of these events remains low and should be weighed against the substantial benefits associated with treatment.

Intravitreal triamcinolone acetonide injection for treatment of refractory diabetic macular edema: a systematic review.

OBJECTIVE: To compare intravitreal triamcinolone acetonide (IVTA) injection versus no treatment or sub-Tenon triamcinolone acetonide (STTA) injection in improving visual acuity (VA) of patients with refractory diabetic macular edema (DME; unresponsive to focal laser therapy). CLINICAL RELEVANCE: Diabetic macular edema is the leading cause of visual loss in diabetic retinopathy. Laser therapy has been the standard of care for patients with persistent or progressive disease. More recently, it has been suggested that IVTA injection may improve VA. METHODS AND LITERATURE REVIEWED: The following databases were searched: Medline (1950-September Week 2 2008), The Cochrane Library (Issue 3, 2008), and the TRIP Database (up to September 1, 2008), using no language or other limits. Randomized controlled trials were included that consisted of patients with refractory DME, those comparing IVTA injection with no treatment or STTA injection, those reporting VA outcomes, and those having a minimum follow-up of 3 months. RESULTS: In the 4 randomized clinical trials comparing IVTA injection with placebo or no treatment, IVTA injection demonstrated greater improvement in VA at 3 months, but the benefit was no longer significant at 6 months. Those who received IVTA injection had significantly higher IOP at 3 months and at 6 months. In the 2 randomized clinical trials comparing IVTA injection with STTA injection, IVTA injection demonstrated greater improvement in VA at 3 months, but not at 6 months. Intravitreal triamcinolone acetonide injection demonstrated no difference in IOP at 3 months or at 6 months. CONCLUSIONS: Intravitreal triamcinolone acetonide injection is effective in improving VA in patients with refractory DME in the short-term, but the benefits do not seem to persist in the long-term. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Press releases by academic medical centers: not so academic?

BACKGROUND: The news media are often criticized for exaggerated coverage of weak science. Press releases, a source of information for many journalists, might be a source of those exaggerations. OBJECTIVE: To characterize research press releases from academic medical centers. DESIGN: Content analysis. SETTING: Press releases from 10 medical centers at each extreme of U.S. News & World Report's rankings for medical research. MEASUREMENTS: Press release quality. RESULTS: Academic medical centers issued a mean of 49 press releases annually. Among 200 randomly selected releases analyzed in detail, 87 (44%) promoted animal or laboratory research, of which 64 (74%) explicitly claimed relevance to human health. Among 95 releases about primary human research, 22 (23%) omitted study size and 32 (34%) failed to quantify results. Among all 113 releases about human research, few (17%) promoted studies with the strongest designs (randomized trials or meta-analyses). Forty percent reported on the most limited human studies--those with uncontrolled interventions, small samples (<30 participants), surrogate primary outcomes, or unpublished data--yet 58% lacked the relevant cautions. LIMITATION: The effects of press release quality on media coverage were not directly assessed. CONCLUSION: Press releases from academic medical centers often promote research that has uncertain relevance to human health and do not provide key facts or acknowledge important limitations. PRIMARY FUNDING SOURCE: National Cancer Institute.

Benefits and risks of tight glucose control in critically ill adults: a meta-analysis.

CONTEXT: The American Diabetes Association and Surviving Sepsis Campaign recommend tight glucose control in critically ill patients based largely on 1 trial that shows decreased mortality in a surgical intensive care unit. Because similar studies report conflicting results and tight glucose control can cause dangerous hypoglycemia, the data underlying this recommendation should be critically evaluated. OBJECTIVE: To evaluate benefits and risks of tight glucose control vs usual care in critically ill adult patients. DATA SOURCES: MEDLINE (1950-2008), the Cochrane Library, clinical trial registries, reference lists, and abstracts from conferences from both the American Thoracic Society (2001-2008) and the Society of Critical Care Medicine (2004-2008). STUDY SELECTION: We searched for studies in any language in which adult intensive care patients were randomly assigned to tight vs usual glucose control. Of 1358 identified studies, 34 randomized trials (23 full publications, 9 abstracts, 2 unpublished studies) met inclusion criteria. DATA EXTRACTION AND ANALYSIS: Two reviewers independently extracted information using a prespecified protocol and evaluated methodological quality with a standardized scale. Study investigators were contacted for missing details. We used both random- and fixed-effects models to estimate relative risks (RRs). RESULTS: Twenty-nine randomized controlled trials totaling 8432 patients contributed data for this meta-analysis. Hospital mortality did not differ between tight glucose control and usual care overall (21.6% vs 23.3%; RR, 0.93; 95% confidence interval [CI], 0.85-1.03). There was also no significant difference in mortality when stratified by glucose goal ([1] very tight: < or = 110 mg/dL; 23% vs 25.2%; RR, 0.90; 95% CI, 0.77-1.04; or [2] moderately tight: < 150 mg/dL; 17.3% vs 18.0%; RR, 0.99; 95% CI, 0.83-1.18) or intensive care unit setting ([1] surgical: 8.8% vs 10.8%; RR, 0.88; 95% CI, 0.63-1.22; [2] medical: 26.9% vs 29.7%; RR, 0.92; 95% CI, 0.82-1.04; or [3] medical-surgical: 26.1% vs 27.0%; RR, 0.95; 95% CI, 0.80-1.13). Tight glucose control was not associated with significantly decreased risk for new need for dialysis (11.2% vs 12.1%; RR, 0.96; 95% CI, 0.76-1.20), but was associated with significantly decreased risk of septicemia (10.9% vs 13.4%; RR, 0.76; 95% CI, 0.59-0.97), and significantly increased risk of hypoglycemia (glucose < or= 40 mg/dL; 13.7% vs 2.5%; RR, 5.13; 95% CI, 4.09-6.43). CONCLUSION: In critically ill adult patients, tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk of hypoglycemia.

Risk for increased utilization and adverse health outcomes among men served by the Veterans Health Administration.

Using data from a nationally representative survey, we evaluated the prevalence of multiple risk factors known to predict increased health care utilization and adverse health outcomes, comparing U.S. men who rely solely on the Veterans Affairs Health Administration (VA) for health care to men in the general population. Adjusting for age and race, men who only use the VA were significantly more likely to have multiple socioeconomic and lifestyle risk factors including current smoking. Their self-reported health status was more often fair or poor and they were more likely to report the presence of multiple chronic diseases ranging from arthritis to previous heart attack to poor mental health. Although the finding that VA-only users are at elevated health risk was anticipated, our study now provides nationally representative estimates of the magnitude of these differences and reinforces the importance of accounting for them when making VA to non-VA comparisons.

Celebrity endorsements of cancer screening.

Celebrities often promote cancer screening by relating personal anecdotes about their own diagnosis or that of a loved one. We used data obtained from a random-digit dialing survey conducted in the United States from December 2001 through July 2002 to examine the extent to which adults of screening age without a history of cancer had seen or heard or been influenced by celebrity endorsements of screening mammography, prostate-specific antigen (PSA) testing, or sigmoidoscopy or colonoscopy. The survey response rate was 72% among those known to be eligible and 51% among potentially eligible people accounting for those who could not be contacted. A total of 360 women aged 40 years or older and 140 men aged 50 years or older participated in the survey. Most respondents reported they "had seen or heard a celebrity talk about" mammography (73% of women aged 40 years or older), PSA testing (63% of men aged 50 years or older), or sigmoidoscopy or colonoscopy (52% of adults aged 50 years or older). At least one-fourth of respondents who had seen or heard a celebrity endorsement said that the endorsement made them more likely to undergo mammography (25%), PSA testing (31%), or sigmoidoscopy or colonoscopy (37%).