Search

Regular HIV testing enables early identification and treatment of HIV among at-risk men who have sex with men (MSM). Characterizing HIV testing needs for Internet-using MSM informs development of Internet-facilitated testing interventions. In this systematic review we analyze HIV testing patterns among Internet-using MSM in the United States who report, through participation in an online study or survey, their HIV status as negative or unknown and identify demographic or behavioral risk factors associated with testing. We systematically searched multiple electronic databases for relevant English-language articles published between January 1, 2005 and December 16, 2014. Using meta-analysis, we summarized the proportion of Internet-using MSM who had ever tested for HIV and the proportion who tested in the 12 months preceding participation in the online study or survey. We also identified factors predictive of these outcomes using meta-regression and narrative synthesis. Thirty-two studies that enrolled 83,186 MSM met our inclusion criteria. Among the studies reporting data for each outcome, 85 % (95 % CI 82-87 %) of participants had ever tested, and 58 % (95 % CI 53-63 %) had tested in the year preceding enrollment in the study, among those for whom those data were reported. Age over 30 years, at least a college education, use of drugs, and self-identification as being homosexual or gay were associated with ever having tested for HIV. A large majority of Internet-using MSM indicated they had been tested for HIV at some point in the past. A smaller proportion-but still a majority-reported they had been tested within the year preceding study or survey participation. MSM who self-identify as heterosexual or bisexual, are younger, or who use drugs (including non-injection drugs) may be less likely to have ever tested for HIV. The overall findings of our systematic review are encouraging; however, a subpopulation of MSM may benefit from targeted outreach. These findings indicate unmet needs for HIV testing among Internet-using MSM and identify subpopulations that might benefit from targeted outreach, such as provision of HIV self-testing kits.

Although female sex workers are known to be vulnerable to HIV infection, little is known about the epidemiology of HIV infection among this high-risk population in the United States. We systematically identified and critically assessed published studies reporting HIV prevalence among female sex workers in the United States. We searched for and included original English-language articles reporting data on the prevalence of HIV as determined by testing at least 50 females who exchanged sexual practices for money or drugs. We did not apply any restrictions on date of publication. We included 14 studies from 1987 to 2013 that reported HIV prevalence for a total of 3975 adult female sex workers. Only two of the 14 studies were conducted in the last 10 years. The pooled estimate of HIV prevalence was 17.3 % (95 % CI 13.5-21.9 %); however, the prevalence of HIV across individual studies varied considerably (ranging from 0.3 to 32 %) and statistical heterogeneity was substantial (I(2) = 0.89, Q = 123; p < 0.001). Although the variance across the 14 studies was high, prevalence was generally high (10 % or greater in 11 of the 14 included studies). Very few studies have documented the prevalence of HIV among female sex workers in the United States; however, the available evidence does suggest that HIV prevalence among this vulnerable population is high.

From 2010 to 2014, CDC and the Office of Population Affairs at the USDHHS collaborated on the development of clinical recommendations for providing quality family planning services. A high priority was placed on the use of existing scientific evidence in developing the recommendations, in accordance with IOM guidelines for how to develop "trustworthy" clinical practice guidelines. Consequently, a series of systematic reviews were developed using a transparent and reproducible methodology aimed at ensuring that the clinical practice guidelines would be based on evidence collected in the most unbiased manner possible. This article describes the methodology used in conducting these systematic reviews, which occurred from mid-2011 through 2012., (Copyright © 2015. Published by Elsevier Inc.)

Context: This systematic review evaluated the evidence on the impact of contraceptive counseling provided in clinical settings on reproductive health outcomes to provide information to guide national recommendations on quality family planning services., Evidence Acquisition: Multiple databases were searched during 2010-2011 for peer-reviewed articles published in English from January 1985 through February 2011 describing studies that evaluated contraceptive counseling interventions in clinical settings. Studies were excluded if they focused primarily on prevention of HIV or sexually transmitted infections, focused solely on men, or were conducted outside the U.S., Canada, Europe, Australia, or New Zealand., Evidence Synthesis: The initial search identified 12,327 articles, of which 22 studies (from 23 articles) met the inclusion criteria. Six studies examined the impact of contraceptive counseling among adolescents, with four finding a significant positive impact on at least one outcome of interest. Sixteen studies examined the impact of counseling among adults or mixed populations (adults and adolescents), with 11 finding a significant positive impact on at least one outcome of interest., Conclusions: Promising components of contraceptive counseling were identified despite the diversity of interventions and inability to compare the relative effectiveness of one approach versus another. The evidence base would be strengthened by improved documentation of counseling procedures; assessment of intervention implementation and fidelity to put study findings into context; and development and inclusion of more RCTs, studies conducted among general samples of women, and studies with sample sizes sufficient to detect important behavioral outcomes at least 12 months post-intervention., (Published by Elsevier Inc.)

Context: This systematic review evaluated the evidence on the impact of family planning reminder systems-interventions intended to remind patients of behaviors to achieve reproductive health goals (e.g., daily text messages reminding oral contraceptive [OC] users to take a pill)-to provide information to guide national recommendations on quality family planning services., Evidence Acquisition: Multiple databases including PubMed were searched during 2010-2011 for peer-reviewed articles published in English from January 1985 through February 2011 describing studies evaluating reminder systems to improve family planning outcomes. Studies were excluded if they focused primarily on HIV or sexually transmitted infection prevention, focused solely on men, or were conducted outside the U.S., Europe, Australia, or New Zealand., Evidence Synthesis: The initial search identified 16,129 articles, five of which met the inclusion criteria. Three studies examined the impact of OC reminder systems; two found a statistically significant positive impact on correct use. Two studies examined the impact of reminder systems among depot medroxyprogesterone acetate (DMPA) users; one found a statistically significant positive impact on correct use., Conclusions: Although mixed support was found for the effectiveness of reminder system interventions on correct use of OCs and DMPA, the highest-quality evidence yielded null findings. The evidence base would be strengthened by the development of additional studies, especially RCTs, which objectively measure outcomes, examine additional contraceptive methods, and have sufficient sample sizes to detect behavioral outcomes at least 12 months post-intervention., (Published by Elsevier Inc.)

Context: Educational interventions can help increase knowledge of available contraceptive methods, enabling individuals to make informed decisions and use contraception more effectively. This systematic review evaluated contraceptive education interventions to guide national recommendations on quality family planning services., Evidence Acquisition: Three databases (CINAHL, PubMed, and PsycINFO) were searched from 1985 through 2012 for peer-reviewed articles on educational interventions, with supplemental searches conducted through 2015. Primary outcomes were knowledge, participation in and comfort with decision making, and attitudes toward contraception. Secondary outcomes included contraceptive use behaviors and unintended pregnancy., Evidence Synthesis: Database searches in 2011 identified 5,830 articles; 17 met inclusion criteria and were abstracted into evidence tables. Searches in 2012 and 2015 identified four additional studies. Studies used a wide range of tools (decision aids, written materials, audio/videotapes, and interactive games), with and without input from a healthcare provider or educator. Of 15 studies that examined the impact of educational interventions on knowledge, 14 found significant improvement using a range of tools, with and without input from a healthcare provider or educator. Fewer studies evaluated outcomes related to decision making, attitudes toward contraception, contraceptive use behaviors, or unintended pregnancy., Conclusions: Results from this systematic review are consistent with evidence from the broader healthcare field suggesting that a range of educational interventions can increase knowledge. Future studies should assess what aspects of educational interventions are most effective, the extent to which it is necessary to include a healthcare provider or educator, and the extent to which educational interventions can impact behaviors., (Published by Elsevier Inc.)

Background: Men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV) and there is evidence that this population is participating in increasingly risky sexual behavior. These changes are occurring in the context of new modes of online social interaction-many MSM now report first meeting their sex partners on the Internet. Better monitoring of key behavioral indicators among MSM requires the use of surveillance strategies that capitalize on these new modes of interaction. Therefore, we developed an annual cross-sectional behavioral survey of MSM in the United States, the American Men's Internet Survey (AMIS)., Objective: The purpose of this paper was to provide a description of AMIS methods. In addition we report on the first cycle of data collection (December 2013 through May 2014; AMIS-2013) on the same key indicators used for national HIV behavioral surveillance., Methods: AMIS-2013 recruited MSM from a variety of websites using banner advertisements or email blasts. Adult men currently residing in the United States were eligible to participate if they had ever had sex with a man. We examined demographic and recruitment characteristics using multivariable regression modeling (P<.05) stratified by the participants' self-reported HIV status., Results: In the AMIS-2013 round, 79,635 persons landed on the study page and 14,899 were eligible, resulting in 10,377 completed surveys from MSM representing every US state. Participants were mainly white, 40 years or older, living in the US South, living in urban areas, and recruited from a general social networking website. Self-reported HIV prevalence was 10.73% (n=1113). Compared to HIV-negative/unknown status participants, HIV-positive participants were more likely to have had anal sex without a condom with any male partner in the past 12 months (72.24% versus 61.24%, respectively; P<.001) and more likely to have had anal sex without a condom with their last male sex partner who was discordant/unknown HIV status (42.95% versus 13.62%, respectively; P<.001). Illicit substance use in the past 12 months was more likely to be reported by HIV-positive participants than HIV-negative/unknown status participants (39.17% versus 26.85%, respectively; P<.001). The vast majority of HIV-negative/unknown status participants (84.05%) had been previously HIV tested, but less than half (44.20%) had been tested in the past 12 months. Participants 18-24 years of age were more likely than those 40 years or older to have had anal sex without a condom with a discordant/unknown HIV status partner, were more likely to report substance use, and were less likely to have been HIV tested. Compared to general social networking, those from a geospatial social networking website were more likely to have reported all risk behaviors but were more likely to have been HIV tested., Conclusions: The first round of AMIS generated useful behavioral measures from more than 10,000 MSM Internet users. Preliminary findings identified some subgroups of MSM Internet users that are at potentially higher risk of HIV acquisition/transmission. AMIS will provide an ongoing data source for examining trends in sexual risk behavior of MSM. This will help to plan and monitor the impact of programs to improve this population's health.

Increased efforts in comparative effectiveness research (CER) (comparing various health care intervention and treatment options) are being used to inform health care delivery. While CER research itself is an important step in developing best practices in health care, it is not enough to ensure success. The knowledge must also be successfully disseminated to increase adoption and implementation of practices. To ensure the greatest benefits of successful interventions, it is essential to understand which dissemination strategies are effective and under what conditions. This article provides the background and methodology used in a large-scale, 2-year study aimed at determining how knowledge gained from CER research may be most effectively disseminated to those responsible for delivering behavioral health services. The study takes an important step toward addressing the gaps in dissemination and translation of CER.

This randomized controlled trial examined the influence of two strategies (informational packets alone and in conjunction with Webinars) aimed at increasing the adoption of motivational interviewing (MI), a patient-centered behavioral health practice supported by evidence from comparative effectiveness studies, among community health organizations responsible for delivering mental and behavioral health services. Data were obtained from 311 directors and staff across 92 community organizations. Hierarchical linear modeling was used to examine changes in decision to adopt MI. The mediating effects of multiple contextual variables were also examined. Results showed that both strategies positively influenced the decision to adopt. The positive impact on decision to adopt was significantly greater among individuals that received informational packets in conjunction with Webinars. Baseline attitudes toward evidence-based practices and pressures for change appeared to mediate this effect.

Background: Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term effectiveness and safety, particularly the risk of tolerance, dependence, or abuse., Objectives: To assess safety, efficacy, and effectiveness of opioids taken long-term for CNCP., Search Strategy: We searched 10 bibliographic databases up to May 2009., Selection Criteria: We searched for studies that: collected efficacy data on participants after at least 6 months of treatment; were full-text articles; did not include redundant data; were prospective; enrolled at least 10 participants; reported data of participants who had CNCP. Randomized controlled trials (RCTs) and pre-post case-series studies were included., Data Collection and Analysis: Two review authors independently extracted safety and effectiveness data and settled discrepancies by consensus. We used random-effects meta-analysis' to summarize data where appropriate, used the I(2) statistic to quantify heterogeneity, and, where appropriate, explored heterogeneity using meta-regression. Several sensitivity analyses were performed to test the robustness of the results., Main Results: We reviewed 26 studies with 27 treatment groups that enrolled a total of 4893 participants. Twenty five of the studies were case series or uncontrolled long-term trial continuations, the other was an RCT comparing two opioids. Opioids were administered orally (number of study treatments groups [abbreviated as "k"] = 12, n = 3040), transdermally (k = 5, n = 1628), or intrathecally (k = 10, n = 231). Many participants discontinued due to adverse effects (oral: 22.9% [95% confidence interval (CI): 15.3% to 32.8%]; transdermal: 12.1% [95% CI: 4.9% to 27.0%]; intrathecal: 8.9% [95% CI: 4.0% to 26.1%]); or insufficient pain relief (oral: 10.3% [95% CI: 7.6% to 13.9%]; intrathecal: 7.6% [95% CI: 3.7% to 14.8%]; transdermal: 5.8% [95% CI: 4.2% to 7.9%]). Signs of opioid addiction were reported in 0.27% of participants in the studies that reported that outcome. All three modes of administration were associated with clinically significant reductions in pain, but the amount of pain relief varied among studies. Findings regarding quality of life and functional status were inconclusive due to an insufficient quantity of evidence for oral administration studies and inconclusive statistical findings for transdermal and intrathecal administration studies., Authors' Conclusions: Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive. Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.

Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term efficacy and adverse events (including addiction). We systematically reviewed the clinical evidence on patients treated with opioids for CNCP for at least six months. Of 115 studies identified by our search of eleven databases (through April 7, 2007), 17 studies (patients [n]=3,079) met inclusion criteria. Studies evaluated oral (studies [k]=7; n=1,504), transdermal (k=3; n=1, 993), and/or intrathecal (k=8; n=177) opioids. Many patients withdrew from the clinical trials due to adverse effects (oral: 32.5% [95% confidence interval (CI), 26.1%-39.6%]; intrathecal: 6.3% [95% CI, 2.9%-13.1%]; transdermal: 17.5% [95% CI, 6.5%-39.0%]), or due to insufficient pain relief (oral: 11.9% [95% CI, 7.8%-17.7%]; intrathecal: 10.5% [95% CI, 3.5%-27.4%]; transdermal: 5.8% [95% CI, 4.2%-7.3%]). Signs of opioid addiction were reported in only 0.05% (1/2,042) of patients and abuse in only 0.43% (3/685). There was an insufficient amount of data on transdermal opioids to quantify pain relief. For patients able to remain on oral or intrathecal opioids for at least six months, pain scores were reduced long-term (oral: standardized mean difference [SMD] 1.99, 95% CI, 1.17-2.80; intrathecal: SMD 1.33, 95% CI, 0.97-1.69). We conclude that many patients discontinue long-term opioid therapy due to adverse events or insufficient pain relief; however, weak evidence suggests that oral and intrathecal opioids reduce pain long-term in the relatively small proportion of individuals with CNCP who continue treatment.

Background: Methods for describing one's confidence in the available evidence are useful for end-users of evidence reviews. Analysts inevitably make judgments about the quality, quantity consistency, robustness, and magnitude of effects observed in the studies identified. The subjectivity of these judgments in several areas underscores the need for transparency in judgments., Discussion: This paper introduces a new system for rating medical evidence. The system requires explicit judgments and provides explicit rules for balancing these judgments. Unlike other systems for rating the strength of evidence, our system draws a distinction between two types of conclusions: quantitative and qualitative. A quantitative conclusion addresses the question, "How well does it work?", whereas a qualitative conclusion addresses the question, "Does it work?" In our system, quantitative conclusions are tied to stability ratings, and qualitative conclusions are tied to strength ratings. Our system emphasizes extensive a priori criteria for judgments to reduce the potential for bias. Further, the system makes explicit the impact of heterogeneity testing, meta-analysis, and sensitivity analyses on evidence ratings. This article provides details of our system, including graphical depictions of how the numerous judgments that an analyst makes can be combined. We also describe two worked examples of how the system can be applied to both interventional and diagnostic technologies., Summary: Although explicit judgments and formal combination rules are two important steps on the path to a comprehensive system for rating medical evidence, many additional steps must also be taken. Foremost among these are the distinction between quantitative and qualitative conclusions, an extensive set of a priori criteria for making judgments, and the direct impact of analytic results on evidence ratings. These attributes form the basis for a logically consistent system that can improve the usefulness of evidence reviews.

Background: Uncertainty continues to surround the relative benefits and harms of conventional coronary artery bypass grafting (CABG) and off-pump coronary artery bypass grafting (OPCABG). Possible reasons are that high-quality studies have not comprehensively examined relevant patient outcomes and have enrolled a limited range of patients. Some studies may have been too small to detect clinically important differences in patient outcomes. The present study addresses these issues using meta-analysis., Methods: We comprehensively retrieved randomized and nonrandomized controlled studies according to predetermined criteria. We performed meta-analyses for each outcome and empirically determined whether potential biases that might result from differences in study design or patient characteristics actually biased a study's results. We also conducted sensitivity analyses and tested for publication bias., Results: Rates of perioperative myocardial infarction, stroke, reoperation for bleeding, renal failure, and mortality were lower after OPCABG than after CABG. Reductions in length of hospital stay, atrial fibrillation, and wound infection were also associated with OPCABG, but statistically significant differences among study results for these outcomes could not be explained by available information. Midterm (3 to 25 months) angina recurrence did not appear to differ between treatments; a trend was noticed toward lower reintervention rates with CABG, and a trend toward lower overall mortality with OPCABG, at least when performed at experienced centers. These midterm outcome results require confirmation., Conclusions: Off-pump coronary artery bypass grafting appears to reduce length of hospital stay, operative morbidity, and operative mortality relative to on-pump CABG. More studies are required before firm conclusions can be drawn concerning the effect of OPCABG on midterm mortality, angina recurrence, and repeat intervention.

The time course of recovery of spatial resolution following adaptation to a uniform field was measured for test probes presented at lower illuminance than the adapting field. Six observers were tested in a Maxwellian-view system using 20 degrees adapting fields of 1.6-2.6 log photopic trolands. Test stimuli were 7 degrees, 250 ms Gabor patches (1 and 6 cpd) of mean retinal illuminance 2-3 log units lower than the adapting field. During the 9 s after adapting field offset, contrast thresholds for orientation discrimination followed an exponential-decay function and showed longer recovery times for larger illuminance decrements and higher spatial frequency.

Scotopic contrast sensitivity functions (CSFs) were measured for 50 observers between the ages of 20 and 88 years. Using a maximum-likelihood, 2-alternative, temporal forced-choice threshold-estimation algorithm, scotopic CSFs were measured at 7 spatial frequencies ranging from 0.2 to 3.0 cpd, with mean retinal illuminance equated for observers at -0.85 log scotopic Trolands. For each stimulus condition, eight cycles of a horizontal sinusoidal grating were presented within +/- 1 S.D. of a 2-D Gaussian-spatial envelope and within a 1-s Gaussian-temporal envelope. Stimuli were centered on the nasal retina along the horizontal meridian 6 degrees from the fovea. Scotopic CSFs were found to be low-pass. Statistically significant age-related declines in contrast sensitivities were found for spatial frequencies at or below 1.2 cpd. There was also a statistically significant decrease in the high frequency cut-off with age (P < 0.01). An explanation of these results in terms of optical factors is rejected, while the results are consistent with age-related changes in the magnocellular pathway.

Objective: Despite early interest in contrast sensitivity as a screening test for ophthalmic disease, most published opinion suggests that there is no benefit over conventional measurement of visual acuity. Taking a primary care perspective of screening, the authors evaluated the ability to discriminate those with any diagnosed ophthalmic disease in a large sample representative of the general population., Design: Retrospective analysis of a clinical, cross-sectional survey. Snellen visual acuity, contrast sensitivity (Arden plates, American Optical contrast sensitivity test), and ophthalmic diagnosis were reported previously., Participants: A sample of 3283 subjects, all aged at least 50 years, were selected randomly from residents of a health district in Sydney, Australia. Ophthalmologic diagnosis (ophthalmic disease presence/absence) had been confirmed for 2522 of these subjects., Main Outcome Measures: Signal detection techniques (the receiver-operating characteristics function [ROC], quality ROC [QROC], and weighted kappa coefficient of association [kappa(r)]) were used to evaluate test discriminability., Results: Because analyses of right and left eyes were almost identical, only right eye results are presented. Advantages of kappa(r) over ROC were shown. Discrimination of those with diagnosed ophthalmic disease from those without ophthalmic disease was best with Arden plate 7 (kappa0.5 = 0.93) and was better than distance Snellen visual acuity (kappa0.5 = 0.59). Arden plate 7 (6.4 cyc/deg) correctly assigned 96% of subjects at its optimal pass-fail criterion., Conclusions: In the primary care setting, a person older than 50 years of age with reduced contrast sensitivity, as determined by Arden plate 7, requires extra care in subsequent examinations because this person is likely to have an ophthalmic disease.

A prospective study was carried out to investigate acquired colour-vision deficits in diabetics using an automated, computer-controlled, cathode-ray-tube based test of chromatic contrast. Chromatic-contrast thresholds estimates were measured along both a red/ green (constant S-cone) confusion axis and a tritan (constant M/L-cone) confusion axis for 305 eyes of 305 diabetics. The diabetic data were partitioned into groups based on a clinical categorisation of retinopathy. The diabetic data were compared with both age-matched and 'lens-equated' control data obtained from a bank of 347 normal subjects. Further analysis of differences between diabetic-status groups was performed. Associations between chromatic contrast threshold estimates and age, duration of disease, and severity of both macular oedema and ischaemia were investigated. The diabetic group was found to have significantly reduced chromatic-contrast threshold estimates when compared with normal controls, even in the absence of retinopathy. This reduction in chromatic contrast was predominantly tritanopic in nature. Interestingly, no reduction in red/green chromatic-contrast threshold estimate was found in diabetics without retinopathy. The tritan deficit seen in diabetics without retinopathy was strongly correlated with duration of disease, but when adjustments were made to account for the effects of duration-dependent lens yellowing, the tritan deficit was no longer apparent. A correlation between both the severity of macular oedema and severity of ischaemia with chromatic-contrast loss was established. Acquired reductions in both red/green and tritan chromatic-contrast threshold estimates seen in diabetics are strongly correlated with the severity of retinopathy. The results provide evidence that the specific tritan deficits seen in diabetics can be explained by the effects of lens yellowing rather than by selective damage of the blue cone system as has been hypothesised by other groups. The results provide support for the potential use of automated CRT-based tests of colour vision in diabetic retinopathy screening protocols.

Automated colour vision testing in pseudophakes showed unexpected results. Chromatic discrimination sensitivity was measured in 22 diabetic pseudophakes with no retinopathy, 23 diabetic pseudophakes with background retinopathy and 34 non-diabetic pseudophakes. These results were compared with those in age-matched normal and diabetic phakic subjects, all of whom had good vision. The diabetics were also matched for retinopathy grading and duration of diabetes. In all three groups, red-green discrimination sensitivity was worse in the pseudophakes when compared with the corresponding phakic subjects (normals, p < 0.001; no retinopathy, p = 0.467; background retinopathy, p = 0.057). However, tritan vision was marginally worse in the normal pseudophake group but was better in the two diabetic pseudophake groups, when compared with phakic controls. This may be due to a reduction in tritan sensitivity in age-matched phakic controls from the effects of increased lens yellowing with age.

Our experience of patients with dysthyroid eye disease shows that normal chromatic discrimination sensitivity precludes the diagnosis of optic nerve compression (31 patients), and that clinically confirmed optic nerve compression is invariably associated with decreased chromatic discrimination sensitivity thresholds (8 patients). Dysthyroid patients enrolled in this study underwent automated achromatic contrast and chromatic discrimination sensitivity testing on presentation, with repeat assessment of those patients suspected of developing optic nerve compression. If chromatic discrimination sensitivity was decreased, patients were followed up more frequently. If abnormal chromatic discrimination sensitivity was accompanied by a relative afferent pupillary defect (RAPD) or decreased Snellen visual activity (VA), then optic nerve decompression was performed. The automated chromatic discrimination sensitivity test described represents a quick, reproducible and cheap clinical test which we feel is of value in assessing patients with dysthyroid eye disease. We suggest that sequential chromatic discrimination sensitivity assessment is a sensitive and effective way of monitoring patients at risk of dysthyroid optic neuropathy.

We have developed and extensively assessed an automated chromatic discrimination test which can be used to screen effectively a diabetic population for sight threatening diabetic eye disease. Equiluminant, sinusoidal, low spatial frequency, chromatic gratings are produced along a tritan confusion axis under computer software control on a high resolution CRT. The correct position of the tritan axis in colour space was calibrated using subjects whilst they were transiently tritanopic. The minimum amplitude about a neutral "grey point" along the tritan confusion axis at which a subject can just distinguish a grating is found using a double staircase reversal algorithm. This measure is taken as the Tritan Discrimination Sensitivity and it is this that we use to flag those diabetics with severe diabetic retinopathy. This computerised tritan discrimination test is quick, non-invasive, easy to operate, inexpensive and reliable. The test-retest reliability coefficient (rho) is 0.92. The tritan discrimination test effectively identifies those diabetics who have or are most at risk of developing severe diabetic retinopathy. The sensitivity of the test for the detection of maculopathy, ischaemic retinopathy (pre-proliferative), and proliferative retinopathy is 97%, 65%, and 93%, respectively. The corrected specificity of the test is 83%. We conclude that the tritan discrimination test has potential for use as a valuable screening tool for the early detection and treatment of severe diabetic retinopathy.

2'-Deoxy-2'-isocyano-1-beta-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2'-azido-2'-deoxy-1-beta-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2'-deoxy-2'-isocyanocytidine (14b) failed due to the insertion of the 2'-alpha isocyano group into the 3'-OH group, affording the 2',3'-oxazoline derivative 15b. Stability of the isocyano derivative 6a and 2',3'-oxazoline derivative 15a under basic and acidic conditions were examined. The isocyano group in 6a was stable in basic conditions but unstable even in weakly acidic conditions to furnish the corresponding 2'-beta formamide derivative 17. Compound 15a was easily hydrolyzed the corresponding 2'-alpha formamide derivative 16 on treatment with H2O at room temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor volume inhibition.