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Background and aim: Opioid agonist medications for treatment of opioid use disorder (OUD) can improve human immunodeficiency virus (HIV) outcomes and reduce opioid use. We tested whether outpatient antagonist treatment with naltrexone could achieve similar results. Design Open‐label, non‐inferiority randomized trial. Setting: Six US HIV primary care clinics. Participants: A total of 114 participants with untreated HIV and OUD (62% male; 56% black, 12% Hispanic; positive for fentanyl (62%), other opioids (47%) and cocaine (60%) at baseline). Enrollment halted early due to slow recruitment. Intervention: HIV clinic‐based extended‐release naltrexone (XR‐NTX; n = 55) versus treatment as usual (TAU) with buprenorphine or methadone (TAU; n = 59). Measurements Treatment group differences were compared for the primary outcome of viral suppression (HIV RNA ≤ 200 copies/ml) at 24 weeks and secondary outcomes included past 30‐day use of opioids at 24 weeks. Findings Fewer XR‐NTX participants initiated medication compared with TAU participants (47 versus 73%). The primary outcome of viral suppression was comparable for XR‐NTX (52.7%) and TAU (49.2%) [risk ratio (RR) = 1.064; 95% confidence interval (CI) = 0.748, 1.514] at 24 weeks. Non‐inferiority could not be demonstrated, as the lower confidence limit of the RR did not exceed the pre‐specified margin of 0.75 in intention‐to‐treat (ITT) analysis. The main secondary outcome of past 30‐day opioid use was comparable for XR‐NTX versus TAU (11.7 versus 14.8 days; mean difference = −3.1; 95% CI = –8.7, 1.1) in ITT analysis. Among those initiating medication, XR‐NTX resulted in fewer days of opioid use compared with TAU in the past 30 days (6.0 versus 13.6, mean difference = −7.6; 95% CI = –13.8, −0.2). Conclusions: A randomized controlled trial found supportive, but not conclusive, evidence that human immunodeficiency virus clinic‐based extended‐release naltrexone is not inferior to treatment as usual for facilitating human immunodeficiency virus viral suppression. Participants who initiated extended‐release naltrexone used fewer opioids than those who received treatment as usual. [ABSTRACT FROM AUTHOR]

Background and aims HIV-infected people with substance use disorders are least likely to benefit from advances in HIV treatment. Integration of extended-release naltrexone (XR-NTX) into HIV clinics may increase engagement in the HIV care continuum by decreasing substance use. We aimed to compare (1) XR-NTX treatment initiation, (2) retention and (3) safety of XR-NTX versus treatment as usual (TAU) for treating opioid use disorder (OUD) and/or alcohol use disorder (AUD) in HIV clinics. Design Non-blinded randomized trial of XR-NTX versus pharmacotherapy TAU. Setting HIV primary care clinics in Vancouver, BC, Canada and Chicago, IL, USA. Participants Fifty-one HIV-infected patients seeking treatment for OUD ( n = 16), AUD ( n = 27) or both OUD and AUD ( n = 8). Measurements Primary outcomes were XR-NTX initiation (receipt of first injection within 4 weeks of randomization) and retention at 16 weeks. Secondary outcomes generated point estimates for change in substance use, HIV viral suppression [HIV RNA polymerase chain reaction (pcr) < 200 copies/ml] and safety. Findings Two-thirds (68%) of participants assigned to XR-NTX initiated treatment, and 88% of these were retained on XR-NTX at 16 weeks. In comparison, 96% of TAU participants initiated treatment, but only 50% were retained on medication at 16 weeks. Mean days of opioid use in past 30 days decreased from 17.3 to 4.1 for TAU and from 20.3 to 7.7 for XR-NTX. Mean heavy drinking days decreased from 15.6 to 5.7 for TAU and 12.5 to 2.8 for XR-NTX. Among those with OUD, HIV suppression improved from 67 to 80% for XR-NTX and 58 to 75% for TAU. XR-NTX was well tolerated, with no precipitated withdrawals and one serious injection-site reaction. Conclusions Extended-release naltrexone (XR-NTX) is feasible and safe for treatment of opioid use disorder and alcohol use disorder in HIV clinics. Treatment initiation appears to be lower and retention greater for XR-NTX compared with treatment as usual ( NCT01908062). [ABSTRACT FROM AUTHOR]

Investigators aware of prior treatment assignments may deliberately or subliminally influence rates of subsequent consent in randomised trials, thus introducing the possibility of bias. As a trial of Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) was not masked to health professionals other than ophthalmologists, this possibility was evaluated by comparing the incidence of refusal to participate in relation to the previous assignment. Over 5 years, the STOP-ROP trial enrolled 649 infants, while 394 eligible subjects refused. Enrolled infants were assigned to supplemental oxygen or control groups at 30 centres including 71 hospitals, and stratified into two severity strata of their retinopathy of prematurity. We studied whether the assignment of the previously enrolled infant to either the supplemental arm or the control arm of the study affected the incidence of refusal to participate in the study by the next eligible infant. We also evaluated the possibility that refusal based on the preceding assignment could have influenced either the baseline balance of eye severity and pulmonary status between the two arms of the study or the final outcome of the randomised trial. There was a significantly higher incidence of refusal if the prior enrollee had been assigned to the supplemental oxygen group (44%) as compared with the control group (34%, P = 0.004). This effect from the prior assignment was larger in the later half of the study. Irrespective of the prior enrollee’s assignment, refusal was more likely for more mature infants and those with milder baseline disease. Selection bias did not influence the ophthalmic or pulmonary findings at baseline, or the study outcomes. In incompletely masked studies, monitoring the distribution of refusers in relation to the previous assignment can reveal selection bias. Despite evidence of unequal refusal rates, the results of the STOP-ROP trial were not affected. [ABSTRACT FROM AUTHOR]

From 420 records of ethnic locations and movements since 2000 B. C., we computed vectors describing the proportions which peoples of the various European language families contributed to the gene pools within 85 land-based 5 × 5-degree quadrats in Europe. Using these language family vectors, we computed ethnohistorical affinities as arc distances between all pairs of the 85 quadrats. These affinities are significantly correlated with genetic distances based on 26 genetic systems, even when geographic distances, a common causative factor, are held constant. Thus, the ethnohistorical distances explain a significant amount of the genetic variation observed in modern populations. Randomizations of the records by chronology result in loss of significance for the observed partial correlation between genetics and ethnohistory, when geography is held constant. However, a randomization of records by location only results in reduced significance. Thus, while the historical sequence of the movements does not seem to matter in Europe, their geographic locations do. We discuss the implications of these findings. © 1993 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Dow and Cheverud (Am. J. Phys. Anthropol. 68:367-373, 1985) have published a statistical test for comparing any three similarity matrices. Using both simulations and analytical arguments, I establish that the presence of spatial autocorrelation, a common feature of geographically based anthropological and biological data, causes this test to reject too often. Increasing the spatial autocorrelation increases the spurious rejection rate. About 20% of the papers that reference Dow and Cheverud's paper have used their test with spatially autocorrelated data. Mantel's (Cancer Res. 27:209-220, 1967) method, when used as a test of spatial autocorrelation, is unaffected by these considerations, since its null hypothesis is that the data are uncorrelated. © 1992 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We introduce a statistical protocol for analyzing spatially varying data, including putative explanatory variables. The procedures comprise preliminary spatial autocorrelation analysis (from an earlier study), path analysis, clustering of the resulting set of path diagrams, ordination of these diagrams, and confirmatory tests against extrinsic information. To illustrate the application of these methods, we present incidence and mortality rates of 31 organ- and sex-specific cancers in Europe; these rates vary markedly with geography and type of cancer. Additionally, we investigated three factors (ethnohistory, genetics, and geography) putatively affecting these rates. The five variables were correlated separately for the 31 cancers over European reporting stations. We analyzed the correlations by path analysis, k-means clustering, and nonmetric multidimensional scaling; coefficients of the 31 path diagrams modeling the correlations vary substantially. To simplify interpretation, we grouped the diagrams into five clusters, for which we describe the differential effects of the three putative causes on incidence and mortality. When scaled, the path coefficients intergrade without marked gaps between clusters. Ethnic differences make for differences in cancer rates, even when the populations tested are ancient and complex mixtures. Path analysis usefully decomposes a structural model involving effects and putative causes, and estimates the magnitude of the model's components. Smooth intergradation of the path coefficients suggests the putative causes are the results of multiple forces. Despite this continuity of the path diagrams of the 31 cancers, clustering offers a useful segmentation of the continuum. Etiological and other extrinsic information on the cancers map significantly into the five clusters, demonstrating their epidemiological relevance., (Copyright 2003 Wiley-Liss, Inc.)