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BACKGROUND: During the ongoing opioid epidemic, some Opioid Treatment Programs (OTPs) are unable to admit program applicants in a timely fashion. Interim methadone (IM) treatment (without routine counseling) is an effective approach to overcome this challenge when counseling capacity is inadequate to permit admissions within 14 days of request. It requires both federal and state approval and has been rarely utilized since its incorporation into the federal OTP regulations in 1993. METHODS: We evaluated the impact of Implementation Facilitation (IF) on OTPs providing timely admission to methadone treatment (i.e., within 14 days of request), adopting IM, and changing admissions procedures. IF included data collection on admission processes and an external facilitator who engaged OTP leadership, Local Champions through site visits, remote academic detailing, and feedback. Local Champions and State Opioid Treatment Authorities (SOTAs) participated in learning collaboratives. Using a modified stepped wedge design, six OTPs in four US states on the east and west coasts were randomly assigned to one of two clusters that staggered the timing of IF receipt. Study Phases included: Pre-Implementation, IF, and Sustainability. OTPs submitted data on treatment requests and admissions for 28 months (N = 3108 requests for treatment). RESULTS: Although none of the OTPs adopted IM, all six developed policies and procedures to enable its use. Some OTPs streamlined admissions processes prior to study launch and during the IF intervention. OTPs reduced admission delays over time, although there was substantial site heterogeneity. The IF Phase for the early cluster coincided with the onset of COVID-19, complicating the study. Rates of timely admission within 14 days of request were 56.2 % (Pre-Implementation), 55.8 % (IF), and 78.8 % (Sustainability). Compared to the Pre-Implementation Phase, the odds of timely admission were not significantly different during the IF Phase but significantly higher during the Sustainability Phase (OR = 2.35 [95 % CI = 1.34, 4.12]; p = 0.003). CONCLUSIONS: Committing to study participation and IF activities may have prompted some OTPs to change practices that improved timely admission. Attributing changes to IF should be done with caution considering study limitations. Data collection for the study spanned the COVID-19 pandemic, which complicates interpretation. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT04188977.

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This was a three group randomized clinical trial of interim methadone and patient navigation involving 225 pre-trial detainees with opioid use disorder in Baltimore. The HIV Risk Assessment Battery (RAB) was administered at baseline (in jail), and at 6 and 12 months post-release. Generalized linear mixed model analyses indicated the condition × time interaction effect failed to reach significance (ps > .05) for both the drug risk and sex risk subscale scores. Therefore, findings suggest that there were no intervention effects on drug or sex risk behaviors. However, increased use of cocaine at baseline was associated with increases in drug- (b = .04, SE = .02) and sex-risk (b = .01, SE = .003) behaviors. These results suggest that interventions targeting cocaine use among pre-trial detainees may serve as a means of reducing HIV risk associated with drug- and sex-risk behaviors.Clinical Trials Registration: Clinicaltrials.gov NCT02334215.

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BACKGROUND: Opioid use disorder is common among detainees in US jails, yet methadone treatment is rarely initiated. METHODS: This is a three-group randomized controlled trial in which 225 detainees in Baltimore treated for opioid withdrawal were assigned to: (1) interim methadone (IM) with patient navigation (IM + PN); (2) IM; or (3) enhanced treatment-as-usual (ETAU). Participants in both IM groups were able to enter standard methadone treatment upon release, while ETAU participants received an assessment/referral number. Follow-up assessments at 1, 3, 6, and 12 months post-release determined treatment enrollment, urine drug testing results, self-reported days of drug use, criminal activity, and overdose events. Generalized linear mixed modelling examined two planned contrasts: (1) IM groups combined vs. ETAU; and (2) IM + PN vs. IM. RESULTS: On an intention-to-treat basis, compared to ETAU, significantly more participants in the combined IM groups were in treatment 30 days post-release, while the IM + PN vs. IM groups did not significantly differ. By month 12, there were no significant differences in the estimated marginal means of enrollment in any kind of drug treatment (0.40 and 0.27 for IM + PN and IM groups, respectively, compared to 0.29 for ETAU). There were no significant differences for either contrast in opioid-positive tests, although all groups reported a sharp decrease in heroin use from baseline to follow-up. There were five fatal overdoses, but none occurred during methadone treatment. CONCLUSION: Initiating methadone treatment in jail was effective in promoting entry into community-based drug abuse treatment but subsequent treatment discontinuation attenuated any potential impact of such treatment.

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BACKGROUND: There is a need for screening and brief assessment instruments to identify primary care patients with substance use problems. This study's aim was to examine the performance of a two-step screening and brief assessment instrument, the TAPS Tool, compared to the WHO ASSIST. METHODS: Two thousand adult primary care patients recruited from five primary care clinics in four Eastern US states completed the TAPS Tool followed by the ASSIST. The ability of the TAPS Tool to identify moderate- and high-risk use scores on the ASSIST was examined using sensitivity and specificity analyses. RESULTS: The interviewer and self-administered computer tablet versions of the TAPS Tool generated similar results. The interviewer-administered version (at cut-off of 2), had acceptable sensitivity and specificity for high-risk tobacco (0.90 and 0.77) and alcohol (0.87 and 0.80) use. For illicit drugs, sensitivities were >0.82 and specificities >0.92. The TAPS (at a cut-off of 1) had good sensitivity and specificity for moderate-risk tobacco use (0.83 and 0.97) and alcohol (0.83 and 0.74). Among illicit drugs, sensitivity was acceptable for moderate-risk of marijuana (0.71), while it was low for all other illicit drugs and non-medical use of prescription medications. Specificities were 0.97 or higher for all illicit drugs and prescription medications. CONCLUSIONS: The TAPS Tool identified adult primary care patients with high-risk ASSIST scores for all substances as well moderate-risk users of tobacco, alcohol, and marijuana, although it did not perform well in identifying patients with moderate-risk use of other drugs or non-medical use of prescription medications. The advantages of the TAPS Tool over the ASSIST are its more limited number of items and focus solely on substance use in the past 3months.

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Many pharmaceuticals on the market suffer from two significant limitations to their activity: lack of specificity toward the pathological site and poor aqueous solubility. Both factors therefore require the application of a large total dose of a drug to achieve high local concentration, causing numerous off-target toxic effects. Consequently, the grand aim of targeted drug delivery - the often-referred "magic bullet" - promises to improve drug concentration at the target site and maximize therapeutic response. Nanomaterial drug delivery systems have been explored extensively in the recent years for just this purpose. In the field of medicine, nanocarriers (NCs) have the potential to improve the biodistribution and pharmacokinetic characteristics of drugs, thereby reducing side effects while improving the therapeutic effect of drugs. Many nanomaterials are exquisitely designed and possess potent properties, yet it is extremely important to note that a general understanding of the interaction of nanomaterials with biological systems is essential for any such model properties to be effective in vivo, since the body presents a host of biological 'barriers' that will be encountered drug NCs. This review offers a general overview of the different biological obstacles that a NC must negotiate before it can carry out its desired role as a medicinal agent. From this standpoint we suggest aspects that should be considered for the rational design of novel nanomaterials possessing physicochemical properties that are appropriate for therapeutic or theragnostic applications.

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A paired study in 10 autologous volunteer donors was undertaken to investigate the efficacy of adding prostaglandin E1 (PGE1) in vitro during routine platelet concentrate (PC) production. After 5 days storage, PCs prepared with PGE1 were compared with control PCs. In vivo platelet recovery, survival and biodistribution were determined following autologous infusion of indium-111 labelled platelets into volunteers, together with the in vitro evaluation of platelet function and biochemistry. PGE1 facilitated easier and faster platelet resuspension following centrifugation. After storage there were few significant in vitro differences between PCs prepared with PGE1 and control PCs. The artifactual leucocyte concentration was significantly lower in the presence of PGE1, suggesting less platelet aggregates had been formed during storage and beta-thromboglobulin release was significantly reduced by PGE1, 14.0 +/- 6.0 micrograms per 10(9) platelets compared with 22.3 +/- 9.8 micrograms per 10(9) platelets in control PCs, (P < 0.01), indicating PGE1 reduced both platelet aggregation and activation probably at the initial preparation stage, known to produce the greatest trauma. Initial in vivo platelet recovery for PCs prepared with PGE1 was similar to that of control PCs, 41.1 +/- 12.5% vs. 44.4 +/- 8.0%, respectively, and there were no differences in organ distribution at 24 h. However, in vivo multiple hit survival was reduced in the presence of PGE1, 5.8 +/- 1.6 days compared with 6.9 +/- 1.4 days in control PCs (P < 0.05). Despite the ability of PGE1 to facilitate platelet resuspension and inhibit platelet aggregation and activation during preparation of the PCs, the reduced in vivo survival time may preclude the use of PGE1 during routine PC preparation.

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Platelet concentrates (PCs), stored for 5 days in PL 2209, a new polyvinyl chloride (PVC) storage container plasticised with butyryl trihexyl citrate, were compared with those stored in PL 1240, a PVC platelet container plasticised with triethylhexyl trimellitate. In part 1 of the study, pooled platelet-rich plasma (PRP) was aliquoted into each type of pack and pH, pCO2, pO2, hypotonic shock response, aggregation responses, lactate, glucose and ATP concentrations, and lactate dehydrogenase and beta-thromboglobulin release were compared at days 1, 3 and 5. In part 2, 12 volunteers gave a unit of blood on two separate occasions and PCs produced by the PRP method were stored in PL 2209 or PL 1240 for 5 days before autologous reinfusion of a 111In-labelled sample. In vitro results demonstrated that PL 2209 was more gas permeable than PL 1240. In part 2 of the study, at day 5, pCO2 was 3.13 +/- 0.62 versus 5.14 +/- 0.69 (p < 0.001), whilst pO2 was not significantly different for PL 2209 versus PL 1240, respectively. pH was better maintained in PL 2209 than in PL 1240 (7.38 +/- 0.13 vs. 7.24 +/- 0.10, respectively, p < 0.01) after storage for 5 days. These results were confirmed by those from part 1. In vivo data were similar for PC stored in the two plastics with a multiple-hit recovery of 40.9 +/- 12.1% for PL 2209 and 37.4 +/- 11.3% for PL 1240, and a multiple-hit survival of 4.89 +/- 1.20 days and 5.28 +/- 2.06 days for PL 2209 and PL 1240, respectively. gamma-Camera imaging of volunteers showed similar biodistribution of radiolabelled platelets stored in each container. These results demonstrate that PL 2209 is a suitable container for storage of PCs for 5 days.

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It is important that, at the time of transfusion, platelets prepared by different techniques are effective in vivo and meet acceptable criteria. A paired study was undertaken in 8 volunteer donors to compare apheresis platelets collected on the COBE Spectra with platelets derived from the buffy coat of whole blood donations after 5 days storage. In vivo recovery, survival and biodistribution were determined following indium-111 labelling of the platelets and autologous infusion into volunteers together with the in vitro evaluation of platelet function and biochemistry. The in vivo and in vitro characteristics of both types of platelet concentrate were not significantly different. Both products were equally viable after 5 d storage and both were of an acceptable quality as judged by currently used platelet products. Mean platelet survival (multiple hit) was 5.4 d for the apheresis platelets and 6.9 d for the buffy coat derived platelets and maximum recovery in circulation was 28.1% and 34.8%, respectively. There was a significantly higher platelet yield, as expected, from apheresis and a 1.5 log lower level of white cell contamination. This would be advantageous for patients in need of prolonged or recurrent transfusions as the number of donor exposures and the risk of alloimmunisation or viral transmission would be reduced.

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Platelet concentrates (PCs) were stored for 4 days at 22 degrees C in 400 ml second-generation (PL1240) platelet packs with either constant agitation, manual mixing once every 24 h or without agitation at any time. After 4 days storage, in vivo recovery, survival and biodistribution were determined following indium-111 labelling of platelets and infusion into autologous volunteers. In vitro assays of platelet function and biochemistry were likewise carried out after 4 days storage. The PCs stored without agitation had significantly lower in vivo recoveries, pH and aggregation responses to ionophore A23187 and a combination of collagen and epinephrine and significantly higher beta-thromboglobulin and indium-111 release than the agitated PCs. The manually mixed PCs were not significantly different from the constantly agitated PCs. PCs mixed simply once every 24 h remained viable with active oxidative phosphorylation and a pH above 6.74 in all but 1 case indicating that PCs stored at 22 degrees C for up to 4 days with only intermittent mixing are satisfactory for transfusion. A change from constant agitation would reduce capital costs in mixing equipment and simplify the transport of PCs from the transfusion centre to small hospital blood banks.

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Using a paired study, in vivo and in vitro characteristics of apheresis platelets collected on a cell separator and single-donor whole-blood (recovered) platelets via platelet-rich plasma (PRP) were compared after storage for 5 days in similar plastic containers. Autologous platelets from each of 12 volunteers were labeled with 111Indium after storage and reinjected. There was no significant difference in circulating recovery between platelets prepared by the two methods, and only one of five models of survival showed a significant difference. Hypotonic shock recovery was significantly better in apheresis than recovered platelets (57.0% and 32.4%, respectively), whilst aggregation to ADP at 3.2 microM and 32 microM was significantly higher in recovered than in apheresis platelets (17.0% and 45.2% versus 7.8% and 32.9%, respectively). Lactate dehydrogenase (LDH) content was significantly higher in recovered platelets (143.3 versus 77.1 IU/10(11) platelets), but LDH release was similar (15.0% cf. 12.6%). There was no significant difference between the two platelet preparations for platelet concentration, pH, aggregation with the calcium ionophore A23187 or collagen plus epinephrine, or ATP content or release. beta-TG release was lower in apheresis platelets. Neither product was consistently better than the other for the parameters tested, but apheresis platelets have the advantage of lower donor exposure to the patient.

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Visual measures of stereotypy, margin time (thigmotaxis or wall-hugging), and center time were correlated with automated measures using a revised 16 beam version of the Digiscan Animal Activity Monitor System. Rats were injected with d-amphetamine (1.25, 2.5, 5.0 and 10.0 mg/kg), scopolamine (1.25 and 2.5 mg/kg) or saline and drugs were found to increase center time and decrease margin time in a dose-dependent manner, with the maximum effect occurring with 1.25 and 2.5 mg/kg, respectively. At higher doses, an opposite effect was observed. Extremely high correlations between visual and automated recordings of both margin time and center time were found. Since thigmotaxic or wall-hugging behavior has been used as an indicator of emotionality in rats, the results of the present study suggest that these two locomotor variables may be useful additions to the Digiscan multivariate analysis of locomotor behavior. It was also found that a redefinition of stereotypic behavior improved its correlation with visual measurements compared to earlier studies.

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