A trial of implementation facilitation to increase timely admission to methadone treatment.

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.

HIV-Risk Behavior Among Adults with Opioid Use Disorder During 12 Months Following Pre-trial Detention: Results from a Randomized Trial of Methadone Treatment.

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.

Methadone treatment of arrestees: A randomized clinical trial.

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.

Identifying substance misuse in primary care: TAPS Tool compared to the WHO ASSIST.

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.

Impact of type 1 diabetes mellitus and celiac disease on nutrition and quality of life.

OBJECTIVE: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are autoimmune diseases and have similar genetic patterns. T1DM treatment is based on diet, physical activity and insulin therapy, whereas CD depends on dietary changes with restriction of wheat, rye and barley. The aim of the study was to evaluate the quality of life (QoL) of individuals with the association of T1DM and CD, to characterize their nutritional status and to compare it with those with only one disease and healthier controls. SUBJECTS/METHODS: Sixty patients controlled by sex, age and body mass index (BMI) were stratified by previous diagnosis in: T1DM and CD (DMCD group); T1DM (DM group); CD (CD group); or healthy participants (HC). The SF-36 questionnaire was applied to assess psychological well being and results were compared with glycemic control and presence of complications related to diabetes, adhesion to gluten-free diet (GFD). Nutritional status and body mass composition were determined by BMI, waist circumference, bioimpedance, general laboratory tests and whole-body densitometry. RESULTS: The time of diagnosis of T1DM was similar between DMCD and DM groups; however, the duration of CD was significantly higher in the CD group compared with DMCD. The SF-36 analysis revealed statistically significant differences between DM and HC groups in two domains: general health (P=0.042) and energy/vitality (P=0.012). QoL was also correlated with compliance to a GFD, and scores were similar in both groups: DMCD and CD. Forty percent of individuals in the CD group had visceral fat area above 100 cm2, as opposed to 20% in the other groups. CONCLUSIONS: Individuals of DMCD group had similar scores to DM, CD and HC on QoL, as well as on their nutritional status and bone metabolism. Thereby, we should conclude that the association of T1DM and CD did not deteriorate their health status.

Decreasing the variability observed in urine analysis.

Urine analysis is affected significantly by biological variability. The objective of this study was to study the feasibility of reducing the biological variability of excretion of various analytes in urine, especially albumin in children with diabetes, by mixing small volumes of early morning samples. Twenty-two male children with type 1 diabetes collected early morning aliquots of approximately 10 ml of urine on 3 consecutive days and kept them refrigerated in sealed containers. The urine collection was repeated every 4-6 months in the diabetic children. Ten normal children and 10 normal adults participated as controls. The specimens were analyzed individually and as mixed samples for each subject. Mixing the 3 urine samples before analysis decreased the biological variability of all urine assays (albumin, glucose, creatinine, total protein, potassium). The diabetic children had 3 times higher variability of urine albumin (as a ratio to creatinine) compared to normal children, when the urine samples were collected individually (61% vs 19%, respectively). The variability in the diabetic children decreased when the 3 specimens were analyzed as a single sample after mixing, especially when urine albumin was expressed as a ratio to creatinine. Blood glycated hemoglobin levels correlated better with urine glucose levels when 3 urine samples were mixed before analysis.

Nutritional rickets in African American breast-fed infants.

OBJECTIVE: To analyze the characteristics of infants and children diagnosed with nutritional rickets at two medical centers in North Carolina in the 1990s. STUDY DESIGN: The physical and radiographic findings, calcium, phosphorus, alkaline phosphatase, and 25-hydroxyvitamin D levels of infants and children diagnosed with nutritional rickets at two medical centers were reviewed. Breast-feeding data were obtained from the North Carolina Women, Infants and Children Program (WIC). RESULTS: Thirty patients with nutritional rickets were first seen between 1990 and June of 1999. Over half of the cases occurred in 1998 and the first half of 1999. All patients were African American children who were breast fed without receiving supplemental vitamin D. The average duration of breast-feeding was 12.5 months. The age at diagnosis was 5 to 25 months, with a median age of 15.5 months. Growth failure was common: length was <5th percentile in 65% of cases, and weight was <5th percentile in 43%. CONCLUSION: Factors that may have contributed to the increase in referrals of children with nutritional rickets include more African American women breast-feeding, fewer infants receiving vitamin D supplements, and mothers and children exposed to less sunlight. We recommend that all dark-skinned breast-fed infants and children receive vitamin D supplementation.

A sensitive solid-phase fluoroimmunoassay for detection of opiates in urine.

An automated flow fluorometer designed for kinetic binding analysis was adapted to develop a solid-phase competitive fluoroimmunoassay for urinalysis of opiates. The solid phase consisted of polymer beads coated with commercial monoclonal antibodies (MAbs) raised against morphine. Fluorescein-conjugated morphine (FL-MOR) was used as the fluorescein-labeled hapten. The dissociation equilibrium constant (K(D)) for the binding of FL-MOR to the anti-MOR MAb was 0.23 nM. The binding of FL-MOR to the anti-MOR MAb reached steady state within minutes and was displaced effectively by morphine and other opiates. Morphine-3-glucuronide (M3G), the major urinary metabolite of heroin and morphine, competed effectively with FL-MOR in a concentration-dependent manner for binding to the antimorphine MAb and was therefore used to construct the calibration curve. The sensitivity of the assay was 0.2 ng/mL for M3G. The assay was effective at concentrations of M3G from 0.2 to 50 ng/mL, with an IC50 of 2 ng/mL. Other opiates and heroin metabolites that showed >50% crossreactivity when present at 1 microg/mL included codeine, morphine-6-glucuronide, and oxycodone. Methadone showed very low crossreactivity (<5%), which is a benefit for testing in patients being treated for opiate addictions. The high sensitivity of the assay and the relatively high cutoff value for positive opiate tests allows very small sample volumes (e.g., in saliva or sweat) to be analyzed. A double-blind comparison using 205 clinical urine samples showed good agreement between this single-step competitive assay and a commercially performed enzyme multiplied immunoassay technique for the detection of opiates and benzoylecgonine (a metabolite of cocaine).

A 12-year follow-up of a methadone medical maintenance program.

Methadone Medical Maintenance (MDM) is an alternative for treatment of stable methadone maintained individuals. It involves a monthly physician's visit, at which methadone take-home doses are dispensed to last until the next appointment. The safety and efficacy of this treatment modality is currently under investigation. The purpose of this study was to evaluate the long-term safety and efficacy of MDM in a methadone program in Baltimore. A sample of 21 patients was enrolled in the study and followed for 12 years. They were evaluated once a month by a primary care physician affiliated with a methadone clinic who collected urine toxicology samples and dispensed the monthly methadone dose. The results showed that only 6 (28.6%) patients dropped out during the 12 years of the study. Twelve (0.5%) of 2,290 urine samples collected were positive for drugs. No methadone overdose or diversion was observed. Participants reported significant improvement in their quality of life. The results of this study support the safety and efficacy of medical maintenance of stable methadone maintained individuals.

Familial medullary thyroid carcinoma: presymptomatic diagnosis and management in children.

Two kindreds with familial medullary thyroid carcinoma (MTC) are described in which affected family members had variable clinical and pathologic manifestations. Genetic testing in 2 children from one kindred revealed a mutation in exon 10, codon 618 (TGC to AGC) in the extracellular cysteine-rich region of the RET gene. In this kindred an 11-year-old had microscopic evidence of MTC; however, a 17-year-old had no evidence of pathology on thyroidectomy. In a second kindred a rare mutation in exon 14, codon 804 (GTG to TTG) of the intracellular tyrosine kinase region of the RET gene was detected. In this kindred MTC has occurred in the 4th to 5th decades of life, with a clinical spectrum in mutation-positive family members ranging from no disease and C-cell hyperplasia to carcinoma with lymph node metastasis; a 7-year-old with the mutation and a normal response to provocative testing was also identified. Management recommendations in children from families with clearly defined familial MTC may be individualized to reflect emerging genotype-phenotype correlations.

Hypocalcemic tetany in a toddler with undiagnosed rickets.

A 17-month-old black girl presented to the pediatric emergency department with sudden onset of her hands and feet "drawing up." A diagnosis of vitamin D deficiency rickets with tetany was made on a history of exclusive breast-feeding, low serum calcium, phosphorus, and 25-hydroxyvitamin D levels, and bone radiographs. Nutritional rickets should be considered in the differential diagnosis of acute hypocalcemia.

Assessment of an automated solid phase competitive fluoroimmunoassay for benzoylecgonine in untreated urine.

A new solid phase fluoroimmunoassay using a fully automated flow fluorometer adapted for urinalysis of drug metabolites is described. Fluorescein-conjugated benzoylecgonine (FL-BE) and monoclonal antibodies (mAb) against benzoylecgonine (BE) were the reagents used for demonstration. The solid phase consisted of anti-BE mAbs immobilized on the surface of polymethyl methacrylate (PMMA) beads. Free BE in solution competed with FL-BE and reduced bead-bound fluorescence in a concentration-dependent manner. The binding of FL-BE to the anti-BE mAb reached steady-state within minutes. FL-BE was not bound by uncoated beads nor beads coated with non-specific proteins or IgG. The signal-to-noise ratio was 33, and the sensitivity of the assay was 2 ng ml(-1) for BE. The effective concentration of BE was 1 to 100 ng ml(-1), with an IC50 value of 12 ng ml(-1). The mAb showed equal affinities for BE, cocaine, and cocaethylene, but a five order-of-magnitude lower affinity for ecgonine and ecgonine methylester. In a double-blind comparison using clinical urine samples, the data from this single-step competitive assay had excellent agreement with results obtained using a fiber-optic biosensor (FOB), and the EMIT assay performed commercially. The assay provided kinetic data rapidly and can be used to detect small analytes for which antibodies and fluorescein conjugates are available. The affinity of the mAb for FL-BE, calculated from kinetic analysis of the time course of the on and off reaction, was 2.25 x 10(-9) M.

The relationship between parental history and substance use severity in drug treatment patients.

The authors explored the relationship between the history of parental problematic alcohol and drug use and their adult children's alcohol and drug use disorders. Subjects were 347 admissions to an outpatient substance abuse program. There was a positive relationship between the number of parents affected by alcohol and/or drug problems and the percentage of probands with co-existing alcohol and drug use disorders for probands with alcohol use disorders but not for those with only drug abuse. Probands with two affected parents had significantly higher alcohol abuse scores and drug, family, and psychiatric composite test scores than those with a negative family history. This preliminary study indicates that the severity of a proband's substance use disorder may be influenced by parental substance use history.

Suicidal ideation and behavior and noncompliance with the medical regimen among diabetic adolescents.

OBJECTIVE: To examine (1) the 1-year and lifetime prevalence of suicidal thoughts and behavior among adolescents with insulin-dependent diabetes mellitus (IDDM), (2) the relationship between suicidal thoughts and serious noncompliance with the medical regimen, and (3) factors including psychiatric disorder, self-efficacy expectations, and hopelessness that might mediate the relationship between suicidal thoughts and noncompliance. METHOD: Semistructured and structured interview instruments and self-report questionnaires were used to determine history of suicidal thoughts and behavior, serious noncompliance with the medical regimen, current psychiatric disorder, hopelessness, and self-efficacy expectations among 91 adolescents attending outpatient clinic appointments. RESULTS: The rate of suicidal ideation among the diabetic adolescents was higher than expected, but the rate of suicide attempts was comparable with that reported for the general population. Suicidal thoughts were strongly associated with serious noncompliance with the medical regimen. Duration of IDDM and psychiatric diagnosis were related to both suicidal ideation within the previous year and lifetime suicidal ideation. Diagnosable psychiatric disorder and not living in a two-parent home were related to noncompliance with medical treatment. CONCLUSIONS: Suicidal thoughts and serious noncompliance with the medical regimen are strongly associated among diabetic teenagers, and psychiatric disorder is a common correlate of both.