Barriers to opioid use disorder treatment among people who use drugs in the rural United States: A qualitative, multi-site study.

BACKGROUND: In 2020, 2.8 million people required substance use disorder (SUD) treatment in nonmetropolitan or 'rural' areas in the U.S. Among this population, only 10% received SUD treatment from a specialty facility, and 1 in 500 received medication for opioid use disorder (MOUD). We explored the context surrounding barriers to SUD treatment in the rural United States. METHODS: We conducted semi-structured, in-depth interviews from 2018 to 2019 to assess barriers to SUD treatment among people who use drugs (PWUD) across seven rural U.S. study sites. Using the social-ecological model (SEM), we examined individual, interpersonal, organizational, community, and policy factors contributing to perceived barriers to SUD treatment. We employed deductive and inductive coding and analytical approaches to identify themes. We also calculated descriptive statistics for participant characteristics and salient themes. RESULTS: Among 304 participants (55% male, mean age 36 years), we identified barriers to SUD treatment in rural areas across SEM levels. At the individual/interpersonal level, relevant themes included: fear of withdrawal, the need to "get things in order" before entering treatment, close-knit communities and limited confidentiality, networks and settings that perpetuated drug use, and stigma. Organizational-level barriers included: strict facility rules, treatment programs managed like corrections facilities, lack of gender-specific treatment programs, and concerns about jeopardizing employment. Community-level barriers included: limited availability of treatment in local rural communities, long distances and limited transportation, waitlists, and a lack of information about treatment options. Policy-level themes included insurance challenges and system-imposed barriers such as arrest and incarceration. CONCLUSION: Our findings highlight multi-level barriers to SUD treatment in rural U.S. communities. Salient barriers included the need to travel long distances to treatment, challenges to confidentiality due to small, close-knit communities where people are highly familiar with one another, and high-threshold treatment program practices. Our findings point to the need to facilitate the elimination of treatment barriers at each level of the SEM in rural America.

Barriers to retention in inpatient and residential drug treatment among persons who use opioids and/or injection drugs living in the rural U.S.

AIM: Barriers to retention in inpatient and residential care for persons who use drugs are understudied in the rural context. We sought to better understand barriers to retention in inpatient and residential drug treatment in a large, multi-site, geographically diverse sample of persons who use opioids and/or injection drugs in the rural U.S. METHODS: We conducted semi-structured individual interviews with persons currently using opioids and/or injection drugs in 9 U.S. states, including Illinois, Kentucky, Massachusetts, North Carolina, New Hampshire, Ohio, Oregon, Vermont, and Wisconsin. Content areas included substance use history and experiences with all modalities of drug treatment. We performed initial structural coding followed by an iterative "open-coding" process of itemizing and categorizing content within each code, and a multi-coder memoing process to summarize themes. We identified themes using three levels of the Social-Ecological Model (SEM): individual, interpersonal, and facility-level (organizational) barriers. RESULTS: Among 304 interviewed, over half (n = 166, 54 %) reported having experienced inpatient and residential treatment. Lack of treatment retention was driven by interrelated factors at all levels of the SEM. Person-level factors inhibiting retention included lack of readiness to stop using, which was particularly true for court-ordered treatment, and dislike of "freedom limitations". The sole interpersonal-level factor was the influence of other patients on re-initiation of drug use. Facility-level barriers included unaddressed withdrawal symptoms and lack of access to MOUD, staff relatability, inadequate staff training, and, particularly in residential treatment, lack of structure and supervision. Lack of preparation for coping with real-world triggers was seen as a barrier to engagement in ongoing treatment. CONCLUSION: Barriers to retention in inpatient and residential substance use treatment were present at three levels of the SEM. Interviews suggest much room for improvement in inpatient and residential drug treatment programs with respect to improving access to MOUD, tailoring content to better address social challenges in the rural context, and improving quality control measures with respect to staff and resident supervision.

Pre-exposure prophylaxis awareness, acceptability and potential stigma among medical and non-medical clinic staff in methadone treatment settings in northern New Jersey: The key role of non-medical staff in enhancing HIV prevention.

BACKGROUND: HIV prevention is needed among people who use drugs (PWUD) due to mixing sex and drugs, selling/trading sex, and/or injecting drugs. Pre-exposure prophylaxis (PrEP) is an extremely effective biomedical HIV prevention strategy, but uptake remains low among communities most in need of HIV prevention, including PWUD. Previous studies have found that providers are less willing to prescribe PrEP to PWUD, yet PWUD express high levels of PrEP acceptance. More research is needed to understand how people who provide substance use treatment services think about PrEP to maximize this biomedical prevention strategy. METHODS: The study conducted semistructured interviews with 29 staff members in two methadone clinic settings in urban northern New Jersey. Staff members included medical providers, methadone counselors, intake coordinators, front desk staff, lab technicians, security guards, and administrative/leadership personnel. RESULTS: All staff recognized the need for HIV prevention among their patient populations, but most were either unaware of PrEP or unfamiliar with its purpose and how it works. Medical providers were more likely to have some PrEP knowledge in comparison to counselors and other staff, but the former largely did not have in-depth knowledge. Among those familiar with PrEP, many confused PrEP with HIV medication, as Truvada was the only FDA-approved PrEP at the time of the study. About half of participants expressed clear support for PrEP, while the other half expressed mixed or negative attitudes related to HIV, sexual behavior, and mistrust of the medication. Both the positive and negative perceptions entailed stigmatizing elements. RECOMMENDATIONS: Due to patients' frequent interactions with non-medical staff (e.g., front desk staff, lab technicians, etc.), all staff, not only medical personnel, should be aware of PrEP and comfortable discussing it to foster well-informed, nonjudgmental conversations about HIV prevention with patients. PrEP education should specifically address HIV and sexual-related stigma, as even positive perceptions of PrEP may entail stigmatizing elements.

Synthesis and antimalarial activity of sixteen dispiro-1,2,4, 5-tetraoxanes: alkyl-substituted 7,8,15,16-tetraoxadispiro[5.2.5. 2]hexadecanes.

Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15, 16-tetraoxadispiro[5.2.5.2]hexadecanes) were synthesized to explore dispiro-1,2,4,5-tetraoxane SAR and to identify tetraoxanes with better oral antimalarial activity than prototype tetraoxane 1 (WR 148999). The tetraoxanes were prepared either by peroxidation of the corresponding cyclohexanone derivatives in H(2)SO(4)/CH(3)CN or by ozonolysis of the corresponding cyclohexanone methyl oximes. Those tetraoxanes with alkyl substituents at the 1 and 10 positions were formed as single stereoisomers, whereas the five tetraoxanes formed without the stereochemical control provided by alkyl groups at the 1 and 10 positions were isolated as mixtures of diastereomers. Three of the sixteen tetraoxanes were inactive (IC(50)'s > 1000 nM), but five (2, 6, 10, 11, 12) had IC(50)'s between 10 and 30 nM against the chloroquine-sensitive D6 and chloroquine-resistant W2 clones of Plasmodium falciparum compared to corresponding IC(50)'s of 55 and 32 nM for 1 and 8.4 and 7.3 nM for artemisinin. We suggest that tetraoxanes 13, 16, and 17 were inactive and tetraoxanes 4 and 7 were weakly active due to steric effects preventing or hindering peroxide bond access to parasite heme. Tetraoxanes 1, 10, 11, and 14, along with artemisinin and arteether as controls, were administered po b.i.d. (128 mg/kg/day) to P. berghei-infected mice on days 3, 4, and 5 post-infection. At this dose, tetraoxanes 10, 11, and 14 cured between 40% and 60% of the infected animals. In comparison, artemisinin and tetraoxane 1 produced no cures, whereas arteether cured 100% of the infected animals. There was no apparent relationship between tetraoxane structure and in vitro neurotoxicity, nor was there any correlation between antimalarial activity and neurotoxicity for these seventeen tetraoxanes.

THE RELATION BETWEEN THE BRITISH AND THE EUROPEAN FLORAS.

The paper presents a brief and personal history of the main developments in British vascular plant taxonomy and distribution studies in a European setting since the Second World War. It assesses the importance of the'European view', and considers recent and current work under two main heads: the factual information itself, and the presentation of the facts, especially in the form of dot distribution maps.

THE NAME OF THE ROSE: A REVIEW OF IDEAS ON THE EUROPEAN BIAS IN ANGIOSPERM CLASSIFICATION.

This 'Tansley Review' paper takes as its starting point a paper of mine published in 1961, which explored the shape and size of modern Angiosperm families and genera as a product of taxonomic practice over centuries. It considers how far the conclusion - that our existing scientific classification, based on Linnaeus' masterly standardization in the eighteenth century, is very markedly 'Eurocentric'- has been criticized, accepted or modified by subsequent writers. In particular, it assesses the important contribution made in recent years by ethnobiologists using expert knowledge from social anthropology, linguistics and other disciplines. Finally, the paper considers briefly the broader aspects of current controversies about the nature and purpose of taxonomic activity, including the argument about its relevance to evolutionary knowledge and speculation. It concludes that, to a remarkable degree, practising taxonomists ignore conceptual or philosophical difficulties and are able to co-operate, although their leisurely and arcane procedures may not measure up to the'information explosion'. Contents Summary 527 I. Introduction 528 II. The age and size of Angiosperm families and genera 530 III. Recognition of the European bias in classification 539 IV. Conclusions 542 References 544.

Influence of pH on hydrolytic decomposition of diethylpropion hydrochloride: stability studies on drug substance and tablets using high-performance liquid chromatography.

The influence of pH on the hydrolysis of diethylpropion hydrochloride was investigated. Hydrolytic decomposition of the drug in solution at 45 degrees occurred at a very slow and constant rate at pH 3.5 and below but increased rapidly as the pH was raised above 3.5. Results of stability studies performed on six commercial tablet products from five manufacturers showed a similar relationship between the decomposition rate and the formulation pH. A reaction pathway based on the formation of an enamine structure is proposed for the pH-dependent hydrolysis. A high-performance liquid chromatographic assay for the drug is presented, which also separates and detects the hydrolysis product 1-phenyl-1,2-propanedione and the compound assumed to be the enol tautomer of this product.

High-performance liquid chromatographic determination of diethylpropion hydrochloride in tablets: isolation and identification of two decomposition products.

A rapid assay was developed for diethylpropion hydrochloride tablets using high-performance liquid chromatography (HPLC) with UV detection. This technique provided separation of the drug from other UV-absorbing components present as the result of decomposition. A major decomposition product detected by HPLC in extracts of tablets and of the cotton filler from a tablet bottle was collected from the column effluents. This product was subsequently identified as 1-phenyl-1,2-propanedione, a highly volatile compound. A second decomposition product, isolated from decomposed drug by distillation from alkaline solution, was identified as diethylamine, apparently present as the hydrochloride salt, GLC, UV, IR, NMR, and mass spectrometry were used to confirm the identity of the decomposition products. HPLC assay results compared favorably with results of the NF assay; the latter procedure separated the drug from 1-phenyl-1,2-propanedione via liquid-liquid extraction.

Determination of diphenoxylate hydrochloride and atropine sulfate in solutions and tablets.

Methods for the determination of diphenoxylate hydrochloride and atropine sulfate combinations in solutions and powdered tablet composites are presented. A semiautomated assay for diphenoxylate hydrochloride in individual tablets (content uniformity) also is presented. The USP XIX assays for these products are cumbersome and, in the case of solutions, inaccurate due to spectral interferences; the proposed methods offer substantial improvements in sensitivity, specificity, and speed. Results obtained by the USP and proposed methods are compared for several lots of commercial products. The accuracy and precision of the proposed methods are shown by standard recovery studies.

Multicolumn solid-phase extraction cleanup of organophosphorus and organochlorine pesticide residues in vegetable oils and butterfat.

Diatomaceous earth columns used with reversed and normal solid phase extraction (SPE) cartridges were evaluated for the quantitative determination of a number of organophosphorus (OP) and organochlorine (OC) pesticide residues in edible vegetable oils and butterfat. An oil or fat sample (about 2 g) in hexane was passed through a diatomaceous earth (Extrelut QE) column and a C18 bonded silica (ODS) SPE cartridge, resulting in the separation of the pesticides from about 98% of the lipids. The eluate was split in half, with the first portion concentrated into acetone for the determination of OP pesticides by gas chromatography with flame photometric detection (GC-FPD). The other half was passed through an Alumina-N SPE cartridge for additional cleanup of lipid matrix to determine OC pesticides by GC with electron-capture detection (GC-ECD). Average recoveries from fortified samples were greater than 89% for the pesticides studied.

TCDD residues in fish and shellfish from U.S. waterways.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in the edible portion of fish and shellfish from various U.S. waterways has been monitored since 1979. Analytical results for the period 1979-1994 are reported. Extracts obtained after column chromatographic and liquid chromatographic cleanup were examined by electron capture detection-gas chromatography (GC), and final quantitation and confirmation were performed by GC/mass spectrometry with multiple ion detection. Analyses of 1623 test samples indicated that TCDD residues in fish and shellfish were not widespread but rather were localized in areas near waste sites, chlorophenol manufacturers, and pulp and paper mills. Analytical results indicated that levels in aquatic species from these sites have been declining steadily. No TCDD (limit of detection and confirmation, 1-2 ppt) has been found in recent years in aquatic species from most Atlantic, Pacific, and Gulf of Mexico sites and Great Lakes other than Lake Ontario and Saginaw Bay (Lake Huron).

Determination of chlorthalidone and clonidine hydrochloride in tablets by HPLC.

A rapid, reversed-phase high performance liquid chromatographic method is described for the determination of chlorthalidone and clonidine hydrochloride combinations in tablets. Individual tablets or composite samples were sonicated in water, diluted with methanol, and filtered prior to chromatographing. Chlorthalidone, formulated at 15 mg/tablet, was chromatographed on octadecylsilyl-bonded, 5 to 6-micrometers, spherical silica with 50% methanol in water mobile phase. Clonidine hydrochloride, formulated at 0.1 or 0.2 mg/tablet, was chromatographed on trimethylsilyl-bonded, 5 to 6-micrometers, spherical silica with 65% methanol in pH 7.9 phosphate buffer mobile phase. Both were determined with a spectrophotometric detector at 254 nm. Mean recoveries of the drugs from six synthetic tablet samples were 100.3% for chlorthalidone and 99.7% for clonidine hydrochloride (at 0.1 mg/tablet level) with coefficients of variation of 0.79 and 1.55%, respectively.

Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides.

Bacterial lipopolysaccharide (LPS) release during periodontal infection is a significant component of periodontal disease. We hypothesized that some bacterial LPS release results from bacterial exposure to antibiotics. Therefore, we examined the ability of various classes of antibiotics to induce LPS release from Porphyromonas gingivalis as well as the ability of antimicrobial peptides (AMPs) to inhibit purified LPS. All antibiotics tested against P. gingivalis were able to liberate 1.9-12.9 times more LPS as compared to untreated bacteria. Among the three AMPs tested, LL-37 was found to be the most potent inhibitor of cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6) production and completely neutralized purified P. ginigivalis LPS activity in the chromogenic limulus amebocyte lysate (LAL) and whole blood cytokine stimulation assays. These observations suggest that therapeutic approaches utilizing AMPs as adjuncts to neutralize released LPS should be considered.

Preliminary evaluation of high-performance liquid chromatography with photoconductivity detection for the determination of selected pesticides as potential food contaminants.

The applicability of the Tracor Model 965 photoconductivity detector to the determination of a variety of pesticide chemicals, particularly polar and/or thermally labile compounds which are troublesome in gas chromatographic analysis, has been investigated. The effects of various operating parameters (e.g., mobile phase composition, flow-rate and irradiation wavelength) on signal-to-noise output for selected compounds have been evaluated. A comparison of photoconductivity responses with those obtained from a UV detector connected in tandem was made for selected reference standards and food sample extracts. The photoconductivity detector was found to be suitable for the determination of pesticide residues at sub-parts-per-million levels. The linearity and reproducibility of response are adequate for practical quantitative applications.

Determination of captan, folpet, and captafol in fruits and vegetables, using two multiresidue methods.

Two multiresidue methods, the Mills method and the Luke et al. method, are widely used for the determination of pesticides in foods. These methods were evaluated for the determination of the fungicides captan, folpet, and captafol in selected fruits and vegetables. The analytical behavior of standards through these methods was investigated first. Recoveries from apples, strawberries, lettuce, and tomatoes fortified with these compounds at levels of 0.2-5.9 ppm were then obtained. The analytes were quantitated by gas chromatography with electron capture detection, using a column of 5% SP-2401 on 100-120 mesh Supelcoport. Recoveries of captan, folpet, and captafol from fortified crops ranged from 69 to 78, 90 to 93, and 67 to 83%, respectively, by the Mills procedure and from 87 to 102, 81 to 106, and 91 to 109%, respectively, by the Luke et al. method modified to include additional solvent elution of the optional Florisil column.

Alumina blending technique for separation of pesticides from lipids.

An evaluation of an extraction technique for elimination of lipids during pesticide residue analysis was undertaken, which included a study of the parameters involved in an attempt to optimize the separation and recovery of selected pesticides from lipid samples. The choice of alumina, the degree of water deactivation of alumina, the amount of alumina relative to the weight of sample taken, the volume and composition of extraction solvent, the blending time, and the filtration procedure were all significant factors. Optimization of these factors resulted in greater than 90% recoveries of selected chlorinated pesticides from fortified fatty samples. In addition, the amount of co-extracted lipid material was about one-third of that obtained with the official method (AOAC 29.014), and less analytical time was required for the extraction by the proposed technique. The formation of troublesome emulsions sometimes encountered with the official method was also eliminated.

Ion-pairing liquid chromatographic determination of benzimidazole fungicides in foods.

A method is described for determining residues in foods of thiabendazole, thiophanate methyl, the di-oxygen analogue metabolite [dimethyl 4,4'-O-phenylene bis (allophanate)] that is the metabolite name of the latter, and methyl-2-benzimidazole carbamate, which is the major metabolite and fungitoxic principle common to both thiophanate methyl and benomyl. The residues are extracted from the product using methanol and are partitioned into dichloromethane after initial acidification and again after subsequent alkalinization of the extract. Residues are separated and quantified by reverse-phase liquid chromatography using an ion-pairing mobile phase with UV and fluorescence detectors in tandem. Recoveries from 7 different food crops fortified at 0.2-35 ppm levels ranged from 64 to 105%.