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Background: Conversion to a belatacept-based immunosuppression is currently used as a calcineurin inhibitor (CNI) avoidance strategy when the CNI-based standard-of-care immunosuppression is not tolerated after kidney transplantation. However, there is a lack of evidence on the long-term benefit and safety after conversion to belatacept., Methods: We prospectively enrolled 311 kidney transplant recipients from 2007 to 2020 from two referral centers, converted from CNI to belatacept after transplant according to a prespecified protocol. Patients were matched at the time of conversion to patients maintained with CNIs, using optimal matching. The primary end point was death-censored allograft survival at 7 years. The secondary end points were patient survival, eGFR, and safety outcomes, including serious viral infections, immune-related complications, antibody-mediated rejection, T-cell-mediated rejection, de novo anti-HLA donor-specific antibody, de novo diabetes, cardiovascular events, and oncologic complications., Results: A total of 243 patients converted to belatacept (belatacept group) were matched to 243 patients maintained on CNIs (CNI control group). All recipient, transplant, functional, histologic, and immunologic parameters were well balanced between the two groups with a standardized mean difference below 0.05. At 7 years post-conversion to belatacept, allograft survival was 78% compared with 63% in the CNI control group ( P < 0.001 for log-rank test). The safety outcomes showed a similar rate of patient death (28% in the belatacept group versus 36% in the CNI control group), active antibody-mediated rejection (6% versus 7%), T-cell-mediated rejection (4% versus 4%), major adverse cardiovascular events, and cancer occurrence (9% versus 11%). A significantly higher rate of de novo proteinuria was observed in the belatacept group as compared with the CNI control group (37% versus 21%, P < 0.001)., Conclusions: This real-world evidence study shows that conversion to belatacept post-transplant was associated with lower risk of graft failure and acceptable safety outcomes compared with patients maintained on CNIs., Clinical Trial Registry Name and Registration Number: Long-term Outcomes after Conversion to Belatacept, NCT04733131 ., (Copyright © 2024 by the American Society of Nephrology.)

The 2019 coronavirus disease (COVID-19) infection had newly emerged with predominant respiratory complications. Other extrapulmonary features had been recently described. Here, we describe a COVID-19 patient presenting with multiorgan involvement mimicking systemic lupus erythematosus. He was successfully treated with glucocorticoids and tocilizumab.

Background: Short-term mechanical ventilation (MV) protects against sepsis-induced diaphragmatic dysfunction. Prolonged MV induces diaphragmatic dysfunction in non-septic animals, but few reports describe the effects of prolonged MV in sepsis. We hypothesized that prolonged MV is not protective but worsens the diaphragmatic dysfunction induced by a mild sepsis, because MV and sepsis share key signaling mechanisms, such as cytokine upregulation., Method: We studied the impact of prolonged MV (12 h) in four groups (n = 8) of male Wistar rats: 1) endotoxemia induced by intraperitoneal injection of Escherichia coli lipopolysaccharide, 2) MV without endotoxemia, 3) combination of endotoxemia and MV and 4) sham control. Diaphragm mechanical performance, pro-inflammatory cytokine concentrations (Tumor Necrosis Factor-α, Interleukin-1β, Interleukin-6) in plasma were measured., Results: Prolonged MV and sepsis independtly reduced maximum diaphragm force (-27%, P = 0.003; -37%, P<0.001; respectively). MV and sepsis acted additively to further decrease diaphragm force (-62%, P<0.001). Similar results were observed for diaphragm kinetics (maximum lengthening velocity -47%, P<0.001). Sepsis and MV reduced diaphragm cross sectional area of type I and IIx fibers, which was further increased by the combination of sepsis and MV (all P<0.05). Sepsis and MV were individually associated with the presence of a robust perimysial inflammatory infiltrate, which was more marked when sepsis and MV were both present (all P<0.05). Sepsis and, to a lesser extent, MV increased proinflammatory cytokine production in plasma and diaphragm (all P<0.05); proinflammatory cytokine expression in plasma was increased further by the combination of sepsis and MV (all P<0.05). Maximum diaphragm force correlated negatively with plasma and diaphragmatic cytokine production (all p<0.05)., Conclusions: Prolonged (12 h) MV exacerbated sepsis-induced decrease in diaphragm performance. Systemic and diaphragmatic overproduction of pro-inflammatory cytokines may contribute to diaphragm weakness., Competing Interests: Alexandre Demoule reports personal fees from Maquet, grants, personal fees and non-financial support from Covidien, personal fees from MSD, grants and non-financial support from Philips, non-financial support from Drager, grants and personal fees from Resmed, personal fees from fisher & Paykel, all outside the submitted work. This does not alter his adherence to PLOS ONE policies on sharing data and materials. The other authors declare no competing interest.

Background: Gastroparesis is a complex clinical entity; many aspects of which remain unknown. Although most patients have idiopathic, diabetic, or postsurgical gastroparesis, many are thought to have measurable neuromuscular abnormalities. Immunotherapy has recently been utilized to treat suspected autoimmune gastrointestinal dysmotility., Methods: Fourteen patients with symptoms of gastroparesis (Gp) who were refractory to drug/device were selected from 443 Gp patients from 2013 to 2015 who were treated at the University of Louisville motility center. All patients underwent a structural and psychiatric evaluation along with detailed psychological and behavioral examination to rule out eating disorders. We performed detailed neuromuscular evaluation and all 14 patients received at least 12 weeks of intravenous immunoglobulin (400 mg/kg infusion weekly). Response was defined subjectively (symptomatic improvement) using standardized IDIOM score system., Key Results: All 14 patients had serological evidence and/or tissue evidence of immunological abnormality. Post-IVIG therapy, there was a significant improvement in symptoms scores for nausea, vomiting, early satiety, and abdominal pain., Conclusions and Inferences: Although limited by the absence of placebo group, the data illustrate the role of autoimmunity and neuromuscular evaluation in patients with gastroparesis and support the utility of a diagnostic trial of immunotherapy in an effort to improve therapeutic outcomes for such patients., (© 2017 John Wiley & Sons Ltd.)

Purpose of Review: The purpose of this paper is to review the epidemiology of obesity and the evolution of artificial sweeteners; to examine the latest research on the effects of artificial sweeteners on the host microbiome, the gut-brain axis, glucose homeostasis, and energy consumption; and to discuss how all of these changes ultimately contribute to obesity., Recent Findings: Although artificial sweeteners were developed as a sugar substitute to help reduce insulin resistance and obesity, data in both animal models and humans suggest that the effects of artificial sweeteners may contribute to metabolic syndrome and the obesity epidemic. Artificial sweeteners appear to change the host microbiome, lead to decreased satiety, and alter glucose homeostasis, and are associated with increased caloric consumption and weight gain. Artificial sweeteners are marketed as a healthy alternative to sugar and as a tool for weight loss. Data however suggests that the intended effects do not correlate with what is seen in clinical practice. Future research should focus on the newer plant-based sweeteners, incorporate extended study durations to determine the long-term effects of artificial sweetener consumption, and focus on changes in the microbiome, as that seems to be one of the main driving forces behind nutrient absorption and glucose metabolism.

Purpose of Review: The purpose of this paper is to review the epidemiology of obesity and the most recent literature on popular fad diets and exercise regimens that are used for weight loss. The weight loss plans that will be discussed in this article include juicing or detoxification diets, intermittent fasting, the paleo diet, and high intensity training., Recent Findings: Despite the growing popularity of fad diets and exercise plans for weight loss, there are limited studies that actually suggest these particular regimens are beneficial and lead to long-term weight loss. Juicing or detoxification diets tend to work because they lead to extremely low caloric intake for short periods of time, however tend to lead to weight gain once a normal diet is resumed. Both intermittent fasting and the paleo diet lead to weight loss because of overall decreased caloric intake as well. Lastly, studies on short bursts of high intensity training have shown remarkable weight loss and improvements in cardiovascular health. Review of the literature does suggest that some fad diets and exercise plans do lead to weight loss; however, the studies are quite limited and are all based on the concept of caloric restriction.

Purpose: The standard evaluation of multisystem Langerhans cell histiocytosis (LCH) includes a clinical evaluation, laboratory tests and a skeleton/skull X-ray survey, with chest high-resolution computed tomography (HRCT) in the case of pulmonary involvement. Preliminary reports suggest that 18 F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET-CT) may be useful for evaluating patients with LCH., Methods: Fourteen consecutive adult patients with multisystem LCH were included in this retrospective study, and were evaluated using standard procedures and 18 F-FDG PET-CT. The two sets of findings were compared both at baseline and during follow-up. Serial HRCT and pulmonary function tests were used to evaluate outcome in patients with lung involvement., Results: At the baseline evaluation, PET-CT identified every LCH localization found with the standard evaluation (except a mild cecum infiltration). PET-CT showed additional lesions in seven patients, mostly involving bones, and differentiated inactive from active lesions. Thyroid 18 F-FDG uptake was identified in three cases. No pituitary stalk 18 F-FDG uptake was observed in patients with pituitary LCH. Only 3/12 (25 %) patients with pulmonary LCH displayed moderate pulmonary 18 F-FDG uptake. During follow-up, variations (≥50 % of maximum standardized uptake) in bone 18 F-FDG uptake intensity were correlated with disease state and response to treatment. The absence of lung 18 F-FDG uptake did not preclude lung function improvement after treatment., Conclusions: Except for cases with pulmonary and pituitary involvement, 18 F-FDG PET-CT could replace the standard evaluation for staging of adult patients with multisystem LCH. Serial PET-CT scans are useful for evaluating treatment responses, particularly in cases with bone LCH involvement.

Interstitial lung disease (ILD) is a common form of extramuscular involvement in patients with polymyositis/dermatomyositis and is associated with poor prognosis. This study was designed to describe the long-term outcome of myositis-associated ILD. This retrospective observational study was conducted in 48 consecutive patients. Two groups defined according to outcome were compared to determine prognostic factors: a "severe" group (vital capacity [VC] < 50 % or carbon monoxide transfer factor [TLCO] < 35 % or death or lung transplantation) and a "nonsevere" group (other patients). The study population comprised 31 women and 17 men with a median age of 49.5 ± 13.6 years. Mean PFT results at the onset of ILD were 56.9 ± 23.1 % pred. for VC and 42.1 ± 16.6 % pred. for TLCO. Median (range) follow-up was 65 (2-204) months. Three patients (6.4 %) died. At last follow-up, 19 patients were classified in the "severe" group and 27 patients were classified in the "nonsevere" group. Two patients lost to follow-up after less than 12 months were excluded from this analysis. Multivariate analysis identified two independent prognostic factors: VC at onset of ILD [OR 0.95 (95 % CI 0.90-0.99)] and myopathic changes on electromyography [OR 5.76 (95 % CI 1.10-30.3)]. Patients treated in our pulmonology department for myositis-associated ILD had severe initial PFT results but a low mortality rate. Independent prognostic factors at presentation were initial VC and myopathic changes on electromyography. This study highlights the need for studies focusing on the correlation between muscle and lung pathogenic mechanisms.

Purpose. The association between transarterial chemoembolization- (TACE-) induced HCC tumor necrosis measured by the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and patient survival is poorly defined. We hypothesize that survival will be superior in HCC patients with increased TACE-induced tumor necrosis. Materials and Methods. TACE interventions were retrospectively reviewed. Tumor response was quantified via dichotomized (responders and nonresponders) and the four defined mRECIST categories. Results. Median survival following TACE was significantly greater in responders compared to nonresponders (20.8 months versus 14.9 months, p = 0.011). Survival outcomes also significantly varied among the four mRECIST categories (p = 0.0003): complete, 21.4 months; partial, 20.8; stable, 16.8; and progressive, 7.73. Only progressive disease demonstrated significantly worse survival when compared to complete response. Multivariable analysis showed that progressive disease, increasing total tumor diameter, and non-Child-Pugh class A were independent predictors of post-TACE mortality. Conclusions. Both dichotomized (responders and nonresponders) and the four defined mRECIST responses to TACE in patients with HCC were predictive of survival. The main driver of the survival analysis was poor survival in the progressive disease group. Surprisingly, there was small nonsignificant survival benefit between complete, partial, and stable disease groups. These findings may inform HCC treatment decisions following first TACE.

DNA-damaging drugs induce a plethora of molecular and cellular alterations in tumor cells, but their interrelationship is largely obscure. Here, we show that carboplatin treatment of human ovarian carcinoma SKOV3 cells triggers an ordered sequence of events, which precedes the emergence of mitotic chemoresistant cells. The initial phase of cell death after initiation of carboplatin treatment is followed around day 14 by the emergence of a mixed cell population consisting of cycling, cell cycle-arrested and senescent cells. At this stage, giant cells make up >80% of the cell population, p21 (CDKN1A) in strongly induced, and cell numbers remain nearly static. Subsequently, cell death decreases, p21 expression drops to a low level and cell divisions increase, including regular mitoses of giant cells and depolyploidization by multi-daughter divisions. These events are accompanied by the upregulation of stemness markers and a pro-inflammatory secretory phenotype, peaking after approximately 14 days of treatment. At the same time the cells initiate epithelial to mesenchymal transition, which over the subsequent weeks continuously increases, concomitantly with the emergence of highly proliferative, migratory, dedifferentiated, pro-inflammatory and chemoresistant cells (SKOV3-R). These cells are anchorage-independent and grow in a 3D collagen matrix, while cells on day 14 do not survive under these conditions, indicating that SKOV3-R cells were generated thereafter by the multi-stage process described above. This process was essentially recapitulated with the ovarian carcinoma cell line IGROV-1. Our observations suggest that transitory cells characterized by polyploidy, features of stemness and a pro-inflammatory secretory phenotype contribute to the acquisition of chemoresistance.

Pulmonary Langerhans cell histiocytosis is a rare diffuse cystic interstitial pneumonia of unknown etiology that occurs selectively in young smokers of both genders. The multicenter studies conducted by the reference center have better defined the short and medium terms natural history of the disease and the clinical management of patients. A substantial proportion of patients experience a dramatic decline in their lung function soon after diagnosis. Importantly, smoking cessation is associated with a decreased risk of subsequent deterioration. Cladribine, a purine analogue, chemotherapy may dramatically improve lung function in patients with progressive pulmonary Langerhans cell histiocytosis, but this treatment should be used only in the setting of clinical research. Specific pulmonary hypertension therapies (anti-endothelin receptors, inhibitors of phosphodiesterases) may be used with caution in specialized centres for patients with severe pulmonary hypertension, and seem to be well tolerated. The recent identification of the V600E mutation of the BRAF oncogene in approximately half of the Langerhans cell histiocytosis lesions, including pulmonary granulomas, represents an important step forward in the understanding of the pathogenesis of Langerhans cell histiocytosis. Potentially it opens the way to targeted therapies., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Besides its established functions in intermediary metabolism and developmental processes, the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has a less defined role in tumorigenesis. In the present study, we have identified a function for PPARβ/δ in cancer cell invasion. We show that two structurally divergent inhibitory ligands for PPARβ/δ, the inverse agonists ST247 and DG172, strongly inhibit the serum- and transforming growth factor β (TGFβ)-induced invasion of MDA-MB-231 human breast cancer cells into a three-dimensional matrigel matrix. To elucidate the molecular basis of this finding, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) and microarray analyses, which identified the gene encoding angiopoietin-like 4 (ANGPTL4) as the major transcriptional PPARβ/δ target in MDA-MB-231 cells, previously implicated in TGFβ-mediated tumor progression and metastatic dissemination. We show that the induction of ANGPTL4 by TGFβ and other oncogenic signals is strongly repressed by ST247 and DG172 in a PPARβ/δ-dependent fashion, resulting in the inhibition of ANGPTL4 secretion. This effect is attributable to these ligands' ability to induce a dominant transcriptional repressor complex at the site of transcription initiation that blocks preinitiation complex formation through an histone deacetylase-independent, non-canonical mechanism. Repression of ANGPTL4 transcription by inverse PPARβ/δ agonists is functionally linked to the inhibition of cancer cell invasion into a three-dimensional matrix, as (i) invasion of MDA-MB-231 cells is critically dependent on ANGPTL4 expression, (ii) recombinant ANGPTL4 stimulates invasion, and (iii) reverses the inhibitory effect of ST247 and DG172. These findings indicate that a PPARβ/δ-ANGPTL4 pathway is involved in the regulation of tumor cell invasion and that its pharmacological manipulation by inverse PPARβ/δ agonists is feasible.

Pneumococci are responsible for lower respiratory tract infections (bronchitis and pneumonia) and invasive infections (bacteremia and meningitis). Pneumococcal vaccination is recommended for adults at high risk of pneumococcal infection. Asthma is not currently considered as an indication for pneumococcal vaccination and this vaccination is indicated only in case of respiratory insufficiency. Indeed, asthma is not usually considered as a risk factor for pneumococcal infection and pneumococcal polysaccharide vaccine does not decrease mortality in patients presenting with COPD. According to several recent epidemiological studies, asthma is associated with a doubled risk of pneumonia and invasive infections. This epidemiological association is supported by biological data suggesting increased susceptibility to pneumococcal infection in asthmatic patients. Pneumococci are responsible for 10 to 15% of acute exacerbations and onset of often-severe pneumonia in patients presenting with COPD. The recent availability of pneumococcal conjugate vaccines could be interesting for these patients, but their clinical and cost effectiveness will have to be demonstrated before they can be recommended for these conditions., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The purpose of this research (N = 160) was to describe and compare substance abuse treatment in two programs under managed care: one residential (RT) and one outpatient (OP). Clients in both settings improved significantly from before to after treatment in relation to substance use and quality of life. However, intensity of treatment (hours of care/week) was much greater in RT and days of sobriety were significantly higher after treatment in RT than in OP (p = .04). Intensity was negatively related to incidents of substance use during treatment (SUdT), which predicted substance use after treatment; SUdT averaged .2 for RT, and 1.6 for OP (p = .0001). Importantly, treatment was completed by 74 patients (over 90%) from RT, with 8 dropping out, and 53 (almost 70%) of those in OP completed treatment while 25 dropped out. Intensity, as seen in the RT program, rather than duration, was more effective in substance use reduction and treatment completion.

Context: Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence are efficacious in improving outcomes in substance abusers, but these treatments have rarely been implemented in community-based settings., Objective: To evaluate the efficacy of an abstinence-based contingency management intervention as an addition to usual care in community treatment settings., Design: Random assignment to usual care or usual care plus abstinence-based incentives for 12 weeks., Setting: Eight community-based outpatient psychosocial drug abuse treatment programs., Participants: A total of 415 cocaine or methamphetamine users beginning outpatient substance abuse treatment., Intervention: All participants received standard care, and those assigned to the abstinence-based incentive condition also earned chances to win prizes for submitting substance-free urine samples; the chances of winning prizes increased with continuous time abstinent., Main Outcome Measures: Retention, counseling attendance, total number of substance-free samples provided, percentage of stimulant- and alcohol-free samples submitted, and longest duration of confirmed stimulant abstinence., Results: Participants assigned to the abstinence-based incentive condition remained in treatment for a mean +/- SD of 8.0 +/- 4.2 weeks and attended a mean +/- SD of 19.2 +/- 16.8 counseling sessions compared with 6.9 +/- 4.4 weeks and 15.7 +/- 14.4 sessions for those assigned to the usual care condition (P<.02 for all). Participants in the abstinence-based incentive condition also submitted significantly more stimulant- and alcohol-free samples (P<.001). The abstinence-based incentive group was significantly more likely to achieve 4, 8, and 12 weeks of continuous abstinence than the control group, with odds ratios of 2.5, 2.7, and 4.5, respectively. However, the percentage of positive samples submitted was low overall and did not differ between conditions., Conclusion: The abstinence-based incentive procedure, which provided a mean of 203 dollars in prizes per participant, was efficacious in improving retention and associated abstinence outcomes.

Aims: The Center for Substance Abuse Treatment (CSAT) Methamphetamine Treatment Project (MTP) is the largest randomized clinical trial of treatments for methamphetamine (MA) dependence to date. The objective of the study was to compare the Matrix Model, a manualized treatment method, with treatment-as-usual (TAU) in eight community out-patient settings in the Western United States., Design: Over an 18-month period between 1999 and 2001, 978 treatment-seeking, MA-dependent people were randomly assigned to receive either TAU at each site or a manualized 16-week treatment (Matrix Model)., Setting: The study was conducted as an eight-site out-patient trial, with six sites located in California and one each in Montana and Hawaii., Findings: In the overall sample, and in the majority of sites, those who were assigned to Matrix treatment attended more clinical sessions, stayed in treatment longer, provided more MA-free urine samples during the treatment period and had longer periods of MA abstinence than those assigned to receive TAU. Measures of drug use and functioning collected at treatment discharge and 6 months post-admission indicate significant improvement by participants in all sites and conditions when compared to baseline levels, but the superiority of the Matrix approach did not persist at these two timepoints., Conclusions: Study results demonstrate a significant initial step in documenting the efficacy of the Matrix approach. Although the superiority of the Matrix approach over TAU was not maintained at the post-treatment timepoints, the in-treatment benefit is an important demonstration of empirical support for this psychosocial treatment approach.

Increasing numbers of methamphetamine users sought treatment during the decade of the 1990s. Little is known about the post treatment status of methamphetamine users who enter treatment. The data presented in this paper describe the outcome status of a group of a convenience sample of 114 methamphetamine users from a total group of 500 methamphetamine users who were treated 2-5 years prior to a follow up interview. Since the sample was not randomly selected, no specific treatment outcome attribution is possible. Methamphetamine use and other drug use of the follow up sample was substantially reduced from pretreatment levels. In general, the follow up status of the sample was much improved as compared to before treatment. However, headaches and depression were reported at a similar rate at follow up as had been reported at treatment admission.

Methamphetamine (MA) abuse has been a problem in the western United States for decades. However, recently the incidence of MA abuse has risen to epidemic levels in some regions and among particular subgroups of the population. Recognizing the need to develop effective treatments for MA dependence, the Center for Substance Abuse Treatment (CSAT) established a multisite Methamphetamine Treatment Program (MTP) that compares the Matrix Model treatment program for MA to the treatments as usual at seven community-based clinics in California, Montana and Hawaii. Examination of the clients receiving services though this project provides an opportunity to explore particular issues of diverse special populations who are impacted by the problem of MA dependence. These groups include rural Americans, Native Americans, Hawaiians, gay and bisexual males and drug court participants. Specifically, this article examines cultural, geographic and situational barriers to accessing and completing treatment and presents strategies that have been used to overcome these barriers.

Providers and their treatment programs are the focus of efforts to translate research into practice. In the best of partnerships, they are more than the recipients of research efforts, because they are actively involved in developing and evaluating healthy links between practice and research . This article reports on experiences in a multisite methamphetamine treatment trial funded in October of 1998 by the Center for Substance Abuse Treatment. The goal of the trial is to generate knowledge about how a comprehensive treatment protocol developed by the Matrix Center in Los Angeles can be effectively transferred to the community drug treatment system. The Matrix model provides a three-times-per-week outpatient treatment experience that combines behavioral, educational, and 12-Step counseling techniques. When complete, the study will compare outcomes of the 16-week Matrix program with the usual treatment offered by the programs at the eight participating sites. The UCLA Drug Abuse Research Center and the Matrix Institute on Addictions coordinate the trial. This article describes factors that have fostered or hindered the development of this partnership. These factors can be divided into three temporal phases, although the circumstances presented may occur at any time during the research process. The first set of factors affecting the development of a healthy research-to-practice relationship exists prior to the establishment of that relationship. A second set of circumstances occurs at the initiation of the collaborative enterprise, and the third set of factors is more involved in the development and maintenance of ongoing productive collaboration between researchers and providers.

The use of methamphetamine and cocaine have both produced significant public health problems during the past two decades. Although these powerful psychostimulants have many common acute and chronic effects, there are some important differences in who uses these drugs and the consequences of their use. This article reports on two large cohorts of treatment-seeking cocaine and methamphetamine users who entered treatment at the same facility over the same four-year period of time. Patterns of use differed significantly. Cocaine users have more episodic use patterns, spend more money on purchasing their drugs, and use alcohol more heavily. Methamphetamine users include a higher proportion of women, more frequently use on a daily basis, use marijuana more often, and experience more severe medical and psychiatric consequences. Despite the differences in the stimulant drug effects and consequences, the treatment response to a multicomponent, outpatient program is very similar.

Outpatient treatment of 42 patients who presented with dependence upon prescription opioids was attempted by two different methods. The first group of 21 patients was treated by 21-day detoxification followed by psychotherapeutic counseling (D/C), and the next 21 patients were offered 21-day detoxification to be followed by opioid maintenance if detoxification was unsuccessful (D/M). Only 5 of 21 (23.8%) patients in the D/C group compared to 20 of 21 (95.2%) in the D/M group completed three weeks of treatment (P less than .001). On admission, no patient perceived that chronic pain due to a medical condition would be an impediment to withdrawal from opioids, but pain which was masked by opioid dependency and which emerged during detoxification proved to be an insurmountable barrier to total withdrawal in the majority of patients. Treatment of outpatients who presented with dependence upon prescription opioids was best provided in the study by opioid maintenance and adjunctive pain therapy.