Lynn E. Sullivan

Effect of restricting dietary protein on the progression of renal failure in patients with insulin-dependent diabetes mellitus

BACKGROUND Restriction of dietary protein may slow the progression of renal failure in diverse renal diseases, but the extent to which such a diet is beneficial in patients with diabetic nephropathy is uncertain. METHODS We studied the effect of reduced intake of protein and phosphorus on the progression of renal disease in 35 patients with insulin-dependent (Type I) diabetes mellitus and clinically evident nephropathy. The low-protein, low-phosphorus diet contained 0.6 g of protein per kilogram of ideal body weight per day, 500 to 1000 mg of phosphorus, and 2000 mg of sodium. The control diet consisted of the patients prestudy diet with the stipulation that it contain 2000 mg of sodium and at least 1 g of protein per kilogram per day and 1000 mg of phosphorus. Renal function was assessed by measurement of iothalamate and creatinine clearances at intervals of 3 to 6 months, and the patients were followed for a minimum of 12 months (mean, 34.7). The declines in mean glomerular filtration rates were compared between groups by linear-regression analysis of the glomerular filtration rate as a function of time. RESULTS The patients who followed the study diet for a mean of 37.1 months had declines in iothalamate clearance of 0.0043 ml per second per month and in creatinine clearance of 0.0055 ml per second per month. The comparable values in the control group were 0.0168 and 0.0135, respectively (P less than 0.05). Blood pressure was well controlled, and the degree of glycemic control was comparable in both groups. CONCLUSION Dietary restriction of protein and phosphorus can retard the progression of renal failure in patients with Type I diabetes mellitus who have nephropathy. We believe that wider use of this treatment is indicated.

Hiv Treatment Outcomes Among Hiv-infected, Opioid-dependent Patients Receiving Buprenorphine/naloxone Treatment within Hiv Clinical Care Settings: Results From a Multisite Study

Background:Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes. Methods:HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome. Results:At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (β = 1.34 [1.18, 1.53]) and achieve viral suppression (β = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (β = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (β = 0.55 [0.35, 0.97]), homeless (β = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (β = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (β = 10.27 [5.79, 18.23]). Female gender (β = 1.91 [1.07, 3.41]), Hispanic ethnicity (β = 2.82 [1.44, 5.49]), and increased general health quality of life (β = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time. Conclusions:Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality-of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population.

Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review.

Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area.

Long-Term Treatment with Buprenorphine/Naloxone in Primary Care: Results at 2-5 Years

To examine long-term outcomes with primary care office-based buprenorphine/naloxone treatment, we followed 53 opioid-dependent patients who had already demonstrated six months of documented clinical stability for 2-5 years. Primary outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases, and adverse events. Thirty-eight percent of enrolled subjects were retained for two years. Ninety-one percent of urine samples had no evidence of opioid use, and patient satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment occurred. We conclude that select opioid-dependent patients exhibit moderate levels of retention in primary care office-based treatment.

Factors affecting willingness to provide buprenorphine treatment

Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit time; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine.

Integrating Buprenorphine Treatment into Office-based Practice: a Qualitative Study

BACKGROUNDDespite the availability and demonstrated effectiveness of office-based buprenorphine maintenance treatment (BMT), the systematic examination of physicians’ attitudes towards this new medical practice has been largely neglected.OBJECTIVETo identify facilitators and barriers to the potential or actual implementation of BMT by office-based medical providers.DESIGNQualitative study using individual and group semi-structured interviews.PARTICIPANTSTwenty-three practicing office-based physicians in New England.APPROACHInterviews were audiotaped, transcribed, and entered into a qualitative software program. The transcripts were thematically coded using the constant comparative method by a multidisciplinary team.RESULTSEighty percent of the physicians were white; 55% were women. The mean number of years since graduating medical school was 14 (SD = 10). The primary areas of clinical specialization were internal medicine (50%), infectious disease (20%), and addiction medicine (15%). Physicians identified physician, patient, and logistical factors that would either facilitate or serve as a barrier to their integration of BMT into clinical practice. Physician facilitators included promoting continuity of patient care, positive perceptions of BMT, and viewing BMT as a positive alternative to methadone maintenance. Physician barriers included competing activities, lack of interest, and lack of expertise in addiction treatment. Physicians’ perceptions of patient-related barriers included concerns about confidentiality and cost, and low motivation for treatment. Perceived logistical barriers included lack of remuneration for BMT, limited ancillary support for physicians, not enough time, and a perceived low prevalence of opioid dependence in physicians’ practices.CONCLUSIONSAddressing physicians’ perceptions of facilitators and barriers to BMT is crucial to supporting the further expansion of BMT into primary care and office-based practices.

A Randomized Trial of Cognitive Behavioral Therapy in Primary Care-based Buprenorphine

OBJECTIVE To determine the impact of cognitive behavioral therapy on outcomes in primary care, office-based buprenorphine/naloxone treatment of opioid dependence. METHODS We conducted a 24-week randomized clinical trial in 141 opioid-dependent patients in a primary care clinic. Patients were randomized to physician management or physician management plus cognitive behavioral therapy. Physician management was brief, manual guided, and medically focused; cognitive behavioral therapy was manual guided and provided for the first 12 weeks of treatment. The primary outcome measures were self-reported frequency of illicit opioid use and the maximum number of consecutive weeks of abstinence from illicit opioids, as documented by urine toxicology and self-report. RESULTS The 2 treatments had similar effectiveness with respect to reduction in the mean self-reported frequency of opioid use, from 5.3 days per week (95% confidence interval, 5.1-5.5) at baseline to 0.4 (95% confidence interval, 0.1-0.6) for the second half of maintenance (P<.001 for the comparisons of induction and maintenance with baseline), with no differences between the 2 groups (P=.96) or between the treatments over time (P=.44). For the maximum consecutive weeks of opioid abstinence there was a significant main effect of time (P<.001), but the interaction (P=.11) and main effect of group (P=.84) were not significant. No differences were observed on the basis of treatment assignment with respect to cocaine use or study completion. CONCLUSIONS Among patients receiving buprenorphine/naloxone in primary care for opioid dependence, the effectiveness of physician management did not differ significantly from that of physician management plus cognitive behavioral therapy.

A Meta-analysis of the Efficacy of Nonphysician Brief Interventions for Unhealthy Alcohol Use: Implications for the Patient-Centered Medical Home

Brief physician interventions can reduce alcohol consumption. Physicians may not have the time to provide brief interventions, and it is unclear whether nonphysicians can do so effectively. We conducted a systematic review and meta-analysis to examine the efficacy of brief interventions by nonphysician clinicians for unhealthy alcohol use. We searched the English-language literature in MEDLINE and other databases covering the domains of alcohol problems, primary care, nonphysician, and brief interventions. Studies of brief interventions delivered at least in part by nonphysicians in primary care and examining drinking outcomes were included. Sensitivity analyses examined the effect of excluding studies that contributed disproportionately to the heterogeneity of results. Thirteen studies, conducted 1996-2008, met our criteria. Seven studies with a total of 2,633 patients were included in the meta-analysis. Nonphysician interventions were associated with 1.7 (95% confidence interval [CI]=-.03 to -3.5) fewer standard drinks per week than control conditions (p = .054). Excluding the one study that increased heterogeneity, the effect was smaller but reached statistical significance; nonphysician counseling was associated with 1.4 (95% CI = .3- 2.4) fewer standard drinks per week compared to control (p = .012). Nonphysician brief interventions are modestly effective at reducing drinking in primary care patients with unhealthy alcohol use.

The potential role of buprenorphine in the treatment of opioid dependence in HIV-infected individuals and in HIV infection prevention.

Untreated opioid dependence is a major obstacle to the successful treatment and prevention of human immunodeficiency virus (HIV) infection. In this review, we examine the interwoven epidemics of HIV infection and opioid dependence and the emerging role of buprenorphine in improving HIV treatment outcomes among infected individuals, as well as its role in primary and secondary prevention. This article addresses some of the emerging issues about integrating buprenorphine treatment into HIV clinical care settings and the various strategies that must be considered. Specifically, it addresses the role of buprenorphine in improving HIV treatment outcomes through engagement in care, access to antiretroviral therapy and preventive therapies for opportunistic infections, and the potential benefits of and pitfalls in integrating buprenorphine into HIV clinical care settings. We discuss the key research questions regarding buprenorphine in the area of improving HIV treatment outcomes and prevention, including a review of published studies of buprenorphine and antiretroviral treatment and currently ongoing studies, and provide insight into and models for integrating buprenorphine into HIV clinical care settings. Dialogue among practitioners and policy makers in the HIV care and substance abuse communities will facilitate an effective expansion of buprenorphine and ensure that these beneficial outcomes are achieved.

Buprenorphine: Its Role in Preventing HIV Transmission and Improving the Care of HIV-Infected Patients with Opioid Dependence

In the United States, approximately 25% of the 40,000 new human immunodeficiency virus (HIV) infections each year are secondary to injection drug use. Worldwide, there are an estimated 12.6 million injection drug users, and 10% of HIV infections (420,000 infections in 2003) are associated with this practice. Buprenorphine is a new medication used to treat opioid dependence that shows promise for reducing the rate of HIV transmission and improving the care of opioid-dependent patients with HIV infection. Although buprenorphine faces fewer clinical and regulatory barriers than does methadone, the optimal strategy for integration of office-based treatment of opioid dependence and HIV disease is an area of ongoing research. This review addresses the introduction of buprenorphine, in terms of public health, policy, and clinical implications for HIV-infected patients and for HIV care providers.