Successful Taper Research Articles

Avacopan in the treatment of refractory scleritis secondary to granulomatosis with polyangiitis: A case report.

Avacopan is a novel C5a receptor inhibitor which was recently licensed for treatment of severe granulomatosis with polyangiitis (GPA) in the European Union and the United Kingdom. To the best of our knowledge, this is the first described case on initial ophthalmic outcomes in a patient with severe GPA and concurrent refractory scleritis treated with avacopan. We present a case of de novo scleritis in a 77-year-old male with a background of retinitis pigmentosa with Argus II implant in situ. Severe scleral inflammation occurred following a suture removal from the implant site. Remission was not maintained despite orbital floor injections and high dose oral prednisolone. The diagnostic work-up revealed GPA which quickly progressed to involve vital organs. In view of his systemic deterioration, he was started on avacopan alongside rituximab, cyclophosphamide and high dose oral prednisolone. Sustained remission of scleritis was noted after 7 months of treatment with avacopan and low dose oral prednisolone with no other maintenance immunosuppression. We observed a sustained benefit of avacopan in allowing for successful taper of systemic steroids. We report that avacopan used alongside other immunosuppressants may be a viable option in patients with GPA and concurrent refractory scleritis. Further studies are needed to establish the longer term impact of this agent on the control of scleral inflammation.

Opioid characteristics and nonopioid interventions associated with successful opioid taper in patients with chronic noncancer pain.

Current research indicates that tapering opioids may improve pain and function in patients with chronic noncancer pain. However, gaps in the literature remain regarding the choice of opioid and nonopioid interventions to support a successful taper. This study used an Australian primary care data set to identify a cohort of patients on long-term opioid therapy commencing opioid taper between January 2016 and September 2019. Using logistic regression analysis, we compared key clinical factors associated with differing taper outcomes. Of a total of 3371 patients who commenced taper, 1068 (31.7%) completed taper within 12 months. In the 3 months after commencement of taper, compared with those who did not complete taper, patients who successfully completed opioid taper were less likely to be prescribed buprenorphine (odds ratio [OR] 0.691; 95% CI: 0.530-0.901), fentanyl (OR, 0.429; 95% CI: 0.295-0.622), and long-acting (LA) opioids, including methadone (OR, 0.349; 95% CI: 0.157-0.774), oxycodone-naloxone (OR, 0.521; 95% CI: 0.407-0.669), and LA tapentadol (OR, 0.645; 95% CI: 0.461-0.902), but more likely to be prescribed codeine (OR, 1.308; 95% CI: 1.036-1.652). Compared with those who did not complete taper, patients who successfully tapered were less likely to be prescribed any formulations of oxycodone (short-acting [SA]: OR, 0.533; 95% CI: 0.422-0.672, LA: OR, 0.356; 95% CI: 0.240-0.530) and tramadol (SA: OR, 0.370; 95% CI: 0.218-0.628, LA: OR, 0.317; 95% CI: 0.234-0.428). The type of opioid prescribed in the months after commencement of taper seems to influence the taper outcomes. These findings may inform prospective studies on opioid taper.

Retrospective, Multi-Center Analysis of Ruxolitinib Tapering after Successful Treatment of Steroid Refractory Chronic Graft Versus Host Disease

Introduction: Ruxolitinib (RUX) has been approved for 2 nd line therapy or beyond for steroid-refractory chronic graft-versus-host disease (cGVHD) based on the REACH3 study demonstrating superior efficacy of RUX with respect to greater overall response and failure-free survival (FFS) vs. best available therapies. Despite this, there is no real-world data to evaluate whether the tapering speed used in this study is clinically relevant, or results in successful RUX taper without flare. Accordingly, the present retrospective, multi-center study provides data on RUX tapering in patients who had been successfully treated with RUX for steroid-refractory cGVHD. Patients and Methods: 109 patients treated with RUX to treat chronic GVHD at 4 Canadian transplant centers (Toronto, Calgary, Saskatoon, Quebec City) were enrolled, with patient characteristics in Table 1. The overall response was defined as complete (CR) or partial response (PR) as defined by the 2014 NIH consensus criteria. RUX tapering was started at the treating physician's discretion, while maintaining CR, PR or no change (NC) after complete tapering of steroid. When cGVHD flare is noted during gradual RUX tapering, RUX dose was escalated back to the previous dose level based on physician's discretion. FFS after RUX tapering (R-FFS) was calculated from RUX taper day 1 until either GVHD flare or death from any cause. For risk factor analysis of GVHD flare-up, Cox's proportional hazard model was applied for R-FFS at 24 months. Results: Of 109 patients enrolled, 70 attempted RUX tapering at median 12.9 months (95% CI [8.9-16.4 months]) following start of RUX therapy after achievement of CR (n=29), PR (n=28) or NC (n=22) with complete discontinuation of steroid in 16 (23%). Daily RUX dose at the time of RUX taper was 30mg (n=4, 5%), 20mg (n=59, 79%), 15mg (n=4, 5%), and 10mg (n=8, 11%). Time from start of RUX taper to daily RUX dose of 20mg, 15mg, 10mg and complete discontinuation was 8 ± 6 days, 81 ± 23 days, 185 ± 38 days, and 204 ± 30 days, respectively. In terms of RUX tapering speed, RUX dose was reduced, on average, by 5mg/day every 41 days. With a median follow up duration of 12 months in those who attempted RUX taper, 22 (31%) experienced a cGVHD flare at a median 19.4 months after RUX tapering attempt, while 41 pts (59%) were able to wean RUX completely and 7 pts (13%) remained on tapering schedule. Median time to successful taper was 6.8 months (range 4.6-73.7 months). The median R-FFS for RUX taper (95% confidence interval [CI]) to flare was 4.2 years (2.1 - 6.3), while estimated R-FFS at 1 year was 89.1% (0.785 - 0.947%) and at 3 years was 56.0% (39.4-69.7%). Univariate analysis showed that duration of RUX ≥ 434 days prior to taper was associated with lower risk of R-FFS (Hazard ratio [HR] 0.323, 95% C.I. [0.095 - 1.093]), while non-matched related donor was associated with higher risk of R-FFS with HR of 2.826 (1.011 - 7.902). However, multivariate analysis could not confirm these findings. There were 9 deaths during RUX taper, including sepsis (n=3), cardiac arrest (n=1), COVID pneumonia (n=1), leukoencephalopathy (n=1) and undetermined causes (n=3), which were not directly related to RUX taper. Conclusions: Our study provides real-world data that (1) RUX can be successfully tapered with no associated GVHD flare at 12 months median follow up in a majority of this patient population, (2) faster tapering (by 5mg every 6 weeks) demonstrates comparable efficacy to 5mg every 8 weeks (as per REACH3) and (3) factors such as GVHD severity, number of GVHD organ involvement or CR achievement prior to taper were not associated with R-FFS.

Tapering Recommendations for Benzodiazepines

Tapering Recommendations for Benzodiazepines

Impact of Voluntary Opioid Taper Program in Cancer Survivors (FR460B)

•Identify the challenges and risks related to long-term opioid therapy in cancer patients.•Characterize a successful voluntary opioid taper program in an outpatient palliative care clinic. ASCO Clinical Practice Guidelines for the management of chronic pain in cancer survivors recommend reducing or discontinuing opioids when no longer warranted, although if and how this can be achieved in practice is unknown. We examined the feasibility, impact, and best practices of a voluntary outpatient opioid taper program in cancer survivors on long-term opioid therapy (LTOT) for chronic pain. Eligible patients were followed in an NCI-designated Comprehensive Cancer Center. A retrospective chart review using electronic medical records was conducted in patients whose opioid dose was tapered between October 1, 2013, and April 30, 2018. Demographics, clinical data, and detailed pain regimens were collected. Statistical analyses were conducted to characterize the time from taper initiation to the lowest achieved dose, and to explore the relationships between dose reduction and independent variables. Opioid dose reduction was achieved in 162 (82%) out of 196 patients offered a voluntary taper. 119 (74%) of patients who were tapered had equal or greater than a 50% dose reduction. The average pain scores at baseline and at the time of the lowest tapered dose were unchanged. Less than 10% of patients reported withdrawal symptoms. An initial opioid dose of > 500 oral morphine equivalents at baseline was an independent predictor of a smaller percentage of taper. The presence of a co-morbid psychiatric condition and adjuvant co-analgesics did not significantly affect the amount of the taper. A clinically meaningful and well-tolerated opioid taper is feasible in cancer survivors on LTOT.

S891 SUCCESSFUL TREATMENT OF INTESTINAL GRAFT‐VERSUS‐HOST DISEASE WITH FECAL MICROBIOTA TRANSPLANTATION

Background:Disruption of the intestinal microbiome has a negative influence on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). Decreased gut flora diversity with loss of commensals and pathobiont domination, is associated with an increased risk to develop graft‐versus‐host disease (GvHD). Fecal microbiota transplantation (FMT) has successfully been used to treat Clostridium difficile enteritis but the safety and efficacy of FMT in immunocompromised GvHD patients remains to be elucidated.Aims:1. To assess the safety and effectiveness of FMT as treatment for GvHD patients in a prospective, single‐arm pilot study2. To analyze the microbiome dynamics of GvHD patients receiving an FMTMethods:Fifteen patients with steroid‐refractory or steroid‐dependent intestinal GvHD received a single FMT from an unrelated, healthy donor via nasoduodenal infusion. Follow‐up included collection of blood and fecal samples prior to FMT and at 1, 4, 12 and 24 weeks after FMT as well as clinical follow‐up up to 6months.Results:FMT was well tolerated by all patients, there were no serious adverse events observed that could be attributed to FMT. Response evaluation at 4 weeks after FMT identified 11 participants with a complete response (CR), defined as resolution of all GvHD, without other interventions to alleviate symptoms. In 6 CR patients, the normalization of stool frequency and consistency was sustained throughout the whole period of follow‐up, with successful taper of immunosuppressants. Five other responders initially showed improvement of GvHD after FMT but relapsed upon prednisolone taper (CR/sf; complete responders with secondary failure). A durable response to FMT was associated with a better prognosis (Figure 1). Analysis of peripheral blood immune cell subsets did not reveal significant differences. Alpha diversity of fecal samples, analyzed by 16S ribosomal RNA sequencing, was low in patients pre‐FMT but improved upon response to treatment in CR and CR/sf patients. One week after FMT, the fecal microbial composition of CR patients resembled that of the donor the most, suggesting a better engraftment of fecal donor species in patients with persistent responses.Summary/Conclusion:This pilot study shows the potential of donor FMT to safely restore microbial diversity and improve symptoms of steroid‐refractory or steroid‐dependent GvHD patients. These encouraging data promote further investigation of this therapy in larger cohorts.image

Topical timolol as adjunct therapy to shorten oral propranolol therapy for infantile hemangiomas.

First-line therapy for infantile hemangiomas (IH) is oral propranolol, a systemic beta-blocker with the risk of rare but serious adverse effects. Topical timolol presents an attractive off-label alternative with good tolerability, but sequential therapy with propranolol followed by timolol is not well studied. Here, we report effects of topical timolol preceding or following oral propranolol as adjunct therapy for IH. A retrospective chart review of 559 patients with IH seen at the pediatric dermatology clinic of a tertiary care center between December 2008 and January 2018. Children were grouped by treatment received: propranolol only, timolol only, propranolol to timolol, timolol to propranolol to timolol, and timolol to propranolol. Patient demographics, clinical/treatment characteristics, and pairwise differences were explored between groups. Among all patients treated with propranolol, those who received propranolol followed by timolol received the shortest duration of oral propranolol and were the youngest at the time of propranolol completion. These patients received propranolol for a median of 2.2months duration (P=0.006) and were a median of 1.7months younger (P=0.007) compared with patients who received oral propranolol only. None had treatment failure defined as requiring propranolol reinitiation, compared with 13% of patients in the propranolol only group (P=0.036). Sequential therapy with oral propranolol followed by topical timolol for IH may help minimize potential adverse effects of systemic beta-blockers by reducing the duration of propranolol therapy and facilitating successful taper at a younger age without an increase in treatment failures.

Primary Gastrointestinal Histoplasmosis and Vedolizumab

A 38 year old Caucasian male diagnosed with severe ileo-colonic Crohn's disease (complicated with an ileo-cecal valve stricture) 20 years ago presented with abdominal pain, diarrhea and weight loss for 3 months. Mesalamine therapy at initial diagnosis and a subsequent trial of infliximab, adalimumab and natalizumab failed to induce remission. A disease flare persisted with endoscopic evidence of moderate to severe inflammation along the terminal ileum(TI) and entire colon(edema, erythema, friability, granularity,ulcerations and pseudopolyps). Remission was achieved with Vedolizumab and oral prednisone 40mg with a successful taper down to only 25mg daily due to symptoms recurrence. He reported less frequent, less bloody and more formed stools on the regimen. Pertinent medical history includes Clostridium difficile infection(CDI) 2 months after starting vedolizumab that failed oral vancomycin therapy but resolved with fidaxomycin. A surveillance colonoscopy a year after intiating vedolizumab revealed similar findings as mentioned above with significant improvement in endosocopic appearance (pseudopolyps, scarring surrounded by normal mucosa) and microscopic inflammation (architectural distortion, inflammatory cells in lamina propria). Additionally,3 new multi-lobulated cecal polyps too large to be removed endoscopically were biopsied as dysplasia was of concern. Pathology confirmed Histoplasma and he began therapy with Itraconazole for primary gastrointestinal Histoplasmosis(GIH) in the absence of systemic infection with reported improvement in symptoms on reevaluation at 3 months.His diarrhea is at his baseline of 6 bowel movements a day, without rectal bleeding, abdominal pain or weight loss. He is pending a colonoscopy in 1 month. Histoplasmosis is common among patients taking TNF-α inhibitors with related hospitalizations increasing by 15% per year in the last decade and a mortality rate reported at 20%. While there is evidence that vedolizumab increases risk of CDI and cytomegalovirus colitis, data on risk of fungal infections is lacking. GIH frequently involves the TI and cecum secondary to systemic disease making this case of primary GIH intriguing. Further, presentation as a colonic mass is rare, with 20 cases reported thus far. Treatment involves systemic antifungals. Providers should be vigilant for fungal infections among patients on biologics and take timely steps to diagnose and treat them to reduce resultant morbidity and mortality.Figure 1Figure 2Figure 3

Corrosion of the Head-Stem Taper Junction-Are We on the Verge of an Epidemic?: Review Article.

The modular head taper junction has contributed to the success of total hip arthroplasty (THA) greatly. Taper corrosion and wear problems reported for large and extra-large metal-on-metal bearings as well as for bi-modular THA stems have cast doubt on the benefit of the taper interface. Presently, corrosion problems are being reported for nearly all kinds of artificial hip joints incorporating metal heads, questioning taper connections in general. This study aimed to review the mechanical and electrochemical relationships that may lead to taper corrosion, which have been reported more commonly in recent literature, and to also review the contribution of patient characteristics and surgical techniques involved in taper assembly that may contribute to the problem. The search criteria "(corrosion) AND (hip arthroplasty) AND (taper OR trunnion)" and "(hip arthroplasty) AND ((pseudotumor) OR (pseudo-tumor))" in PubMed and the JAAOS were used for the literature search. In addition, the arthroplasty registers were considered. Most studies acknowledge the multifactorial nature of the problem but concentrate their analysis on taper and implant design aspects, since this is the only factor that can be easily quantified. The sometimes conflicting results in the literature could be due to the fact that the other two decisive factors are not sufficiently considered: the loading situation in the patient and the assembly situation by the surgeon. All three factors together determine the fate of a taper junction in THA. There is no single reason as a main cause for taper corrosion. The combined "outcome" of these three factors has to be in a "safe range" to achieve a successful long-term taper fixation. No, this is not the beginning of an epidemic. It is rather the consequence of disregarding known mechanical and electrochemical relationships, which in combination have recently caused a more frequent occurrence-and mainly reporting-of corrosion issues.

Use of Gabapentin as an Adjunct Agent in the Treatment of Neonatal Abstinence Syndrome: A Case Report

We report the use of Gabapentin (Neurontin), an anticonvulsant and analgesic, as a non-opioid adjunct agent in the treatment of a term newborn infant with neonatal abstinence syndrome (NAS). Initial treatment with methadone to prevent withdrawal symptoms was not fully effective. Despite the addition of clonidine, an alpha-2 agonist, he was still unable to be weaned off opioids. The addition of gabapentin reduced symptoms, allowing for successful taper off methadone, and discharge from the hospital. As a non-opioid agent, gabapentin is a drug with potential for assisting with the difficult task of treating NAS refractory to standard opioid therapy due to its sedative and analgesic properties without any respiratory depression.

Guilain-Barre' Syndrome (GBS) Post Adult Cord Blood Transplantation In a Patient With Chronic Lymphocytic Leukemia (CLL)

Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP) has been reported post related and unrelated allogeneic stem cell transplantation but no such case has been reported post unrelated cord blood transplantation. We hereby present the first case of GBS post double umbilical cord blood transplantation (DUCBT).A 55 year old male with relapsed refractory CLL received DUCBT with two 5/6 matched cord units (antigen level HLA-A, HLA-B and allele level HLA-DRB1) with fludarabine, cytoxan and total body irradiation based reduced intensity conditioning regimen. Graft versus host disease (GVHD) prophylaxis was with cyclosporine and mycophenolate. Early post transplant course was complicated by grade 4 acute GVHD of the gut with a complete resolution with steroid therapy and successful taper of all immunosuppression by day 180. 7 months post transplantation, patient presented with skin rash and tingling in both feet that progressed rapidly to lower extremity paralysis over the course of 2 days. Physical exam showed macula-papular rash affecting his upper extremities, upper chest and back area. Neurologic exam was significant for motor weakness in lower extremities 2/5, plantar flexion and knee flexion 3/5. He had loss of deep tendon reflexes in both lower extremities (Achilles and Patellar) and upper extremities (biceps and triceps).Workup revealed normal blood counts, organ function, vitamin B12, folate, TSH level, free cortisol. Serum electrophoresis and immunfixation was also normal. Magnetic resonance imaging of the central nervous system showed mild neural foramina narrowing at the L4-L5 level. Serology for Lyme disease, Epstein Bar virus (EBV), syphilis, cytomegalo virus (CMV), Hepatitis, HIV, toxoplasma, enterovirus and human herpes virus 6 was negative. Blood tests for autoimmune markers including (anti-nuclear antibody)ANA, acetylcholine esterase and volted calcium channel antibodies were normal. A lumbar puncture was performed and showed a high protein level of 67mg/dl, 1 nucleated cell/mm3 and normal glucose level. Cerebrospinal fluid was negative for oligoclonal bands, West Nile virus, cryptosporidium, HHV6, herpes virus 1 and 2, gram stain and cultures. Nerve conduction studies and needle electormyegraphy was suggestive of acute demyelinating polyneuropathy.Based on the above workup, he was diagnosed with GBS and started on therapy with intravenous immunoglobulin at 0.5gm/kg for 4 days and prednisone 1mg/kg daily for the treatment of GVHD. Etiology of GBS was presumed to be related to GVHD as his workup was negative for campylobacter, HIV and CMV. He improved significantly over the next 4 weeks and became ambulatory without assistance but his weakness symptoms relapsed as his prednisone was tapered. Prednisone was increased again to 1mg/kg and sirolimus was started. Patient was successfully tapered of prednisone and remains fully ambulatory without assistance or evidence of GVHD on single agent sirolimus 13 months post DUCBT.This is the first case of autoimmune demyelinating polyneuropathy post DUCBT with association of GVHD that was managed successfully with a combination of intravenous immunoglobulins, steroids and sirolimus. Disclosures:No relevant conflicts of interest to declare.

Impact of clinical pharmacists' recommendations on a proton pump inhibitor taper protocol in an ambulatory care practice.

Previous studies have demonstrated an association between chronic proton pump inhibitor (PPI) utilization and adverse events such as fractures, infections, hypomagnesemia, and vitamin B12 deficiency. Because patients taking PPIs for an extended period of time are more susceptible to these adverse events, an approach to tapering patients off PPIs is clinically warranted. To evaluate the impact of clinical pharmacists' recommendations to clinicians to decrease PPI use in patients when chronic therapy is not indicated. Clinical pharmacists electronically sent PPI taper recommendations for qualifying patients to primary care providers the day before each patient's appointment. Using insurance claims data, an average pills per month (PPM) count was calculated for the 5-month period prior to initiating the PPI taper as well as for the 5-month period after the date of taper initiation. The PPM count was calculated by dividing the total number of pills a patient received by the total number of days in that period, multiplied by 30. The primary outcome for the study was the change in average PPM count from baseline (pretaper period) to follow-up (posttaper period) and was assessed using a paired t-test. Secondary outcomes included change in total annualized PPI costs to the organization, proportion of patients who began the taper protocol after primary care provider recommendation, and whether baseline characteristics were predictors of successful response. Change in annualized PPI costs to the organization was calculated by multiplying the average unit cost per pill (determined using a weighted average of the average wholesale price of the individual drugs) by the PPM change seen with the primary outcome and by the number of patients included in the study and expressed over the period of a full year. Logistic regression analysis was used to determine whether baseline variables including alcohol and tobacco use, diagnosis related to PPI use, PPI dose, dosing frequency, gender, and length of prior PPI use significantly impacted successful tapering. Average PPM count decreased by 8.7 pills (95% CI: 6.4, 11.1), from 25.6 at baseline (95% CI: 23.1, 28.1) to 16.9 at follow-up (95% CI: 14.3, 19.5; P less than 0.001). For the 117 evaluable patients in the study, there was an annualized PPI cost reduction of $18,151. 37.6% (44/117) of pharmacist-recommended tapers were enacted upon by primary care providers at the patient visit. Baseline patient characteristics were not found to be predictors of a successful taper response. Clinical pharmacist intervention may decrease overutilization of PPIs and associated costs in the primary care setting. While a decrease in PPI use was observed in this study, these findings do not imply improvement in clinically meaningful patient outcomes.

Steroid management in newly diagnosed glioblastoma

Glucocorticoids ameliorate neurologic symptoms in patients with glioblastoma, but their adverse effects limit long-term use. This study sought to identify factors associated with steroid taper success or failure in the early stages of glioblastoma treatment. We retrospectively reviewed steroid prescribing practices from date of surgery until one month following radiotherapy (RT) completion among 85 patients with newly diagnosed glioblastoma who were treated on a prospective clinical trial with RT and temozolomide. Sufficient information on steroid dosing was available in 72 patients included in the final analysis. The mean age was 54 years, and 65 % were men. Thirty-nine percent had a gross-total resection. Fifteen patients (21 %) tolerated steroid taper without requiring dose increase during the study. Men and patients with Karnofsky performance scale 90-100 were more likely to have a successful steroid taper. The most common symptom of taper failure was headache, but the reason for steroid increase differed among the different time intervals examined: worsening neurologic deficit in the early post-operative period, headache and non-focal symptoms during RT, and headache and seizure post-RT. Of the 50 patients in whom steroid use during RT was known, 36 (72 %) underwent dose reduction and of those, 21 (58 %) required an increase. The successful early taper of steroids in glioblastoma was associated with male gender and better functional status. Steroids are often tapered during RT, but there is frequent taper failure with this approach. A prospective trial with standardized steroid dosing regimens would be needed to verify these findings.

A Unique Case of Foreign-Body Associated Orbital Myositis

A 50-year-old woman presented with a 2-week history of diplopia and right-sided orbital pain with eye movement. Examination revealed an edematous, ptotic right upper eyelid with conjunctival hyperemia, proptosis, and significant limitation to upward and downward ductions on the right. MRI was significant for a homogeneously enhancing lesion within the superior rectus muscle. A laboratory evaluation seeking an infectious, inflammatory, or autoimmune process was nonrevealing. A diagnosis of orbital myositis was made, and the patient experienced significant improvement with oral corticosteroids. The patient's symptoms, however, recurred after attempts at a slow taper of the corticosteroids. An orbital biopsy of the lesion revealed fibroadipose tissue containing irregularly shaped yellow-white deposits birefringent under polarized light, suggestive of silica crystals. The patient denied any history of trauma or prior surgery. An intraorbital triamcinolone injection to the superior orbit allowed resolution of symptoms and a successful taper off systemic corticosteroids.

Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: results from a population‐based retrospective cohort study

To identify dose-tapering strategies associated with sustained success following methadone maintenance treatment (MMT). Population-based retrospective cohort study. Linked administrative medication dispensation data from British Columbia, Canada. From 25 545 completed MMT episodes, 14 602 of which initiated a taper, 4183 individuals (accounting for 4917 MMT episodes) from 1996 to 2006 met study inclusion criteria. The primary outcome was sustained successful taper, defined as a daily dose ≤5 mg per day in the final week of the treatment episode and no treatment re-entry, opioid-related hospitalization or mortality within 18 months following episode completion. The overall rate of sustained success was 13% among episodes meeting inclusion criteria (646 of 4917), 4.4% (646 of 14 602) among all episodes initiating a taper and 2.5% (646 of 25 545) among all completed episodes in the data set. The results of our multivariate logistic regression analyses suggested that longer tapers had substantially higher odds of success [12-52 weeks versus <12 weeks: odds ratio (OR): 3.58; 95% confidence interval (CI): 2.76-4.65; >52 weeks versus <12 weeks: OR: 6.68; 95% CI: 5.13-8.70], regardless of how early in the treatment episode the taper was initiated, and a more gradual, stepped tapering schedule, with dose decreases scheduled in only 25-50% of the weeks of the taper, provided the highest odds of sustained success (versus <25%: OR: 1.61; 95% CI: 1.22-2.14). The majority of patients attempting to taper from methadone maintenance treatment will not succeed. Success is enhanced by gradual dose reductions interspersed with periods of stabilization. These results can inform the development of a more refined guideline for future clinical practice.

Pharmacotherapy for pulmonary sarcoidosis: A delphi consensus study

Most issues concerning pharmacotherapy of pulmonary sarcoidosis have not been resolved in clinical trials. The objective was to survey sarcoidosis experts concerning the treatment of pulmonary sarcoidosis and attempt to reach a consensus by these experts using a Delphi method. A 6-item questionnaire was developed. Experts were identified at the Diffuse Lung Disease Network at the annual CHEST meeting in October 2008. Three rounds of questionnaires were presented to the experts. Respondent feedback and supporting literature was incorporated into the questionnaires of subsequent rounds. Experts reached a consensus concerning the following issues: (a) corticosteroids are the initial therapy of choice; (b) initial use of inhaled corticosteroids are not recommended; (c) methotrexate was the preferred second-line drug; (d) 40mg of daily prednisone equivalent was the maximum dose recommended for the treatment of acute pulmonary sarcoidosis; (e) tapering to 10mg of daily prednisone equivalent for chronic pulmonary sarcoidosis was considered a successful taper. The experts could not resolve the following issues: (a) the initial corticosteroid dose for the treatment of acute pulmonary sarcoidosis; (b) the decision and timing of corticosteroid therapy in a patient with mild, Stage 2 pulmonary sarcoidosis. This Delphi study revealed that sarcoidosis experts reached a consensus concerning several aspects of the treatment of pulmonary sarcoidosis; these could be considered as appropriate approaches to therapy. Other issues concerning the therapy of pulmonary sarcoidosis remain unresolved by experts, and are areas where further clinical research could be directed.

Natural History of Severe Ulcerative Colitis in a Community-Based Health Plan

We sought to evaluate long-term outcomes of patients with severe ulcerative colitis (UC) after their first hospitalization for the disease. A cohort of 656 patients hospitalized for UC during 1996 to 2004 was followed up for 9 years through 2004. Time-to-event was estimated using actuarial methods, and the proportions of those under follow-up evaluation who experienced outcomes at month 3, year 1, and year 5 were determined. Outcome measures studied were time to subsequent colectomy, rehospitalization for inflammatory bowel disease, and restarting steroid medication. We also used survival analysis to evaluate whether patient characteristics predicted the risk of rehospitalization and colectomy. Among 656 patients initially hospitalized for severe UC, 20% (N = 129) underwent colectomy during their initial hospitalization. Of the remaining 527, a total of 95% (N = 498) were discharged on a steroid taper. At 1 year after discharge, 29% of those remaining under observation were rehospitalized for UC, and an additional 10% required colectomy. At 1 and 5 years after discharge, 34% and 26% received at least a 90-day supply of steroid in the preceding 9 months. Risk of rehospitalization and colectomy were unrelated to the patient's age, sex, or race/ethnicity. The risk for colectomy in patients hospitalized for the first time with severe UC is 20%. In the 3 months after hospitalization the risk for colectomy is 6%. After that, risks appear to decrease proportionate to the time since initial hospitalization.

Mycophenolate mofetil in dermatomyositis: Is it safe?

The authors report 10 patients with idiopathic dermatomyositis treated with mycophenolate mofetil in combination with corticosteroids. Successful steroid taper without disease relapse was achieved in six patients; however, in three patients, treatment was associated with opportunistic infections, leading to death in one patient. The disproportionately high rate of opportunistic infections in this group is considered.

Steroid Refractory Acute and Chronic Graft Versus Host Disease (GVHD) - Response to Photophoresis+/− Rituximab.

Acute GVHD is an important complication following hematopoeitic stem cell transplantation (HSCT), with significant attendant morbidity and mortality. High dose steroids remain the cornerstone of therapy. Steroid refractory GVHD carries a very poor prognosis. Various therapies are available for steroid refractory acute GVHD, but response is not uniform. Among the less intensive regimens, extracorporeal photopheresis (ECP) and rituximab, a chimeric humanized anti CD 20 monoclonal antibody have been shown to be useful in treating refractory acute and chronic GVHD. We describe 8 patients who developed GVHD following transplantation of HLA-identical stem cells, from siblings in 7 and from an unrelated donor in one. 2 patients had steroid refractory chronic GVHD of the liver, 3 patients had a refractory chronic GVHD of the skin and one had a steroid responsive restrictive pulmonary syndrome. Of the patients with skin GVHD, 2 had chronic scelrodermatous GVHD, which was of 20 years duration in one patient and 8 in the other. 2 patients had acute GVHD of the GI tract. The age range was 21– 53 years. All patients were in complete remission from their primary disease at the time of therapy for GVHD. 3 patients had a diagnosis of acute lymphoblasitc leukemia and 5 acute myeloid leukemia All had failed treatment with high dose steroids and/or tacrolimus and/or cellcept, and, one had also failed ATG therapy. Then therapy for refractory GVHD was initiated with rituximab in 3 patients and with photopheresis in 5. 7 patients received ECP. One patient with refractory chronic GVHD of the liver received rituximab alone in addition of steroids and tacrolimus. The patients with acute GVHD were treated with daily ECP for 10 days and then were weaned down to two procedures every 2 weeks. Patients with chronic GVHD received ECP 2 to 3 times a week for 6 weeks and were subsequently similarly weaned down. In the patients with acute GVHD of the GI tract complete responses occurred at 10 days in one patient and 45 days in the second as determined by complete cessation of diarrhea, cramps and nausea. Both patients with chronic GVHD of the liver achieved normalization of the serum bilirubin by 26 and 38 days after initiation of therapy. All patients tolerated successful taper of steroid therapy. The two patients with sclerodermatous GVHD have shown marked improvement in skin texture and range of motion at the involved joints. The patient with the pulmonary symptoms has shown complete normalization of pulmonary function. 5 patients were at risk of CMV reactivation, but failed to do so. One patient developed BK virus associated hemorrhagic cystitis that required therapy with cidofovir. There were 3 admissions for neutropenic fever, three for pneumonia and one each for gastroenteritis, HSV gingivostomatitis and line related sepsis. Two patients had line related thrombosis. None of the patients had relapse of their disease. 2 of the responders had an ECOG performance status 2, two of 3, one of 4 and four of </= 1 while being treated. All patients demonstrated improvement in functional status. ECP and rituximab is a well tolerated and effective modality for therapy of steroid refractory chronic and acute GVHD in both related and unrelated marrow stem cell transplant recipients.

The long-term outcome of a benzodiazepine discontinuation programme in depressed outpatients

Objective: To assess longitudinally the prescription of psychotropic drugs in depressed patients after they participated in a benzodiazepine discontinuation programme. Methods: Two hundred and thirty depressed patients on chronic benzodiazepine therapy took part in a discontinuation programme conducted in 36 general practices. After 2.3 years (S.D.=0.65, range 0.1–3.6) medical records were reviewed. Results: Follow-up was achieved for 207 (90%) patients. Twenty-five (12%) patients remained benzodiazepine free during the full follow-up period. The majority ( n=181, 87%) was prescribed benzodiazepines at an average of 13 (±14) mg of diazepam equivalents for 537 (±375) days. Fifty-five (74% of 74) of the successfully discontinued patients restarted benzodiazepine therapy. Sixty-eight (33%) patients were prescribed benzodiazepines during the whole follow-up period. Successful taper predicted no or lower subsequent benzodiazepine prescription rates (OR=7.3; 95% CI: 2–16). No influence of GP policy towards benzodiazepine prescription could be detected ( P=0.275). Antidepressants were prescribed in 115 (55%) patients for an average duration of 476 (±360) days. There was no difference in benzodiazepine prescription (dosage, duration) between patients who had or had not been prescribed an antidepressant. Limitations: Patients were not been diagnosed systematically during the follow-up period. Conclusions: If measured longitudinally, the rate of benzodiazepine prescription after discontinuation is much higher than reported in previous studies that have measured this cross-sectionally. Successful discontinuation is a strong predictor of modest or no future benzodiazepine prescription. Two-thirds of patients altered their benzodiazepine usage after taking part in a discontinuation programme. Treatment with antidepressants does not seem to influence benzodiazepine prescription. Patients’ request (not GPs’policy) seems to be an important factor in continuing or resuming benzodiazepine prescription.