Economic burden of acute steroid-refractory graft-versus-host disease in commercially insured pediatric patients.

BACKGROUND: Acute graft-versus-host disease (aGVHD), a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT), often occurs within 100 days of HSCT. While steroids are typically used as first-line treatment, there is no consensus on second-line steroid-refractory (SR) treatments. SR aGVHD is associated with significantly worse pediatric health outcomes, but less is known about its economic impact. OBJECTIVE: To evaluate the economic burden of SR pediatric aGVHD in a commercially insured US patient population. METHODS: Retrospective analyses were conducted using medical and pharmacy claims data from the HealthCore Integrated Research Database (study period January 1, 2006-May 31, 2019). Included patients had at least 1 claim for allogeneic HSCT (earliest HSCT claim set as index date), no claims for autologous HSCT, and no pre-index GVHD. Patients were aged less than 18 years with no minimum pre- or post-index continuous enrollment. The GVHD cohort included patients with at least 1 claim for aGVHD over 100 days from index with at least 1 claim for any steroid and at least 1 claim for second-line therapy, both on or after the date of the first aGVHD claim. Patients post-HSCT with no GVHD claims over follow-up formed the comparison cohort. Health care resource utilization and costs over 12 months from the index date were calculated and compared between cohorts using parametric testing. RESULTS: 38 patients with SR aGVHD and 184 controls were included. Mean age and sex were similar for aGVHD (8.6 years, 50% female) and control (8.2 years, 45% female). During the 12-month post-index follow-up, SR aGVHD patients had higher rates of complications vs controls (* for P < 0.05): anemia (79% vs 68%), drug-induced anemia* (53% vs 34%), neutropenia (63% vs 53%), thrombocytopenia (58% vs 42%), gastrointestinal complications* (95% vs 65%), and infections* (95% vs 79%). Mean inpatient length of stay was longer by 31.6 days (P < 0.01) with a total average of 96.0 days for those with SR aGVHD vs 64.3 days for the controls. More SR aGVHD patients required inpatient total parenteral nutrition (71% vs 58%), readmission within 12 months of discharge from index hospitalization* (89% vs 60%), ER visits (34% vs 24%), and outpatient visits (100% vs 86%). Total 12-month mean medical costs were higher in aGVHD patients: $1,212,944 vs $673,491 (P < 0.001), mostly because of complication-related costs: $868,966 vs $396,757 (P < 0.001). Among patients with SR aGVHD, mean total costs were higher by about $1.8 million ($2,609,445 vs $812,385; P = 0.014) for those who died compared with those who were alive within 12 months. CONCLUSIONS: SR aGVHD in pediatric patients following HSCT is associated with incremental 12-month medical costs of greater than $500,000, driven largely by complications. DISCLOSURES: This research was sponsored by Mesoblast, Inc. Grabner is an employee of HealthCore, Inc., which acted as consultants to Mesoblast, Inc., during the conduct of this research. Strati is an employee of Mesoblast, Inc. Sandman and Forsythe are employees of Purple Squirrel Economics, which acted as consultants to Mesoblast, Inc., during the conduct of this research. This work was presented at the AMCP Annual Meeting online in April 2020 and was an encore presentation at AMCP Nexus 2020 Virtual in October 2020.

Budget Impact of a Steroid-Eluting Sinus Implant Versus Sinus Surgery for Adult Chronic Sinusitis Patients with Nasal Polyps.

BACKGROUND: A corticosteroid-eluting sinus implant was recently approved by the FDA as a drug to treat adult patients with nasal polyps who have undergone previous endoscopic sinus surgery (ESS) of the ethmoid sinuses. ESS is performed in an operating room under general anesthesia, whereby diseased tissue and bone are removed to provide improved drainage. ESS typically involves dissection of 1 or more of the 4 paired sinus cavities (maxillary, ethmoid, sphenoid, or frontal). The implant, containing 1,350 mcg of mometasone furoate, is inserted by a physician in an office setting and offers controlled localized release of corticosteroid to the polypoid sinus tissue. The implant has demonstrated significant improvements in clinical testing; however, little research has been conducted on its economic impact. OBJECTIVE: To evaluate and quantify the budget impact to a commercial payer of using this implant instead of ESS in patients with nasal polyps after a previous ESS. Since essentially all patients with recurrent nasal polyps after ESS are patients with chronic sinusitis (CS) diagnosis, this study also identified patients with CS with nasal polyposis (CSwNP) for consistency with the patient population studied in clinical trials evaluating the implant. METHODS: A budget impact analysis was conducted from a U.S. commercial payer perspective over a 1-year time horizon with patients who received the implant or revision ESS. Primary outcomes of interest were annual total and per-member per-month (PMPM) direct health care costs. Costs were estimated using a decision analysis model, assuming 50% implant utilization as an alternative to revision ESS in eligible patients, with other levels (25%, 75%) also considered. The model utilized the results of a recently published analysis of 86,052 patients in the Blue Health Intelligence database, results from published clinical trials evaluating the implant, a literature review, and published Medicare national payment amounts. RESULTS: A commercial health plan with 1 million members could anticipate 1,000 CSwNP patients as candidates for receiving the implant or revision ESS. Estimated direct treatment costs for refractory CSwNP using only revision ESS are $11.03 million ($0.92 PMPM). If the implant replaced surgery in 50% of cases and if 63% those patients received a second treatment with the implant during the year, the estimated total cost savings would be $2.56 million ($0.21 PMPM). Cost savings associated with using the implant changed to $0.11 PMPM and $0.32 PMPM with implant adoption of 25% and 75%, respectively. CONCLUSIONS: In a large commercially insured U.S. population, annual revision ESS costs are substantial. Using the implant instead of revision ESS could result in considerable cost savings for payers at various levels of adoption. DISCLOSURES: This study was sponsored by Intersect ENT, which was involved in study design and manuscript review. Ernst and Imhoff are employed by CTI Clinical Trial and Consulting Services, which contracted with Intersect ENT to conduct this study. Ernst and Imhoff also report other financial support from Intersect ENT during the conduct of the study. DeConde reports personal fees from Intersect ENT during the conduct of the study, as well as personal fees from Optinose, Stryker Endoscopy, and Olympus, outside the submitted work. Manes reports grants from Intersect ENT during the conduct of the study, as well as grants from Optinose and Sanofi outside the submitted work.

Analysis of Expected Costs of Carpal Tunnel Syndrome Treatment Strategies.

BACKGROUND: Over 500 000 carpal tunnel releases costing over $2 billion are performed each year in the United States. The study's purpose is to perform a cost-minimizing analysis to identify the least costly strategy for carpal tunnel syndrome treatment utilizing existing success rates based on previously reported literature. METHODS: We evaluate the expected cost of various treatment strategies based on the likelihood of further treatments: (1) a single steroid injection followed by surgical release; (2) up to 2 steroid injections before surgical release; (3) 3 steroid injections before surgery, and (4) immediate surgical release. To reflect costs, we use our institution's billing charges to private payers and reimbursements from Medicare. A range of expected steroid injection success rates are employed based on previously published literature. RESULTS: Immediate surgical release is the costliest treatment with an expected cost of $2149 to $9927 per patient. For immediate surgical release to cost less than a single injection attempt, the probability of surgery after injection would need to exceed 80% in the Medicare reimbursement model and 87% in the institutional billing model. A single steroid injection with subsequent surgery, if needed, amounts to a direct cost savings of $359 million annually compared with immediate surgical release. Three injections before surgery, with "high" expected success rates, represent the cost-minimizing scenario. CONCLUSIONS: Although many factors must be considered when deciding upon treatment for carpal tunnel syndrome, direct payer cost is an important component, and the initial management with steroid injections minimizes these direct payer costs.

Comparison Between Image-Guided and Landmark-Based Glenohumeral Joint Injections for the Treatment of Adhesive Capsulitis: A Cost-Effectiveness Study.

OBJECTIVE: The purpose of this study was to determine the cost-effectiveness of landmark-based and image-guided intraarticular steroid injections for the initial treatment of a population with adhesive capsulitis. MATERIALS AND METHODS: A decision analytic model from the health care system perspective over a 6-month time frame for 50-year-old patients with clinical findings consistent with adhesive capsulitis was used to evaluate the incremental cost-effectiveness of three techniques for administering intraarticular steroid to the glenohumeral joint: landmark based (also called blind), ultrasound guided, and fluoroscopy guided. Input data on cost, probability, and utility estimates were obtained through a comprehensive literature search and from expert opinion. The primary effectiveness outcome was quality-adjusted life years (QALY). Costs were estimated in 2017 U.S. dollars. RESULTS: Ultrasound-guided injections were the dominant strategy for the base case, because it was the least expensive ($1280) and most effective (0.4096 QALY) strategy of the three options overall. The model was sensitive to the probabilities of getting the steroid into the joint by means of blind, ultrasound-guided, and fluoroscopy-guided techniques and to the costs of the ultrasound-guided and blind techniques. Two-way sensitivity analyses showed that ultrasound-guided injections were favored over blind and fluoroscopy-guided injections over a range of reasonable probabilities and costs. Probabilistic sensitivity analysis showed that ultrasound-guided injections were cost-effective in 44% of simulations, compared with 34% for blind injections and 22% for fluoroscopy-guided injections and over a wide range of willingness-to-pay thresholds. CONCLUSION: Ultrasound-guided injections are the most cost-effective option for the initial steroid-based treatment of patients with adhesive capsulitis. Blind and fluoroscopy-guided injections can also be cost-effective when performed by a clinician likely to accurately administer the medication into the correct location.

Cost-effectiveness of Lumbar Epidural Steroid Injections.

STUDY DESIGN: Longitudinal cohort. OBJECTIVE: To determine the cost per quality-adjusted life-year for lumbar epidural steroid injections (LESI). SUMMARY OF BACKGROUND DATA: Despite being a widely performed procedure, there are few studies evaluating the cost-effectiveness of LESIs. METHODS: Patients who had received LESI between June 2012 and July 2013 with EuroQOL-5D (EQ-5D) scores available before and after LESIs but before any surgical intervention were identified. Costs were calculated on the basis of the Medicare Fee Schedule multiplied by the number of LESIs received between the 2 clinic visits. Quality-adjusted life-years (QALYs) were calculated using the EQ-5D. RESULTS: Of 421 patients who had pre-LESI EQ-5D data, 323 (77%) had post-LESI data available; 200 females, 123 males, mean age: 59.2 ±â€Š14.2 years. Cost per LESI was $608, with most patients receiving 3 LESIs for more than 1 year (range: 1-6 yr). Mean QALY gained was 0.005. One hundred forty-five patients (45%) had a QALY gain (mean = 0.117) at a cost of $62,175 per QALY gained; 127 patients (40%) had a loss in QALY (mean = -0.120) and 51 patients (15%) had no change in QALY. Fourteen of the 145 patients who improved, and 29 of the 178 patients who did not, have medical comorbidities that precluded surgery. Thirty-two (22%) of 131 patients without medical comorbidities who improved and 57 (32%) of 149 patients without medical comorbidities who did not improve subsequently had undergone surgery (P = 0.015). CONCLUSION: LESI may not be cost-effective in patients with lumbar degenerative disorders. For the 145 patients who improved, cost per QALY gained was acceptable at $62,175. However, for the 178 patients with no gain or a loss in QALY, the economics are not reportable with a cost per QALY gained being theoretically infinite. Further studies are needed to identify specific patient populations who will benefit from LESI because the economic viability of LESI requires improved patient selection. LEVEL OF EVIDENCE: 2.

[Influence of initial protocolized treatment with steroids in length of stay and costs of community acquired pneumonia]. / Influencia de la protocolización del tratamiento inicial con corticoides en la estancia y costo de las neumonías adquiridas en la comunidad. Estudio prospectivo 2015.

OBJECTIVE: The aim of the study was to analyze the impact of steroid treatment in patients with community acquired pneumonia (CAP), both in length of stay and economical cost of admission at a clinical university hospital. METHODS: Prospective study of admitted patients with the diagnosis of CAP, both in Internal Medicine and Infectious diseases department. The study was conducted from January to march 2015; patients receiving steroids from diagnosis to end of antibiotic treatment were classified as group I; otherwise, they were considered in group II. Administration of steroids was done according to the criteria of the responsible. Cost was stablished according to CAP Diagnostic Related Group (DRG). RESULTS: Prevalence of patients younger than 65 year-old was higher in group I (p<0.05). In bivariate analyses, mean admission time was lower in group I (5.37 vs 8.88 days) (p<0.0005) and also economical cost (2,361 euros vs 3,907 euros) (p<0.0005). In multivariate analysis, factors independently associated to higher cost (>3,520 euros) were COPD (OR=2.602; 95% CI 1.074-6.305) and group II (patients with no steroids) (OR=6.2; p=0,007). CONCLUSIONS: No administration of steroids in patients with CAP was associated, together with COPD, with higher economical cost (evaluated by DRG/length of stay).

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis.

BACKGROUND & AIMS: Topical corticosteroids or dietary elimination are recommended as first-line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6-food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. METHODS: We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort-member level. Simulation parameters were defined by systematic review and meta-analysis to determine the base-case estimates and bounds of uncertainty for sensitivity analysis. Meta-regression models included adjustment for differences in study and cohort characteristics. RESULTS: In the base-case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5-year time horizon ($9261.58 vs $5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base-case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive. CONCLUSIONS: In a cost utility analysis comparing topical corticosteroids and SFED for first-line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient-level costs or quality of life.

A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines.

BACKGROUND: Allergic rhinitis (AR) is a common condition that can be treated with a number of different therapies. Treatments such as intranasal antihistamines (INAs) and intranasal steroids (INSs) are widely used by AR patients. For some allergy sufferers, a combination of therapies, specifically an INA and an INS, is required to address their symptoms. A new treatment, the formulation of azelastine hydrochloride and fluticasone pro-pionate used as a single spray (MP-AzeFlu), has become available for AR patients who need both types of treatment. In this regard, the comparison with the alternative concomitant use of INAs and INSs is of interest. The current study examines the health care resource utilization and costs for each cohort. OBJECTIVE: To examine the resource utilization and costs associated with AR for patients treated with MP-AzeFlu or concurrent therapy with single-ingredient INA and INS sprays (free-combination therapy). METHODS: A retrospective administrative claims study for commercially insured patients from a large U.S. health plan was performed. Patients with an AR diagnosis and a prescription claim for MP-AzeFlu or free-combination therapy between September 1, 2012, and September 30, 2013, were identified. Patients were aged at least 12 years at index date (first prescription fill for intranasal therapy) and were required to have 12 months pre-index and 6 months post-index of continuous enrollment. Health care resource utilization and costs were assessed for the post-index period. The cohorts were adjusted on baseline demographic and clinical characteristics using inverse propensity treatment weights. Other covariates, prescriber specialty, product switching during the post-index period, and pre-index total costs were included in the regression models measuring outcomes. One clinical characteristic of interest was the presence of asthma as comorbidity. A subset analysis of AR patients with asthma was also performed. RESULTS: All-cause-related pharmacy fills as well as pharmacy, medical, and total costs were significantly reduced by using MP-AzeFlu (N = 810) instead of the free combination of drugs (N = 726). For AR-related health care resource utilization, the MP-AzeFlu cohort had significantly fewer pharmacy fills than the free-combination cohort (1.01 and 1.17, respectively; P < 0.001) with no significant difference in outpatient services and specialist visits (P = 0.139 and P = 0.117, respectively). Six-month AR-related pharmacy and total costs were significantly lower (P < 0.001 and P = 0.001) for the MP-AzeFlu cohort ($128 and $334, respectively) than the free-combination cohort ($268 and $458, respectively). There was no statistically significant difference in AR-related medical costs between the 2 cohorts (P = 0.454). For the subcohort of AR patients with asthma, the MP-AzeFlu cohort had lower 6-month asthma resource utilization and costs than the free-combination cohort. CONCLUSIONS: These findings suggest that, for AR patients needing INAs and INSs, the single-spray formulation MP-AzeFlu had better economic outcomes than for patients who rely on the free combination of these agents. MP-AzeFlu also appears to keep asthma-related utilization and costs down for those AR patients who also suffer from asthma. Potential explanations for these findings are explored. DISCLOSURES: This study was funded by Meda Pharmaceuticals. Authors were either employed by Meda Pharmaceuticals or received consulting fees from Meda Pharmaceuticals. Comprehensive Health Insights and Sedaghat received funding from Meda Pharmaceuticals as a consultant to participate in this study. Dufour and Caldwell-Tarr are employees of Comprehensive Health Insights. Harrow is currently employed by TESARO. This study was conceived by Harrow, Dufour, and Caldwell-Tarr. All authors contributed to the design of the study. Dufour took the lead in data collection, along with Caldwell-Tarr, and data interpretion was performed by Harrow, along with the other authors. Analyses were performed by Dufour. The manuscript was written and revised by all authors.

Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation.

BACKGROUND: Diabetic retinopathy is an important cause of visual loss. Laser photocoagulation preserves vision in diabetic retinopathy but is currently used at the stage of proliferative diabetic retinopathy (PDR). OBJECTIVES: The primary aim was to assess the clinical effectiveness and cost-effectiveness of pan-retinal photocoagulation (PRP) given at the non-proliferative stage of diabetic retinopathy (NPDR) compared with waiting until the high-risk PDR (HR-PDR) stage was reached. There have been recent advances in laser photocoagulation techniques, and in the use of laser treatments combined with anti-vascular endothelial growth factor (VEGF) drugs or injected steroids. Our secondary questions were: (1) If PRP were to be used in NPDR, which form of laser treatment should be used? and (2) Is adjuvant therapy with intravitreal drugs clinically effective and cost-effective in PRP? ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) for efficacy but other designs also used. DATA SOURCES: MEDLINE and EMBASE to February 2014, Web of Science. REVIEW METHODS: Systematic review and economic modelling. RESULTS: The Early Treatment Diabetic Retinopathy Study (ETDRS), published in 1991, was the only trial designed to determine the best time to initiate PRP. It randomised one eye of 3711 patients with mild-to-severe NPDR or early PDR to early photocoagulation, and the other to deferral of PRP until HR-PDR developed. The risk of severe visual loss after 5 years for eyes assigned to PRP for NPDR or early PDR compared with deferral of PRP was reduced by 23% (relative risk 0.77, 99% confidence interval 0.56 to 1.06). However, the ETDRS did not provide results separately for NPDR and early PDR. In economic modelling, the base case found that early PRP could be more effective and less costly than deferred PRP. Sensitivity analyses gave similar results, with early PRP continuing to dominate or having low incremental cost-effectiveness ratio. However, there are substantial uncertainties. For our secondary aims we found 12 trials of lasers in DR, with 982 patients in total, ranging from 40 to 150. Most were in PDR but five included some patients with severe NPDR. Three compared multi-spot pattern lasers against argon laser. RCTs comparing laser applied in a lighter manner (less-intensive burns) with conventional methods (more intense burns) reported little difference in efficacy but fewer adverse effects. One RCT suggested that selective laser treatment targeting only ischaemic areas was effective. Observational studies showed that the most important adverse effect of PRP was macular oedema (MO), which can cause visual impairment, usually temporary. Ten trials of laser and anti-VEGF or steroid drug combinations were consistent in reporting a reduction in risk of PRP-induced MO. LIMITATION: The current evidence is insufficient to recommend PRP for severe NPDR. CONCLUSIONS: There is, as yet, no convincing evidence that modern laser systems are more effective than the argon laser used in ETDRS, but they appear to have fewer adverse effects. We recommend a trial of PRP for severe NPDR and early PDR compared with deferring PRP till the HR-PDR stage. The trial would use modern laser technologies, and investigate the value adjuvant prophylactic anti-VEGF or steroid drugs. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005408. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Implications of lumbar epidural steroid injections after lumbar surgery.

OBJECTIVE: Assess the relationship between performing lumbar epidural steroid injections (ESIs) after lumbar surgery and workers' compensation claim duration and cost. METHODS: A multivariate logistic regression was used to determine the association between performing ESI after the first lumbar surgery in 11,394 lost time injury claims filed from 1999 to 2002 followed for 7 years postinjury. RESULTS: Odds ratio of costs more than $100,000 is 6.49 (95% confidence interval: 4.30 to 9.81) for ever having lumbar ESI after the first lumbar surgery, compared with no spinal procedures, controlling for sex, age, attorney involvement, opioid use, other spinal procedures, and claim duration. Odds ratio of having claim duration longer than 1000 days was 14.73 (95% confidence interval: 7.01 to 30.95). CONCLUSION: Lumbar ESI after the first lumbar surgery was associated with high cost and longer claim duration.

A systematic review to assess comparative effectiveness studies in epidural steroid injections for lumbar spinal stenosis and to estimate reimbursement amounts.

OBJECTIVE: To systematically appraise published comparative effectiveness evidence (clinical and economic) of epidural steroid injections (ESI) for lumbar spinal stenosis and to estimate Medicare reimbursement amounts for ESI procedures. TYPE: Systematic review. LITERATURE SURVEY: PubMed, Embase, and CINAHL were searched through August 2012 for key words that pertain to low back pain, spinal stenosis or sciatica, and epidural steroid injection. We used institutional and Medicare reimbursement amounts for our cost estimation. Articles published in English that assessed ESIs for adults with lumbar spinal stenosis versus a comparison intervention were included. Our search identified 146 unique articles, and 138 were excluded due to noncomparative study design, not having a study population with lumbar spinal stenosis, not having an appropriate outcome, or not being in English. We fully summarized 6 randomized controlled trials and 2 large observational studies. METHODOLOGY: Randomized controlled trial articles were reviewed, and the study population, sample size, treatment groups, ESI dosage, ESI approaches, concomitant interventions, outcomes, and follow-up time were reported. Descriptive resource use estimates for ESIs were calculated with use of data from our institution during 2010 and Medicare-based reimbursement amounts. SYNTHESIS: ESIs or anesthetic injections alone resulted in better short-term improvement in walking distance compared with control injections. However, there were no longer-term differences. No differences between ESIs versus anesthetic in self-reported improvement in pain were reported. Transforaminal approaches had better improvement in pain scores (≤4 months) compared with interlaminar injections. Two observational studies indicated increased rates of lumbar ESI in Medicare beneficiaries. Our sample included 279 patients who received at least 1 ESI during 2010, with an estimated mean total outpatient reimbursement for one ESI procedure "event" to be $637, based on 2010 Medicare reimbursement amounts ($505 technical and $132 professional payments). CONCLUSION: This systematic review of ESI for treating lumbar spinal stenosis found a limited amount of data that suggest that ESI is effective in some patients for improving select short-term outcomes, but results differed depending on study design, outcome measures used, and comparison groups evaluated. Overall, there are relatively few comparative clinical or economic studies for ESI procedures for lumbar spinal stenosis in adults, which indicated a need for additional evidence.

Management of frozen shoulder: a systematic review and cost-effectiveness analysis.

BACKGROUND: Frozen shoulder is condition in which movement of the shoulder becomes restricted. It can be described as either primary (idiopathic) whereby the aetiology is unknown, or secondary, when it can be attributed to another cause. It is commonly a self-limiting condition, of approximately 1 to 3 years' duration, though incomplete resolution can occur. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of treatments for primary frozen shoulder, identify the most appropriate intervention by stage of condition and highlight any gaps in the evidence. DATA SOURCES: A systematic review was conducted. Nineteen databases and other sources including the Cumulative Index to Nursing and Allied Health (CINAHL), Science Citation Index, BIOSIS Previews and Database of Abstracts of Reviews of Effects (DARE) were searched up to March 2010 and EMBASE and MEDLINE up to January 2011, without language restrictions. MEDLINE, CINAHL and PsycINFO were searched in June 2010 for studies of patients' views about treatment. REVIEW METHODS: Randomised controlled trials (RCTs) evaluating physical therapies, arthrographic distension, steroid injection, sodium hyaluronate injection, manipulation under anaesthesia, capsular release or watchful waiting, alone or in combination were eligible for inclusion. Patients with primary frozen shoulder (with or without diabetes) were included. Quasi-experimental studies were included in the absence of RCTs and case series for manipulation under anaesthesia (MUA) and capsular release only. Full economic evaluations meeting the intervention and population inclusion criteria of the clinical review were included. Two researchers independently screened studies for relevance based on the inclusion criteria. One reviewer extracted data and assessed study quality; this was checked by a second reviewer. The main outcomes of interest were pain, range of movement, function and disability, quality of life and adverse events. The analysis comprised a narrative synthesis and pair-wise meta-analysis. A mixed-treatment comparison (MTC) was also undertaken. An economic decision model was intended, but was found to be implausible because of a lack of available evidence. Resource use was estimated from clinical advisors and combined with quality-adjusted life-years obtained through mapping to present tentative cost-effectiveness results. RESULTS: Thirty-one clinical effectiveness studies and one economic evaluation were included. The clinical effectiveness studies evaluated steroid injection, sodium hyaluronate, supervised neglect, physical therapy (mainly physiotherapy), acupuncture, MUA, distension and capsular release. Many of the studies identified were at high risk of bias. Because of variation in the interventions and comparators few studies could be pooled in a meta-analysis. Based on single RCTs, and for some outcomes only, short-wave diathermy may be more effective than home exercise. High-grade mobilisation may be more effective than low-grade mobilisation in a population in which most patients have already had treatment. Data from two RCTs showed that there may be benefit from adding a single intra-articular steroid injection to home exercise in patients with frozen shoulder of < 6 months' duration. The same two trials showed that there may be benefit from adding physiotherapy (including mobilisation) to a single steroid injection. Based on a network of nine studies the MTC found that steroid combined with physiotherapy was the only treatment showing a statistically and clinically significant beneficial treatment effect compared with placebo for short-term pain (standardised mean difference -1.58, 95% credible interval -2.96 to -0.42). This analysis was based on only a subset of the evidence, which may explain why the findings are only partly supportive of the main analysis. No studies of patients' views about the treatments were identified. Average costs ranged from £36.16 for unguided steroid injections to £2204 for capsular release. The findings of the mapping suggest a positive relationship between outcome and European Quality of Life-5 Dimensions (EQ-5D) score: a decreasing visual analogue scale score (less pain) was accompanied by an increasing (better) EQ-5D score. The one published economic evaluation suggested that low-grade mobilisation may be more cost-effective than high-grade mobilisation. Our tentative cost-effectiveness analysis suggested that steroid alone may be more cost-effective than steroid plus physiotherapy or physiotherapy alone. These results are very uncertain. LIMITATIONS: The key limitation was the lack of data available. It was not possible to undertake the planned synthesis exploring the influence of stage of frozen shoulder or the presence of diabetes on treatment effect. As a result of study diversity and poor reporting of outcome data there were few instances where the planned quantitative synthesis was possible or appropriate. Most of the included studies had a small number of participants and may have been underpowered. The lack of available data made the development of a decision-analytic model implausible. We found little evidence on treatment related to stage of condition, treatment pathways, the impact on quality of life, associated resource use and no information on utilities. Without making a number of questionable assumptions modelling was not possible. CONCLUSIONS: There was limited clinical evidence on the effectiveness of treatments for primary frozen shoulder. The economic evidence was so limited that no conclusions can be made about the cost-effectiveness of the different treatments. High-quality primary research is required.

Study protocol- Lumbar Epidural steroid injections for Spinal Stenosis (LESS): a double-blind randomized controlled trial of epidural steroid injections for lumbar spinal stenosis among older adults.

BACKGROUND: Lumbar spinal stenosis is one of the most common causes of low back pain among older adults and can cause significant disability. Despite its prevalence, treatment of spinal stenosis symptoms remains controversial. Epidural steroid injections are used with increasing frequency as a less invasive, potentially safer, and more cost-effective treatment than surgery. However, there is a lack of data to judge the effectiveness and safety of epidural steroid injections for spinal stenosis. We describe our prospective, double-blind, randomized controlled trial that tests the hypothesis that epidural injections with steroids plus local anesthetic are more effective than epidural injections of local anesthetic alone in improving pain and function among older adults with lumbar spinal stenosis. METHODS: We will recruit up to 400 patients with lumbar central canal spinal stenosis from at least 9 clinical sites over 2 years. Patients with spinal instability who require surgical fusion, a history of prior lumbar surgery, or prior epidural steroid injection within the past 6 months are excluded. Participants are randomly assigned to receive either ESI with local anesthetic or the control intervention (epidural injections with local anesthetic alone). Subjects receive up to 2 injections prior to the primary endpoint at 6 weeks, at which time they may choose to crossover to the other intervention.Participants complete validated, standardized measures of pain, functional disability, and health-related quality of life at baseline and at 3 weeks, 6 weeks, and 3, 6, and 12 months after randomization. The primary outcomes are Roland-Morris Disability Questionnaire and a numerical rating scale measure of pain intensity at 6 weeks. In order to better understand their safety, we also measure cortisol, HbA1c, fasting blood glucose, weight, and blood pressure at baseline, and at 3 and 6 weeks post-injection. We also obtain data on resource utilization and costs to assess cost-effectiveness of epidural steroid injection. DISCUSSION: This study is the first multi-center, double-blind RCT to evaluate the effectiveness of epidural steroid injections in improving pain and function among older adults with lumbar spinal stenosis. The study will also yield data on the safety and cost-effectiveness of this procedure for older adults. TRIAL REGISTRATION: Clinicaltrials.gov NCT01238536.

Outcomes and cost comparison of three therapeutic approaches to allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a global health problem because of its increasing impact on economics, society, and the individual's quality of life. This study compares the outcomes and cost of three intranasal therapeutic approaches to the treatment of AR. METHODS: This was a retrospective cohort study using propensity scores to achieve balanced cohorts. The study population included patients ≥16 years of age with at least one intranasal prescription claim, without concurrent nasal polyps or sinusitis. Health care use and costs, airway infections, pharmacy costs, and indicators of unsatisfactory treatment (i.e., treatment augmentation or switching) were evaluated in the 1-year follow-up period using a claims database. RESULTS: Data from 141,190 patients in intranasal antihistamines (INA) therapy, intranasal steroids (INS) therapy, and intranasal combination therapy (ICT) cohorts were analyzed. The INA cohort showed the lowest rate of change in treatment (switching or augmentation). Switching rates were lowest in the INS therapy cohort, whereas augmentation was lowest in the INA cohort. AR- and asthma-related medication costs were significantly lower in the INA cohort. No differences were observed in airway infections and overall health care costs. Concurrent chronic obstructive pulmonary disorder and asthma were the strongest predictors of health care cost and respiratory infection in the follow-up period. CONCLUSION: A change in treatment was noted in ∼⅓ of the entire study population. None of the treatments had a remarkable effect on health care costs or the occurrence of airway infections. The INA treatment cohort had lower AR- and asthma-related medication costs.

Thiopurine S- methyltransferase [corrected] testing in idiopathic pulmonary fibrosis: a pharmacogenetic cost-effectiveness analysis.

Azathioprine in combination with N-acetylcysteine (NAC) and steroids is a standard therapy for idiopathic pulmonary fibrosis (IPF). Its use, however, is limited by its side effects, principally leukopenia. A genotypic assay, thiopurine S-methyltransferase (TPMT), has been developed that can potentially identify those at risk for developing leukopenia with azathioprine, and thereby limit its toxicity. In those with abnormal TPMT activity, azathioprine can be started at lower dose or an alternate regimen selected. Determine the cost-effectiveness of a treatment strategy using TPMT testing before initiation of azathioprine, NAC, and steroids in IPF by performing a computer-based simulation. We developed a decision analytic model comparing three strategies: azathioprine, NAC and steroids with and without prior TPMT testing, and conservative therapy, consisting of only supportive measures. Prevalence of abnormal TPMT alleles and complication rates of therapy were taken from the literature. We assumed a 12.5% incidence of abnormal TPMT alleles, 4% overall incidence of leukopenia while taking azathioprine, and that azathioprine, NAC, and steroids in combination reduced IPF disease progression by 14% during 12 months. TPMT testing before azathioprine, NAC, and steroids was the most effective and most costly strategy. The marginal cost-effectiveness of the TPMT testing strategy was $49,156 per quality adjusted life year (QALY) gained versus conservative treatment. Compared with azathioprine, NAC and steroids without prior testing, the TPMT testing strategy cost only $29,662 per QALY gained. In sensitivity analyses, when the prevalence of abnormal TPMT alleles was higher than our base case, TPMT was "cost-effective." At prevalence rates lower than our base case, it was not. TPMT testing before initiating therapy with azathioprine, NAC, and steroids is a cost-effective treatment strategy for IPF.