Impact of Biologics and Small-Molecule Agents on Postoperative Complications in IBD: A Systematic Review.

BACKGROUND: Patients with IBD may require colectomy for severe disease unresponsive or refractory to pharmacological therapy. The question of the impact of biologic use on postoperative complications is a topic of active investigation. OBJECTIVE: A systematic literature review was performed to describe the current state of knowledge of the impact of perioperative biologic and tofacitinib use on postoperative complications in patients with IBD. DATA SOURCES: PubMed and Cochrane databases were searched. STUDY SELECTION: Studies between January 2000 and January 2023, in any language, were searched, followed by a snowball search identifying further studies in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Articles regarding pediatric or endoscopic management were excluded. INTERVENTIONS: Preoperative or perioperative exposure to biologics in IBD was included. MAIN OUTCOME MEASURES: Infectious and noninfectious complications, including anastomotic leaks, surgical site infections, urinary tract infections, pneumonia, sepsis, septic shock, postoperative length of stay, readmission, and reoperation, were the main outcomes measured. RESULTS: A total of 28 studies were included for analysis in this review, including 7 meta-analyses or systematic reviews and 5 randomized studies. Snowball search identified 11 additional studies providing topical information. Overall, tumor necrosis factor inhibitors likely do not increase the risk of postoperative adverse outcomes, while data on other biologics and small-molecule agents are emerging. LIMITATIONS: This is a qualitative review including all study types. The varied nature of study types precludes quantitative comparison. CONCLUSIONS: Although steroids increase postoperative infectious and noninfectious complications, tumor necrosis factor inhibitors do not appear to increase postoperative infectious and noninfectious complications. There is a need for further perioperative data for other agents. See video from symposium .

Examining Diversity: a Content Analysis of Cancer Depictions on Primetime Scripted Television.

Entertainment programming provides a unique opportunity for cancer education, particularly for higher risk racial and ethnic minority groups. Cultural relevancy is key to quality narrative cancer communication, and minorities often prefer media content produced by and featuring members of their own cultural in-group. However, little is known about whether cancer depictions or the television programs they appear in are culturally diverse. Using media content analysis, this study aims to assess the cultural diversity of cancer depictions on primetime scripted television to reveal opportunities to improve cancer education through entertainment. Indicators used to assess cultural diversity at the program level and depiction levels were collected. Out of 111 television programs, 10 (9.01%) programs mentioned cancer, from which 37 cancer depictions were identified. However, the majority of cancer depictions involved White patients and White health providers. Depictions of coping and treatment also dominated with less than 10% of depictions discussing cancer prevention. These patterns reveal a missed opportunity in existing cancer narratives on primetime scripted television and a lack of representation of cultural, social, and environmental factors that affect the health of minority communities, who need to hear these messages the most.

Every 2-month belatacept maintenance therapy in kidney transplant recipients greater than 1-year posttransplant: A randomized, noninferiority trial.

Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous infusions. Every 2-month (q2m) belatacept has potential to increase utilization, therefore we conducted a randomized noninferiority trial in low immunologic risk renal transplant recipients greater than 1-year posttransplant. Patients on belatacept were randomly assigned to q1m or q2m therapy. The primary objective was a noninferiority comparison of renal function (eGFR) at 12 months with a noninferiority margin (NIM) of 6.0 ml/min/1.73 m2 . One hundred and sixty-six participants were randomized to q1m (n = 82) or q2m (n = 84) belatacept, 163 patients received treatment, and 76 q1m and 77 q2m subjects completed the 12-month study period. Every 2-month belatacept was noninferior to q1m, as the difference in mean eGFR adjusted for baseline renal function did not exceed the NIM. Two-month dosing was safe and well tolerated, with no patient deaths or graft losses. Four rejection episodes and three cases of donor-specific antibodies (DSAs) occurred among q2m subjects; however, only one rejection and one instance of DSA were observed in subjects adherent to the study protocol. Every 2-month belatacept therapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies with long-term follow-up will further elucidate immunologic risk. (ClinicalTrials.gov NCT02560558).

AAPM WGPE report 394: Simulated error training for the physics plan and chart review.

BACKGROUND: Simulated error training is a method to practice error detection in situations where the occurrence of error is low. Such is the case for the physics plan and chart review where a physicist may check several plans before encountering a significant problem. By simulating potentially hazardous errors, physicists can become familiar with how they manifest and learn from mistakes made during a simulated plan review. PURPOSE: The purpose of this project was to develop a series of training datasets that allows medical physicists and trainees to practice plan and chart reviews in a way that is familiar and accessible, and to provide exposure to the various failure modes (FMs) encountered in clinical scenarios. METHODS: A series of training datasets have been developed that include a variety of embedded errors based on the risk-assessment performed by American Association of Physicists in Medicine (AAPM) Task Group 275 for the physics plan and chart review. The training datasets comprise documentation, screen shots, and digital content derived from common treatment planning and radiation oncology information systems and are available via the Cloud-based platform ProKnow. RESULTS: Overall, 20 datasets have been created incorporating various software systems (Mosaiq, ARIA, Eclipse, RayStation, Pinnacle) and delivery techniques. A total of 110 errors representing 50 different FMs were embedded with the 20 datasets. The project was piloted at the 2021 AAPM Annual Meeting in a workshop where participants had the opportunity to review cases and answer survey questions related to errors they detected and their perception of the project's efficacy. In general, attendees detected higher-priority FMs at a higher rate, though no correlation was found between detection rate and the detectability of the FMs. Familiarity with a given system appeared to play a role in detecting errors, specifically when related to missing information at different locations within a given software system. Overall, 96% of respondents either agreed or strongly agreed that the ProKnow portal and training datasets were effective as a training tool, and 75% of respondents agreed or strongly agreed that they planned to use the tool at their local institution. CONCLUSIONS: The datasets and digital platform provide a standardized and accessible tool for training, performance assessment, and continuing education regarding the physics plan and chart review. Work is ongoing to expand the project to include more modalities, radiation oncology treatment planning and information systems, and FMs based on emerging techniques such as auto-contouring and auto-planning.

Feasibility of a Self-directed Upper Extremity Training Program to Promote Actual Arm Use for Individuals Living in the Community With Chronic Stroke.

Objective: To determine the feasibility of a self-directed training protocol to promote actual arm use in everyday life. The secondary aim was to explore the initial efficacy on upper extremity (UE) outcome measures. Design: Feasibility study using multiple methods. Setting: Home and outpatient research lab. Participants: Fifteen adults (6 women, 9 men, mean age=53.08 years) with chronic stroke living in the community. There was wide range of UE functional levels, ranging from dependent stabilizer (limited function) to functional assist (high function). Intervention: Use My Arm-Remote protocol. Phase 1 consisted of clinician training on motivational interviewing (MI). Phase 2 consisted of MI sessions with participants to determine participant generated goals, training activities, and training schedules. Phase 3 consisted of UE task-oriented training (60 minutes/day, 5 days/week, for 4 weeks). Participants received daily surveys through an app to monitor arm training behavior and weekly virtual check-ins with clinicians to problem-solve challenges and adjust treatment plans. Outcome Measures: Primary outcome measures were feasibility domains after intervention, measured by quantitative study data and qualitative semi-structured interviews. Secondary outcomes included the Canadian Occupational Performance Measure (COPM), Motor Activity Log (MAL), Fugl-Meyer Assessment (FMA), and accelerometry-based duration of use metric measured at baseline, discharge, and 4-week follow-up. Results: The UMA-R was feasible in the following domains: recruitment rate, retention rate, intervention acceptance, intervention delivery, adherence frequency, and safety. Adherence to duration of daily practice did not meet our criteria. Improvements in UE outcomes were achieved at discharge and maintained at follow-up as measured by COPM-Performance subscale (F[1.42, 19.83]=17.72, P<.001) and COPM-Satisfaction subscale (F[2, 28]=14.73, P<.001), MAL (F[1.31, 18.30]=12.05, P<.01) and the FMA (F[2, 28]=16.62, P<.001). Conclusion: The UMA-R was feasible and safe to implement for individuals living in the community with chronic stroke. Adherence duration was identified as area of refinement. Participants demonstrated improvements in standardized UE outcomes to support initial efficacy of the UMA-R. Shared decision-making and behavior change frameworks can support the implementation of UE self-directed rehabilitation. Our results warrant the refinement and further testing of the UMA-R.

Protocol for a remote home-based upper extremity self-training program for community-dwelling individuals after stroke.

Background: Half of all stroke survivors experience hemiparesis on the contralateral side, resulting in chronic upper extremity (UE) impairment. Remote rehabilitation is a promising approach to optimize the gains made in the clinic to maximize function and promote UE use at home. This paper describes the study protocol for a remote home-based UE self-training program. Design: This was a feasibility study that used a convergent mixed methods approach. Methods: We collected data on 15 community-dwelling individuals with UE hemiparesis after stroke. The study used motivational interviewing (MI) and ecological momentary assessments (EMA) to maximize engagement in a 4-week personalized UE self-training program. The study consisted of three phases: 1) training in MI for the interventionists 2) creating customized treatment plans using shared decision making, and 3) four weeks of UE self-training. Measures and analysis: To evaluate feasibility, we will summarize recruitment and retention rates, intervention delivery, acceptance, adherence, and safety. Quantitative UE outcomes will measure change in UE status after the intervention (Fugl-Meyer Assessment, Motor Activity Log, Canadian Occupational Performance Measure, and bilateral magnitude ratio). Qualitative data (1:1 semi-structured interviews) will capture participants' perceptions and experience with the intervention. Quantitative and qualitative data will be integrated to gain a deeper understanding of the facilitators and barriers for engagement and adherence to UE self-training. Conclusion: The results of this study will advance the scientific knowledge for use of MI and EMA as methods for enhancing adherence and engagement in UE self-training in stroke rehabilitation. The ultimate impact of this research will be to improve UE recovery for individuals with stroke transitioning back into community. Clinical trials registration: NCT05032638.

Trainee autonomy and surgical outcomes after emergency gastrointestinal surgery.

BACKGROUND: Operative meaningful trainee autonomy is an essential component of surgical training. Reduced trainee autonomy is frequently attributed to patient safety concerns, but this has not been examined within Kenya. We aimed to assess whether meaningful trainee autonomy was associated with a change in patient outcomes. METHODS: We investigated whether meaningful trainee autonomy was associated with a change in severe postoperative complications and all-cause in-hospital mortality in a previously described cohort undergoing emergency gastrointestinal operations. Each operation was reviewed to determine the presence of meaningful autonomy, defined as "supervision only" from faculty. Comparisons were made between faculty-led cases and cases with meaningful trainee autonomy. Multilevel logistic regression models were created for the outcomes of mortality and complications with the exposure of meaningful trainee autonomy, accounting for fixed effects of the Africa Surgical Outcomes Study Risk Score and random effects of discharge diagnoses. RESULTS: After excluding laparoscopy (N = 28) and missing data (N = 3), 451 operations were studied, and 343 (76.1%) had meaningful trainee autonomy. Faculty were more involved in operations with older age, cancer, prior complications, and higher risk scores. On unadjusted analysis, meaningful trainee autonomy was associated with mortality odds of 0.32 (95% confidence interval: 0.17-0.58) compared with faculty-led operations. Similarly, the odds of developing complications were 0.52 (95% confidence interval: 0.32-0.84) with meaningful trainee autonomy compared with faculty-led operations. When adjusting for Africa Surgical Outcomes Study Score and clustering discharge diagnoses, the odds of mortality (odds ratio 0.58; 95% confidence interval: 0.27-1.2) and complication (odds ratio 0.83; 95% confidence interval: 0.47-1.5) were not significant. CONCLUSION: Our findings support that increasing trainee autonomy does not change patient outcomes in selected emergency gastrointestinal operations. Further, trainees and faculty appropriately discern patients at higher risk of complications and mortality, and the selective granting of trainee autonomy does not affect patient safety.

The effect of exercise post vertebral augmentation in osteoporotic patients: A systematic review and meta-analysis.

This meta-analysis investigated the effects of exercise on Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores following vertebroplasty or kyphoplasty in osteoporotic fractures. A literature search of PubMed, EMBASE (Elsevier), CiNAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 6, 2022. Eligible studies reported osteoporosis patients over 18 years of age with a diagnosis of at least one vertebral fracture via radiography or clinical assessment. This review was registered in PROSPERO (ID: CRD42022340791). Ten studies met the eligibility criteria (n = 889). VAS scores at baseline were 7.75 (95% CI: 7.54, 7.97, I2 = 76.11%). Following initiation of exercise, VAS scores at the endpoint of 12 months were 1.91 (95% CI: 1.53, 2.29, I2 = 92.69%). ODI scores at baseline were 68.66 (95% CI: 56.19, 81.13, I2 = 85%). Following initiation of exercise, ODI scores at the endpoint of 12 months were 21.20 (95% CI: 14.52, 27.87, I2 = 99.30). A two-arm analysis demonstrated improved VAS and ODI for the exercise group compared to non-exercise control at 6 months (MD = -0.70, 95% CI: -1.08, -0.32, I2 = 87% and MD = -6.48, 95% CI: -7.52, -5.44, I2 = 46%, respectively) and 12 months (MD = -0.88, 95% CI: -1.27, -0.49, I2 = 85% and MD = -9.62, 95% CI: -13.24, -5.99, I2 = 93%). Refracture was the only adverse event reported and occurred almost twice as frequently in the non-exercise group than in the exercise group. Exercise rehabilitation post vertebral augmentation is associated with improved pain and functionality, particularly after 6 months of exposure, and may reduce refracture rate.

Joy of gardening: a hospital-based cooking and gardening program.

BACKGROUND: Nutrition interventions aid in implementing healthy eating. Garden-enhanced nutrition intervention programs have been conducted in schools. We sought to assess feasibility of a hospital-based cooking and gardening program. METHODS: The cohort study implemented a 3-week integrated cooking and gardening program in the United States (Seattle, WA). We recruited participants with ages 8-15 years from ambulatory clinics. We conducted three 3-week series hospital-based cooking and gardening program. Children and parents were given pre- and post-program (1 year) surveys. The surveys assessed child participation in food preparation and gardening, strengths and weaknesses of the program, and identified parents' opinions towards sustaining healthy behaviors. RESULTS: Eighteen children participated in the hospital-based cooking and gardening program. At 1-year follow-up, 78% of participants were gardening at home and 100% of participants were cooking at home. CONCLUSIONS: Novel approaches to combat obesity are needed. A hospital-based cooking and gardening program is a novel intervention to consider for nutrition education.

Using Transitional Changes on High-Resolution Computed Tomography to Monitor the Impact of Cyclophosphamide or Mycophenolate Mofetil on Systemic Sclerosis-Related Interstitial Lung Disease.

OBJECTIVE: To examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis-related ILD (SSc-ILD). METHODS: We evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric high-resolution computed tomography (HRCT) scans obtained at baseline and after 2 years of therapy in patients treated with either cyclophosphamide (CYC) for 1 year or mycophenolate mofetil (MMF) for 2 years in Scleroderma Lung Study II. ILD patterns included lung fibrosis, ground glass, honeycombing, and normal lung. Net change was calculated as the difference in the probability of change from one ILD pattern to another. Wilcoxon's signed rank test was used to compare the changes. RESULTS: Forty-seven and 50 patients had baseline and follow-up scans in the CYC and MMF groups, respectively. Mean net improvements reflecting favorable changes from one ILD pattern to another in the whole lung in the CYC and MMF groups, respectively, were as follows: from lung fibrosis to a normal lung pattern, 21% and 19%; from a ground-glass pattern to a normal lung pattern, 30% and 28%; and from lung fibrosis to a ground-glass pattern, 5% and 0.5%. The mean overall improvement in transitioning from a ground-glass pattern or lung fibrosis to a normal lung pattern was significant for both treatments (all P < 0.001). CONCLUSION: Significantly favorable transitions from both ground-glass and lung fibrosis ILD patterns to a normal lung pattern were observed in patients undergoing immunosuppressive treatment for SSc-ILD, suggesting the usefulness of examining these transitions for insights into the underlying pathobiology of treatment response.

Efficacy of lamina terminalis fenestration in reducing shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage: a systematic review. Clinical article.

OBJECT: Chronic hydrocephalus requiring shunt placement is a common complication following aneurysmal subarachnoid hemorrhage (SAH). Controversy exists over whether microsurgical fenestration of the lamina terminalis during aneurysm surgery affords a reduction in the development of shunt-dependent hydrocephalus. To resolve this debate, the authors performed a systematic review and quantitative analysis of the literature to determine the efficacy of lamina terminalis fenestration in reducing aneurysmal SAH-associated shunt-dependent hydrocephalus. METHODS: A MEDLINE (1950-2007) database search was performed using the following keywords, singly and in combination: "ventriculoperitoneal shunt," "hydrocephalus," "subarachnoid hemorrhage," "aneurysm," "fenestration," and "lamina terminalis." Additional studies were manually singled out by scrutinizing references from identified manuscripts, major neurosurgical journals and texts, and personal files. A recent study from the authors' institution was also incorporated into the review. Data from included studies were analyzed using the chi-square analysis and Student t-test. The Cochran-Mantel-Haenszel test was used to compare overall incidence of shunt-dependent hydrocephalus. RESULTS: The literature search revealed 19 studies, but only 11 were included in this review, involving 1973 patients. The fenestrated and nonfenestrated cohorts (combined from the various studies) differed significantly with regard to patient sex, age, and clinical grade as well as aneurysm location (p=0.0065, 0.0028, 0.0003, and 0.017, respectively). The overall incidence of shunt-dependent hydrocephalus in the fenestrated cohort was 10%, as compared with 14% in the nonfenestrated cohort (p=0.089). The relative risk of shunt-dependent hydrocephalus in the fenestrated cohort was 0.88 (95% CI 0.62-1.24). CONCLUSIONS: This systematic review revealed no significant association between lamina terminalis fenestration and a reduced incidence of shunt-dependent hydrocephalus. The interpretation of these results, however, is restricted by unmatched cohort differences as well as other inherent study limitations. Although the overall literature supports lamina terminalis fenestration, a number of authors have questioned the technique's benefits, thus rendering its efficacy in reducing shunt-dependent hydrocephalus unclear. A well-designed, multicenter, randomized controlled trial is needed to definitively address the efficacy of this microsurgical technique.

Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database.

BACKGROUND/OBJECTIVES: Addition of cilostazol or sarpogrelate to the standard dual antiplatelet therapy of aspirin and clopidogrel has been implemented in patients that underwent percutaneous coronary intervention (PCI) with stents in Korea. This study aimed to evaluate the efficacy and safety of triple antiplatelet therapies. METHODS: This retrospective cohort study was performed using the Korean National Insurance Claim Data of the Health Insurance Review and Assessment Service from January 1, 2009 to December 31, 2014. The study cohort population consisted of patients with ischemic heart diseases and a history of PCI. They were treated with antiplatelet therapy of aspirin, clopidogrel (AC); aspirin, clopidogrel, cilostazol (ACCi); or aspirin, clopidogrel, sarpogrelate (ACSa) during the index period from January 1, 2010 to December 31, 2011. During the follow-up period up to December 31, 2014, the major adverse cardiac or cerebral events (MACCE) including death, myocardial infarction, target lesion revascularization, and ischemic stroke were assessed. Bleeding complications were also evaluated as adverse drug events. RESULTS: Out of 93,876 patients with PCI during the index period, 69,491 patients started dual (AC) or triple therapy (ACSa or ACCi). The clinical outcomes of comparing ACSa and ACCi therapy showed beneficial effects in the ACSa group in the prevention of subsequent cardiac or cerebral events. After Propensity score-matching between ACSa and ACCi groups, there were significant differences in MI and revascularization, with corresponding HR of 0.38 (95% CI, 0.20-0.73) and 0.66 (95% CI, 0.53-0.82) in ACSa vs. ACCi at 12 months, respectively. At the 24-month follow-up, the triple therapy groups (ACS or ACC) had a higher incidence of MACCE compared to the dual therapy (AC) group; ACSa vs. AC HR of 1.69 (95% CI, 1.62-1.77); ACC vs. AC HR of 1.22 (95% CI, 1.06-1.41). There was no significant difference in severe or life-threatening bleeding risk among three groups; ACSa vs. AC, HR of 0.68 (95% CI, 0.37-1.24), ACCi vs. AC, HR of 0.91 (95% CI, 0.77-1.09). CONCLUSION: Sarpogrelate-containing triple antiplatelet therapy demonstrated comparable rates of MACCE prevention to the conventional dual antiplatelet therapy after PCI without significantly increasing bleeding risk during the two-year follow-up period.

Therapeutic duplicate prescribing in Korean ambulatory care settings using the National Health Insurance claim data.

BACKGROUND: Duplicate prescribing is known to occur across health systems and is one of the most frequent drug related problems. Therapeutic duplication (TD) increases the risk of adverse drug reactions without additional therapeutic benefits. OBJECTIVES: This study aimed to develop TD criteria concerning four drug categories which are acid-related disorder drugs, antimicrobials, antihypertensives, and lipid modifying drugs and to estimate the prevalence of therapeutic duplicate prescribing at the ambulatory care settings in Korea. METHODS: TD criteria were developed using the WHO anatomical therapeutic chemical classification and modified with an expert consensus panel using the Delphi method. The prevalence of TD including ingredient duplication (ID) of four drug categories was examined using National Health Insurance claim database including 15 million patients during one month in 2009 (December). TD was defined as prescribing medications within the same category in the developed TD criteria list. RESULTS: The numbers of patients who received acid-related disorder drugs, antimicrobials, antihypertensives, and lipid-modifying drugs in the study period were 10,049,292, 7,584,131, 4,349,945, and 1,425,292 respectively. In the field of acid-related disorder drugs prescribed, there were 0.3 % IDs and 2.5 % TDs within a prescription issued by one prescriber. There were 8.4 % IDs and 14.5 % TDs between prescriptions issued at different ambulatory visits. In the field of antimicrobial medicines, there were 0.1 % IDs and 2.6 % TDs within a prescription, while there were 5.0 % IDs and 7.6 % TDs between different prescriptions. Amongst the antihypertensives prescribed, there were 0.4 % IDs and 1.9 % TDs within a prescription, while there were 9.9 % IDs and 11.5 % TDs between prescriptions. Lastly, looking at lipid-modifying drugs prescribed, there were 0.3 % IDs and 0.5 % TDs within one prescription, while there were 8.9 % IDs and 9.4 % TDs between prescriptions. CONCLUSION: The prevalence of duplicate prescribing was substantial in the ambulatory care setting which is to be improved using the TD criteria developed from this study in the national drug utilization review system in Korea.

Pedicled extranasal flaps in skull base reconstruction.

Cerebrospinal fluid (CSF) leaks most commonly arise during or after skull base surgery, although they occasionally present spontaneously. Recent advances in the repair of CSF leaks have enabled endoscopic endonasal surgery to become the preferred option for management of skull base pathology. Small defects (<1 cm) can be repaired by multilayered free grafts. For large defects (>3 cm), pedicled vascular flaps are the repair method of choice, resulting in much lower rates of postoperative CSF leaks. The pedicled nasoseptal flap (NSF) constitutes the primary reconstructive option for the vast majority of skull base defects. It has a large area of potential coverage and high rates of success. However, preoperative planning is required to avoid sacrificing the NSF during resection. In cases where the NSF is unavailable, often due to tumor involvement of the septum or previous resection removing or compromising the flap, other flaps may be considered. These flaps include intranasal options - inferior turbinate or middle turbinate flaps - as well as regional pedicled flaps: pericranial flap, temporoparietal fascial flap, or palatal flap. More recently, novel alternatives such as the pedicled facial buccinator flap and the pedicled occipital galeopericranial flap have been added to the arsenal of options for skull base reconstruction. Characteristics of and appropriate uses for each flap are described.

Continuous intravesical lidocaine treatment for interstitial cystitis/bladder pain syndrome: safety and efficacy of a new drug delivery device.

Limited treatment options exist for patients who suffer from a painful bladder condition known as interstitial cystitis/bladder pain syndrome (IC/BPS). Whether given systemically (orally) or by short-duration (1 to 2 hours) exposure via intravesical instillation, therapeutic agents have exhibited poor efficacy because their concentrations in the bladder are low. A previous attempt to develop a drug delivery device for use in the bladder was unsuccessful, likely as a result of poor tolerability. A continuous lidocaine-releasing intravesical system (LiRIS) was designed to be retained in the bladder and release therapeutic amounts of the drug into urine over a period of 2 weeks. The device was tested in healthy volunteers and IC/BPS patients and was found to be well tolerated in both subject groups because of its small size and freedom of movement within the bladder. The 16 women with IC/BPS who were enrolled in the study met the National Institute of Diabetes and Digestive and Kidney Diseases criteria for bladder hemorrhages or Hunner's lesions. Subjects received either LiRIS 200 mg or LiRIS 650 mg for 2 weeks. Safety, efficacy, cystoscopic appearance of the bladder, and limited pharmacokinetic data were collected. Both doses were well tolerated, and clinically meaningful reductions were seen in pain, urgency, voiding frequency, and disease questionnaires. Cystoscopic examinations showed improvement on day 14 (day of removal) compared with day 1, including resolution of Hunner's lesions in five of six subjects with baseline lesions. Global response assessment showed an overall responder rate of 64% at day 14 and a sustained overall responder rate of 64% 2 weeks later. Extended follow-up suggests that the reduction in pain was maintained for several months after the device was removed.

Is discharge knee range of motion a useful and relevant clinical indicator after total knee replacement? Part 1.

OBJECTIVES: Knee range of motion (ROM) at the point of discharge from acute care is used as a clinical indicator to benchmark performance between hospital services after total knee replacement (TKR). The utility of the current benchmark, including whether discharge ROM varies between hospitals, is unknown. This study aimed to determine whether the benchmark [≥80 degrees flexion and ≤5 degrees fixed flexion (extension)] is realistic and whether the service provider is a predictor of knee ROM. METHODS: A prospective, observational cohort study was conducted involving 176 TKR patients from four hospitals. Knee ROM was photographically assessed preoperatively and at discharge. 'Hospital', typical patient demographic data and preoperative ROM were identified a priori as potential predictors of knee ROM. RESULTS: Overall, 2% [95% CI (confidence interval) 1-6] of patients attained the ROM benchmark. Individual hospital attainment of the benchmark ranged 0-7% with a significant difference (P = 0.047) evident between the best performer and the remaining hospitals. The overall rates of attainment of the individual flexion (25%, 95% CI 19-32) and extension (15%, 95% CI 10-21) components were similarly low, although the scatter between hospitals was large [flexion (2-47%); extension (8-44%)]. Preoperative flexion and hospital were significant (P = 0.002) predictors of discharge flexion, explaining 21% of the variance. Similarly, hospital and preoperative extension together with gender were significant (P < 0.001) predictors of discharge extension, explaining 26% of the variance. CONCLUSIONS: A small minority of patients attained the knee ROM benchmark, indicating the existing standard is unrealistic. Nevertheless, that 'hospital' is an important predictor confirms the potential of ROM for benchmarking purposes. Differences in physiotherapy practices may contribute to inter-hospital variation in discharge knee ROM together with other undefined factors. The causal relationships explaining the variation and the relationship between discharge ROM and longer-term outcome are avenues for future exploration which will help define the clinical relevance of the indicator.

Propylthiouracil-associated liver failure presenting as probable autoimmune hepatitis in a child with Graves' disease.

This case describes a young girl with Graves' disease, who presented with fulminant hepatic failure 9 months into propylthiouracil (PTU) therapy. Her clinical presentation was consistent with 'probable autoimmune hepatitis,' as defined by the International Autoimmune Hepatitis Group scoring system. Despite discontinuation of PTU and high-dose steroid therapy, she required liver transplantation. Subsequent pathology could not definitively rule out autoimmune hepatitis. PTU is an important cause of drug-related liver failure in children, and clinicians should be mindful that it is frequently used in patients who already have an underlying risk of autoimmune liver disease.