Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder.

INTRODUCTION: Anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) is a complement-mediated autoimmune disease in which unpredictable and relapsing attacks on the central nervous system cause irreversible and accumulating damage. Comparative efficacy of new NMOSD therapies, such as ravulizumab, with established therapies is critical in making informed treatment decisions. METHODS: Efficacy of ravulizumab relative to established AQP4-Ab+ NMOSD treatments, such as eculizumab, inebilizumab, and satralizumab, was evaluated in a Bayesian network meta-analysis (NMA). Data were extracted from trials identified by a systematic literature review. The final evidence base consisted of 17 publications representing five unique and global studies (PREVENT, N-MOmentum, SAkuraSky, SAkuraStar, and CHAMPION-NMOSD). The primary endpoint was time-to-first relapse; other outcomes included annualized relapse rates (ARRs). RESULTS: For patients receiving monotherapy (monoclonal antibody only), ravulizumab was associated with a lower risk of relapse than inebilizumab (hazard ratio [HR] 0.09, 95% credible interval [CrI] 0.02, 0.57) or satralizumab (HR 0.08, 95% CrI 0.01, 0.55) and was comparable to eculizumab (HR 0.86, 95% Crl 0.16, 4.52). Ravulizumab + immunosuppressive therapy (IST) was associated with a lower risk of relapse than satralizumab + IST (HR 0.15, 95% CrI 0.03, 0.78); the comparison with eculizumab + IST suggested no difference. No patients treated with inebilizumab received background IST and were thus excluded from analysis. The ARR with ravulizumab monotherapy was 98% lower compared with inebilizumab (rate ratio [RR] 0.02, 95% Crl 0.00, 0.38) and satralizumab (RR 0.02, 95% Crl 0.00, 0.42) monotherapies. The ARR with ravulizumab ± IST showed the strongest treatment-effect estimates compared with other interventions. CONCLUSION: In the absence of head-to-head randomized controlled trials, NMA results suggest ravulizumab, a C5 inhibitor, is likely to be more effective in preventing NMOSD relapse in patients with AQP4-Ab+ NMOSD when compared with other treatments having different methods of action.

Anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, also called AQP4-Ab+ NMOSD, is a rare autoimmune disease that causes repeated episodes of symptoms such as blindness, arm/leg weakness, painful spasms, vomiting, and hiccups, among other symptoms. Each episode can cause nervous system damage to worsen, making it more difficult to recover back to regular abilities. Repeated episodes are likely to cause permanent damage, such as blindness and paralysis. Medical treatments that reduce episodes also reduce the damage and the chances symptoms will become permanent. One treatment, ravulizumab, is being studied to treat adults with AQP4-Ab+ NMOSD. This analysis looked at information from published clinical studies to compare ravulizumab with three other treatments (eculizumab, inebilizumab, and satralizumab) to determine how well each treatment reduced NMOSD episodes. There are no studies that have tested all four treatments in one study. Here, the treatments were compared by a method used to estimate the likelihood of a treatment being better than the others. While all four treatments successfully reduced episodes in their own studies, this analysis predicts that ravulizumab would likely be best in preventing episodes compared with inebilizumab or satralizumab when used alone or in combination with other immunosuppressive treatments. These findings, in consideration along with other relevant factors such as cost, safety, dosing delivery method, and frequency of treatment, may help doctors and patients decide what is the best treatment option for each individual patient to prevent attacks in adults with AQP4-Ab+ NMOSD.

The relationship between cardiorespiratory fitness and inhibitory control following acute stress: An ERP study.

Although the relationships among acute stress, cardiorespiratory fitness (CRF), and cognitive function have been examined, whether CRF is related to behavioral and neuroelectric indices of inhibitory control following acute stress remains unknown. The purpose of the current study was to investigate the combined influence of acute stress and CRF on inhibitory control. Participants, aged 20-30 years, were stratified into the Higher-Fit (n = 31) and the Lower-Fit (n = 32) groups, and completed a Stroop task following the modified Maastricht Acute Stress Test (MAST) in the stress condition and the sham-MAST in the non-stress condition, during which electroencephalography was recorded. Behavioral (i.e., response time and accuracy) and neuroelectric (N2 and P3b components of the event-related potential) outcomes of inhibitory control were obtained. While the Higher-Fit group demonstrated shorter response times and higher accuracy than the Lower-Fit group following both the MAST and the sham-MAST, they also exhibited selective benefits of acute stress on inhibitory control performance (i.e., decreased response times and diminished interference scores). CRF-dependent alterations in neuroelectric indices were also observed, with the Higher-Fit group displaying smaller N2 and greater P3b amplitudes than the Lower-Fit group following the sham-MAST, and increased N2 and attenuated P3b amplitudes following the MAST. Collectively, these findings not only confirm the positive relationship between CRF and inhibitory control but also provide novel insights into the potential influence of CRF on inhibitory control and associated neuroelectric activity following acute stress.

Silencing ANGPTL8 reduces mouse preadipocyte differentiation and insulin signaling.

ANGPTL8, expressed mainly in the liver and adipose tissue, regulates the activity of lipoprotein lipase (LPL) present in the extracellular space and triglyceride (TG) metabolism through its interaction with ANGPTL3 and ANGPTL4. Whether intracellular ANGPTL8 can also exert effects in tissues where it is expressed is uncertain. ANGPTL8 expression was low in preadipocytes and much increased during differentiation. To better understand the role of intracellular ANGPTL8 in adipocytes and assess whether it may play a role in adipocyte differentiation, we knocked down its expression in normal mouse subcutaneous preadipocytes. ANGPTL8 knockdown reduced adipocyte differentiation, cellular TG accumulation and also isoproterenol-stimulated lipolysis at day 7 of differentiation. RNA-Seq analysis of ANGPTL8 siRNA or control siRNA transfected SC preadipocytes on days 0, 2, 4 and 7 of differentiation showed that ANGPTL8 knockdown impeded the early (day 2) expression of adipogenic and insulin signaling genes, PPARγ, as well as genes related to extracellular matrix and NF-κB signaling. Insulin mediated Akt phosphorylation was reduced at an early stage during adipocyte differentiation. This study based on normal primary cells shows that ANGPTL8 has intracellular actions in addition to effects in the extracellular space, like modulating LPL activity. Preadipocyte ANGPTL8 expression modulates their differentiation possibly via changes in insulin signaling gene expression.

Cost-Effectiveness Analysis of PET-CT Surveillance After Treatment of Human Papillomavirus-Positive Oropharyngeal Cancer.

OBJECTIVE: To determine the cost-effectiveness of surveillance imaging with PET/CT scan among patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Oncologic care centers in the United States with head and neck oncologic surgeons and physicians. METHODS: We compared the cost-effectiveness of 2 posttreatment surveillance strategies: clinical surveillance with the addition of PET/CT scan versus clinical surveillance alone in human papillomavirus-positive oropharyngeal squamous cell carcinoma patients. We constructed a Markov decision model which was analyzed from a third-party payer's perspective using 1-year Markov cycles and a 30-year time horizon. Values for transition probabilities, costs, health care utilities, and their studied ranges were derived from the literature. RESULTS: The incremental cost-effectiveness ratio for PET/CT with clinical surveillance versus clinical surveillance alone was $89,850 per quality-adjusted life year gained. Flexible fiberoptic scope exams during clinical surveillance would have to be over 51% sensitive or PET/CT scan cost would have to exceed $1678 for clinical surveillance alone to be more cost-effective. The willingness-to-pay threshold at which imaging surveillance was equally cost-effective to clinical surveillance was approximately $80,000/QALY. CONCLUSION: Despite lower recurrence rates of human papillomavirus-positive oropharyngeal cancer, a single PET/CT scan within 6 months after primary treatment remains a cost-effective tool for routine surveillance when its cost does not exceed $1678. The cost-effectiveness of this strategy is also dependent on the clinical surveillance sensitivity (flexible fiberoptic pharyngoscopy), and willingness-to-pay thresholds which vary by country.

Head and Neck Injuries among Powered Scooter Users between 2010 and 2019.

Powered scooters, including electric scooters (e-scooters), have become an increasingly available and popular mode of personal transportation, but the health risks of these devices are poorly explored. We aim to quantify the increase in frequency of powered scooter-associated head and neck region injuries occurring yearly from 2010 to 2019, and to compare the frequency and severity of injury with those involving unpowered scooters. Here we present a retrospective cross-sectional study of all patients with head and neck injuries associated with powered and unpowered scooters seen in emergency departments reporting to the National Electronic Injury Surveillance System (NEISS) database from January 1, 2010 to December 31, 2019. During this time frame, a total of 1,620 injuries associated with powered scooters and a total of 5,675 injuries associated with unpowered scooters were reported to the NEISS. The database estimates these to reflect a nationwide total of 54,036 powered scooter-related injuries and 168,265 unpowered scooter-related injuries. Powered scooter injuries have increased for both children and adults since 2014, and estimated powered scooter injuries (16,243) surpassed estimated unpowered scooter injuries (14,124) when including all age groups for the first time in 2019. In 2019, adults are estimated to have nearly twice as many powered scooter-related head and neck injuries as children (10,884 vs. 5,359, respectively). In 2019, a higher proportion of powered scooter-related injuries involving adults were severe injuries when compared with those involving children (13.3 vs. 5.2%, respectively). Interestingly, unpowered scooters still cause many more estimated injuries in children than powered scooters did during 2019 (11,953 vs. 5,083). We find that powered scooters are now associated with a greater number and severity of head and neck injuries among the adult population than the pediatric population. But unpowered scooters still cause more head and neck injuries than powered scooters in the pediatric population.

Association of Intensive Lifestyle Intervention for Type 2 Diabetes With Labor Market Outcomes.

Importance: An intensive lifestyle intervention (ILI) has been shown to improve diabetes management and physical function. These benefits could lead to better labor market outcomes, but this has not been previously studied. Objective: To estimate the association of an ILI for weight loss in type 2 diabetes with employment, earnings, and disability benefit receipt during and after the intervention. Design, Setting, and Participants: This cohort study included participants with type 2 diabetes and overweight or obesity and compared an ILI with a control condition of diabetes support and education. Data for the original trial were accrued from August 22, 2001, to September 14, 2012. Trial data were linked with Social Security Administration records to investigate whether, relative to the control group, the ILI was associated with improvements in labor market outcomes during and after the intervention period. Difference-in-differences models estimating relative changes in employment, earnings, and disability benefit receipt between the ILI and control groups were used, accounting for prerandomization differences in outcomes for linked participants. Outcome data were analyzed from July 13, 2020, to May 17, 2023. Exposure: The ILI consisted of sessions with lifestyle counselors, dieticians, exercise specialists, and behavioral therapists on a weekly basis in the first 6 months, decreasing to a monthly basis by the fourth year, designed to achieve and maintain at least 7% weight loss. The control group received group-based diabetes education sessions 3 times annually during the first 4 years, with 1 annual session thereafter. Main Outcomes and Measures: Employment and receipt of federal disability benefits (Supplemental Security Income and Social Security Disability Insurance), earnings, and disability benefit payments from 1994 through 2018. Results: A total of 3091 trial participants were linked with Social Security Administration data (60.1% of 5145 participants initially randomized and 97.0% of 3188 of participants consenting to linkage). Among the 3091 with fully linked data, 1836 (59.4%) were women, and mean (SD) age was 58.4 (6.5) years. Baseline clinical and demographic characteristics were similar between linked participants in the ILI and control groups. Employment increased by 2.9 (95% CI, 0.3-5.5) percentage points for the ILI group relative to controls (P = .03) with no significant relative change in disability benefit receipt (-0.9 [95% CI, -2.1 to 0.3] percentage points; P = .13). Conclusions and Relevance: The findings of this cohort study suggest that an ILI to prevent the progression and complications of type 2 diabetes was associated with higher levels of employment. Labor market productivity should be considered when evaluating interventions to manage chronic diseases.

Novel insights into systemic sclerosis using a sensitive computational method to analyze whole-genome bisulfite sequencing data.

BACKGROUND: Abnormal DNA methylation is thought to contribute to the onset and progression of systemic sclerosis. Currently, the most comprehensive assay for profiling DNA methylation is whole-genome bisulfite sequencing (WGBS), but its precision depends on read depth and it may be subject to sequencing errors. SOMNiBUS, a method for regional analysis, attempts to overcome some of these limitations. Using SOMNiBUS, we re-analyzed WGBS data previously analyzed using bumphunter, an approach that initially fits single CpG associations, to contrast DNA methylation estimates by both methods. METHODS: Purified CD4+ T lymphocytes of 9 SSc and 4 control females were sequenced using WGBS. We separated the resulting sequencing data into regions with dense CpG data, and differentially methylated regions (DMRs) were inferred with the SOMNiBUS region-level test, adjusted for age. Pathway enrichment analysis was performed with ingenuity pathway analysis (IPA). We compared the results obtained by SOMNiBUS and bumphunter. RESULTS: Of 8268 CpG regions of ≥ 60 CpGs eligible for analysis with SOMNiBUS, we identified 131 DMRs and 125 differentially methylated genes (DMGs; p-values less than Bonferroni-corrected threshold of 6.05-06 controlling family-wise error rate at 0.05; 1.6% of the regions). In comparison, bumphunter identified 821,929 CpG regions, 599 DMRs (of which none had ≥ 60 CpGs) and 340 DMGs (q-value of 0.05; 0.04% of all regions). The top ranked gene identified by SOMNiBUS was FLT4, a lymphangiogenic orchestrator, and the top ranked gene on chromosome X was CHST7, known to catalyze the sulfation of glycosaminoglycans in the extracellular matrix. The top networks identified by IPA included connective tissue disorders. CONCLUSIONS: SOMNiBUS is a complementary method of analyzing WGBS data that enhances biological insights into SSc and provides novel avenues of investigation into its pathogenesis.

Severe Multifocal Placoid Chorioretinitis Associated with Immune Checkpoint Inhibitor Therapy.

PURPOSE: To report a case of severe bilateral multifocal placoid chorioretinitis in a patient receiving ipilimumab and nivolumab therapy for metastatic melanoma. METHODS: Retrospective, observational case report. RESULTS: A 31-year-old woman on ipilimumab and nivolumab for metastatic melanoma developed severe multifocal placoid chorioretinitis in both eyes. The patient was started on topical and systemic corticosteroid therapy and immune checkpoint inhibitor therapy was paused. Following resolution of ocular inflammation, the patient was restarted on immune checkpoint inhibitor therapy without return of ocular symptoms. CONCLUSION: Extensive multifocal placoid chorioretinitis may occur in patients undergoing immune checkpoint inhibitor (ICPI) therapy. Some patients with ICPI-related uveitis may successfully resume ICPI therapy under close collaboration with the treating oncologist.

Orbital Proptosis and Sinusitis in a Middle-aged Woman.

A 48-year-old woman presented with 3 days of worsening right orbital swelling, eye pain, blurry vision, and 3 months of bilateral photophobia, with rhinorrhea, congestion, and headaches. What is your diagnosis?

Safety and Efficacy of Propofol- and Ketamine-Based Procedural Sedation Regimen in Pediatric Patients During Burn Repetitive Dressing Change: 10 Years Single Center Experience.

It is crucial to provide an adequate level of sedation and analgesia during burn dressing changes in the pediatric population due to the amount of pain and anxiety patients experience during the procedure. To evaluate the safety and efficacy of an intensivist-based deep sedation regimen using a combination of propofol and ketamine to provide procedural sedation to pediatric burn patients. This is a retrospective chart review of pediatric patients who underwent inpatient burn wound dressing changes from 2011 through 2021. Demographic and clinical data, including age, length of the procedure, recovery time, medication doses, and adverse events, were collected. A total of 104 patients aged between 45 and 135 months with a median total burn body surface area (TBSA) of 11.5 percent (interquartile range [IQR] 4.0, 25.0) underwent 378 procedural sedation encounters with propofol- and ketamine-based sedation. The median total dose of propofol was 7 mg/kg (IRQ 5.3, 9.2). Of these sedations, 64 (17 percent) had minor adverse events, of which 50 (13 percent) were transient hypoxemia, 12 (3 percent) were upper airway obstruction, and 2 (0.5 percent) were hypotension. There were no serious adverse events. Hypoxemia was not related to age, weight, gender, burn TBSA, or total dose of propofol. There were 35 (33.6 percent) patients who had repetitive sedation encounters with no statistically significant changes in propofol dose or adverse events with the repeated encounters. Children can be effectively sedated for repetitive inpatient burn dressing changes. Given the high-risk patient populations, this procedure should be performed under the vigilance of highly trained providers.

DEXAMETHASONE INTRAVITREAL IMPLANT COMPLICATIONS INCLUDING VITREOUS HEMORRHAGE AND HYPOTONY.

PURPOSE: To describe cases of visually significant vitreous hemorrhage (VH) following dexamethasone intravitreal implant in our practice and present two cases that required surgical intervention and a case of VH and hypotony following dexamethasone implant. An injection technique that may minimize the incidence of these complications is described and illustrated. METHODS: Retrospective case series. RESULTS: The overall incidence of VH was 1.7% (8 of 467 injections) and those that required surgical intervention was 0.4% (2/467) over a 10-year period, from June 2010 to June 2020 ( Table 1 ). Overall, 75% (6 of 8) VH resolved spontaneously over time, without surgical intervention. CONCLUSION: Nonclearing VH and hypotony are rare but serious complications of dexamethasone implant.

Achieving tolerance modifies cancer susceptibility profiles in liver transplant recipients.

Long-term survival of transplant recipients is significantly impacted by malignancy. We aimed to determine whether calcineurin inhibitor (CNI)-treated recipients converted to and weaned off molecular target of rapamycin inhibitor (mTOR-I) therapy have favorable changes in their molecular profiles in regard to malignancy risk. We performed gene expression profiling from liver biopsy and blood (PBMC) specimens followed by network analysis of key dysregulated genes, associated diseases and disorders, molecular and cellular functions using IPA software. Twenty non-immune, non-viremic patients were included, and 8 of them achieved tolerance. Two comparisons were performed: (1) tolerance time point vs tacrolimus monotherapy and (2) tolerance time point vs sirolimus monotherapy. Upon achieving tolerance, IPA predicted significant activation of DNA damage response (p = 5.40e-04) and inhibition of DNA replication (p = 7.56e-03). Conversion from sirolimus to tolerance showed decrease in HCC (p = 1.30e-02), hepatic steatosis (p = 5.60e-02) and liver fibrosis (p = 2.91e-02) associated genes. In conclusion, this longitudinal study of patients eventually achieving tolerance reveals an evolving molecular profile associated with decreased cancer risk and improved hepatic steatosis and liver fibrosis. This provides a biological rationale for attempting conversion to mTOR-I therapy and tolerance following liver transplantation particularly in patients at higher risk of cancer incidence and progression post-transplant.

An overview of Internal Medicine Point-of-Care Ultrasound rotations in Canada.

BACKGROUND: Point-of-care ultrasound (POCUS) is a growing part of internal medicine training programs. Dedicated POCUS rotations are emerging as a particularly effective tool in POCUS training, allowing for longitudinal learning and emphasizing both psychomotor skills and the nuances of clinical integration. In this descriptive paper, we set out to review the state of POCUS rotations in Canadian Internal Medicine training programs. RESULTS: We identify five programs currently offering a POCUS rotation. These rotations are offered over two to thirteen blocks each year, run over one to four weeks and support one to four learners. Across all programs, these rotations are set up as a consultative service that offers POCUS consultation to general internal medicine inpatients, with some extension of scope to the hospitalist service or surgical subspecialties. The funding model for the preceptors of these rotations is predominantly fee-for-service using consultation codes, in addition to concomitant clinical work to supplement income. All but one program has access to hospital-based archiving of POCUS exams. Preceptors dedicate ten to fifty hours to the rotation each week and ensure that all trainee exams are reviewed and documented in the patient's medical records in the form of a consultation note. Two of the five programs also support a POCUS fellowship. Only two out of five programs have established learner policies. All programs rely on In-Training Evaluation Reports to provide trainee feedback on their performance during the rotation. CONCLUSIONS: We describe the different elements of the POCUS rotations currently offered in Canadian Internal Medicine training programs. We share some lessons learned around the elements necessary for a sustainable rotation that meets high educational standards. We also identify areas for future growth, which include the expansion of learner policies, as well as the evolution of trainee assessment in the era of competency-based medical education. Our results will help educators that are endeavoring setting up POCUS rotations achieve success.

Access to Disease-Modifying Alzheimer's Therapies: Addressing Possible Challenges Using Innovative Payment Models.

OBJECTIVES: Aduhelm is the first approved disease-modifying therapies (DMT) for Alzheimer disease (AD). Nevertheless, under current payment models, AD DMTs-especially because they treat broader populations-will pose challenges to patient access since costs may accrue sooner than benefits do. New payment approaches may be needed to address this difference in timing. METHODS: We use the Future Elderly Model that draws on nationally representative data sets such as the Health and Retirement Study to estimate the potential benefits because of hypothetical AD DMTs in 4 stylized treatment scenarios for patients with mild cognitive impairment or mild AD, and develop a payment model to estimate the accrual of net costs and benefits to private and public payers. RESULTS: The modeled AD DMTs result in clinical benefit of 0.30 to 0.55 quality-adjusted life-years gained per patient in the baseline treatment scenario and 0.13 to 0.24 quality-adjusted life-years gained per patient in the least optimistic scenario. Private payers may observe a net loss in patients at the age of 61 to 65 years under the status quo (payment upon treatment). Constant and deferred installment payment models resolve this issue. CONCLUSIONS: Innovative payment solutions, such as installment payments, may be required to address misaligned incentives that AD DMTs may create among patients younger than the age of 65 years and may help address concerns about the timing and magnitude of costs and benefits accrued to private payers.

Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials.

Introduction: The U.S. Food and Drug Administration (FDA)'s guidances help describe the agency's current thinking on regulatory issues and serve as a means of informal policymaking that is non-binding. This study examines the impact of two guidance documents for Alzheimer's disease (AD) trials. The first guidance in 2013 encouraged the use of cognitive/functional endpoints, while the second in 2018 modified such recommendation. Methods: Using pivotal trial data, we applied a regression discontinuity in time (RDiT) framework to examine trialist response to these guidance documents. Results were stratified by disease-modifying therapy (DMT) status, and controlled for disease staging, FDA registration status, and trial phase. Results: Among AD DMT trials, annual use of cognitive/functional composite endpoints significantly increased after the 2013 guidance (+12.9%, P < .001), and significantly decreased after the 2018 guidance (-19.9%, P = .022). Discussion: Although guidance documents do not set new legal standards or impose binding requirements, our findings indicate they are broadly followed by AD trialists.

Crosswalk between the Mini-Mental State Examination and the Telephone Interview for Cognitive Status (TICS-27/30/40).

BACKGROUND: We develop a crosswalk between the Mini-Mental State Examination (MMSE) and Telephone Interview for Cognitive Status (TICS)-27, TICS-30, and TICS-40 for adults 65 years and older. METHODS: We examined the scores of 1809 participants, with and without cognitive impairment, who completed the MMSE and the TICS assessment in the 2016 Health and Retirement Study and the 2016 Harmonized Cognitive Assessment Protocol study. Crosswalks between MMSE and TICS-27/30/40 were developed via equipercentile equating. RESULTS: We present crosswalks for MMSE and TICS-27/30/40 for the 65+ population representative of the US elderly. While monotonic, the pattern of the TICS-30 to MMSE crosswalk differs from the other two crosswalks (MMSE to TICS-27/40). CONCLUSION: Our analysis offers an empirical crosswalk between two commonly used cognitive measures-the MMSE and TICS. Our findings suggest the need for validated and robust measures that allow for the comparison of scores on different cognitive scales.

Cost-effectiveness Analysis of Submandibular Gland Preservation With Sialendoscopy for the Management of Sialolithiasis.

OBJECTIVE: To compare the cost-effectiveness of sialendoscopy with gland excision for the management of submandibular gland sialolithiasis. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Outpatient surgery centers. METHODS: A Markov decision model compared the cost-effectiveness of sialendoscopy versus gland excision for managing submandibular gland sialolithiasis. Surgical outcome probabilities were found in the primary literature. The quality of life of patients was represented by health utilities, and costs were estimated from a third-party payer's perspective. The effectiveness of each intervention was measured in quality-adjusted life-years (QALYs). The incremental costs and effectiveness of each intervention were compared, and a willingness-to-pay ratio of $150,000 per QALY was considered cost-effective. One-way, multivariate, and probabilistic sensitivity analyses were performed to challenge model conclusions. RESULTS: Over 10 years, sialendoscopy yielded 9.00 QALYs at an average cost of $8306, while gland excision produced 8.94 QALYs at an average cost of $6103. The ICER for sialendoscopy was $36,717 per QALY gained, making sialendoscopy cost-effective by our best estimates. The model was sensitive to the probability of success and the cost of sialendoscopy. Sialendoscopy must meet a probability-of-success threshold of 0.61 (61%) and cost ≤$11,996 to remain cost-effective. A Monte Carlo simulation revealed sialendoscopy to be cost-effective 60% of the time. CONCLUSION: Sialendoscopy appears to be a cost-effective management strategy for sialolithiasis of the submandibular gland when certain thresholds are maintained. Further studies elucidating the clinical factors that determine successful sialendoscopy may be aided by these thresholds as well as future comparisons of novel technology.

Impact of immunosuppression on incidence of post-transplant diabetes mellitus in solid organ transplant recipients: Systematic review and meta-analysis.

BACKGROUND: Solid organ transplantation is a life-saving intervention for end-stage organ disease. Post-transplant diabetes mellitus (PTDM) is a common complication in solid organ transplant recipients, and significantly compromises long-term survival beyond a year. AIM: To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM. METHODS: Two hundred and six eligible studies identified 75595 patients on Tacrolimus, 51242 on Cyclosporine and 3020 on Sirolimus. Random effects meta-analyses was used to calculate incidence. RESULTS: Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus (OR = 1.4 95%CI: 1.0-2.0) and sirolimus (OR = 1.8; 95%CI: 1.5-2.2) than with Cyclosporine. The overall incidence of PTDM at years 2-3 was 17% for kidney, 19% for liver and 22% for heart. The risk factors for PTDM most frequently identified in the primary studies were age, body mass index, hepatitis C, and African American descent. CONCLUSION: Tacrolimus tends to exhibit higher diabetogenicity in the short-term (2-3 years post-transplant), whereas sirolimus exhibits higher diabetogenicity in the long-term (5-10 years post-transplant). This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.