Lower risks of cirrhosis and hepatocellular carcinoma with GLP-1RAs in type 2 diabetes: A nationwide cohort study using target trial emulation framework.

BACKGROUND: To assess the association of cirrhosis and hepatocellular carcinoma (HCC) with the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs), which are the two commonly prescribed injectable glucose-lowering agents (GLAs) for patients with type 2 diabetes (T2D) after the failure of multiple oral GLAs. METHODS: We emulated a target trial using the nationwide data of a Taiwanese cohort with T2D. Incident new users of GLP-1RAs and LAIs during 2013-2018 were identified, and propensity score (PS) matching was applied to ensure between-group comparability in baseline patient characteristics. The primary outcome was the composite liver disease including cirrhosis or HCC. Each patient was followed until the occurrence of a study outcome, death, or the end of 2019, whichever came first. Subdistribution hazard models were employed to assess the treatment-outcome association. Sensitivity (e.g., stabilized inverse probability of treatment weighting analysis, time-dependent analysis), E-value, and negative control outcome analyses were performed to examine the robustness of study findings. RESULTS: We included 7171 PS-matched pairs of GLP-1RA and LAI users with no significant between-group differences at baseline. Compared with LAIs, the use of GLP-1RAs was associated with significantly reduced risks of composite liver disease (subdistribution hazard ratio [95% confidence interval]: 0.56 [0.42-0.76]), cirrhosis (0.59 [0.43-0.81]), and HCC (0.47 [0.24-0.93]). Results were consistent across sensitivity analyses and among patients with different baseline characteristics. CONCLUSION: Among T2D patients who require injectable GLAs, the use of GLP-1RAs versus LAIs was associated with lower risks of cirrhosis and HCC.

Safety and Efficacy of High-Dose Tranexamic Acid in Spine Surgery: A Retrospective Single-Institution Series.

OBJECTIVE: Currently, tranexamic acid (TXA) is the most widely used antifibrinolytic agent in spine surgery and has been proven to reduce perioperative blood loss. However, the safety of high-dose regimens remains in established. METHODS: A retrospective chart review was performed to identify all adult patients who underwent spine surgery with high-dose TXA (50 mg/kg loading dose, mg/kg/h maintenance dose) between September 2019 and March 2020. RESULTS: Thirty-six patients were treated with intraoperative high-dose TXA during the study period. The mean age was 56.6 (range: 22-82). Average body mass index was 27.2 (5.1) kg/m2. Average preoperative Charlson Comorbidity Index was 3.0 (2.7). The mean number of spinal levels operated on was 6.9 (4.3). Seven cases (19.4%) were revision surgeries. The mean intraoperative blood loss was 587.1 (900.0) mL, and total blood loss was 623.8 (991.9) mL. Postoperatively, time to ambulation was on average 1.7 (1.7) days. The mean total length of stay was 9.8 days (7.9, range 2-41). The most common indication for surgery was tumor (n = 9, 25%), followed by fracture (n = 8, 22.2%), deformity (n = 7, 19.4%), pseudarthrosis (n = 6, 16.7%), and symptomatic lumbar disc herniation (n = 2, 5.6%). There were no thromboembolic or other significant complications among the 36 patients. CONCLUSIONS: This retrospective case series demonstrates that the use of high-dose TXA provides is potentially safe and efficacious in adult patients undergoing complex spine surgeries. However, further investigations are required before the true safety and optimal dosing can be determined for high-dose TXA.

Cost-effectiveness of Novel Macrophage-Regulating Treatment for Wound Healing in Patients With Diabetic Foot Ulcers From the Taiwan Health Care Sector Perspective.

Importance: Diabetic foot ulcers (DFUs) and subsequent amputation incur enormous health and economic burdens to patients, health care systems, and societies. As a novel macrophage-regulating drug, ON101 is a breakthrough treatment for DFUs, which demonstrated significant complete wound healing effects in a phase 3 randomized clinical trial, but its economic value remains unknown. Objective: To assess the cost-effectiveness of an ON101 cream added on to general wound care (GWC; ie, conventional treatments for DFUs, which comprised initial and regular foot examinations, ulcer management, comorbidity control, patient education, and multidisciplinary care) vs GWC alone for DFUs from the Taiwan health care sector perspective. Design, Setting, and Participants: This economic evaluation used a hypothetical cohort of patients with diabetes, with characteristics mirroring those of the participants in the ON101 trial. A Markov state-transition simulation model was constructed to estimate costs and health outcomes associated with the ON101 with GWC and GWC alone strategies over a 5-year time horizon, discounting costs and effectiveness at 3% annually. Costs were in 2021 US dollars. Data were sourced from the ON101 trial and supplemented from published literature. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of input parameters and study generalizability. The analysis was designed and conducted from September 1, 2020, to January 31, 2022. Exposures: ON101 with GWC vs GWC alone. Main Outcomes and Measures: DFU-related complications, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Results: Patients in the hypothetical cohort had a mean age of 57 years and an uninfected DFU of 1 to 25 cm2 that was present for 4 or more weeks with a Wagner grade of 1 or 2. Over 5 years, the ON101 with GWC group vs the GWC alone group experienced more healing events, stayed for a longer time in the healing state, and had fewer infected DFUs, gangrene, and amputations (eg, 2787 additional healing events and 2766 fewer infected DFU, 72 fewer amputation, and 7 fewer gangrene events in the ON101 with GWC group vs GWC alone group). The ON101 with GWC strategy vs GWC alone yielded an additional 0.038 QALYs at an incremental cost of $571, resulting in $14 922/QALY gained. Economic results were most sensitive to healing efficacy, drug cost, and health utility of the healing state. Cost-saving results were observed in patient subgroups with poor glycemic control, larger ulcer sizes, longer ulcer durations, and current smoking. The ON101 with GWC strategy was considered cost-effective in 60% to 82% of model iterations against willingness-to-pay thresholds of $32 787/QALY gained to $98 361/QALY gained. Conclusions and Relevance: In this economic evaluation study using a simulated patient cohort, the ON101 with GWC strategy represented good value compared with GWC alone for patients with DFUs from the Taiwan health care sector perspective and may be prioritized for those with high risks for disease progression of DFUs.

Investigating Deep Brain Stimulation of the Habenula: A Review of Clinical Studies.

OBJECTIVES: The aim of this study was to examine the current scientific literature on deep brain stimulation (DBS) targeting the habenula for the treatment of neuropsychiatric disorders including schizophrenia, major depressive disorder, and obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: Two authors performed independent data base searches using the PubMed, Cochrane, PsycINFO, and Web of Science search engines. The data bases were searched for the query ("deep brain stimulation" and "habenula"). The inclusion criteria involved screening for human clinical trials written in English and published from 2007 to 2020. From the eligible studies, data were collected on the mean age, sex, number of patients included, and disorder treated. Patient outcomes of each study were summarized. RESULTS: The search yielded six studies, which included 11 patients in the final analysis. Treated conditions included refractory depression, bipolar disorder, OCD, schizophrenia, and major depressive disorder. Patients with bipolar disorder unmedicated for at least two months had smaller habenula volumes than healthy controls. High-frequency stimulation of the lateral habenula attenuated the rise of serotonin in the dorsal raphe nucleus for treating depression. Bilateral habenula DBS and patient OCD symptoms were reduced and maintained at one-year follow up. Low- and high-frequency stimulation DBS can simulate input paths to the lateral habenula to treat addiction, including cocaine addiction. More data are needed to draw conclusions as to the impact of DBS for schizophrenia and obesity. CONCLUSIONS: The habenula is a novel target that could aid in reducing neuropsychiatric symptoms and should be considered in circuit-specific investigation of neuromodulation for psychiatric disorders. More information needs to be gathered and assessed before this treatment is fully approved for treatment of neuropsychiatric conditions.

Utility of adding electrodes in patients undergoing invasive seizure localization: A case series.

Introduction: Surgery can be an effective treatment for epilepsy if the seizure onset is adequately localized. Invasive monitoring is used if noninvasive methods are inconclusive. Initial invasive monitoring may fail if the pre-surgical hypothesis regarding location of epileptic foci is wrong. At this point, a decision must be made whether to remove all electrodes without a clearly defined location of onset or to implant additional electrodes with the aim of achieving localization by expanding coverage. Methods: Electrodes were placed according to a hypothesis derived from noninvasive monitoring techniques in adult patients with long term epilepsy. Seizure onset was not clearly localized at the end of the invasive monitoring period in ten patients, and additional electrodes were placed based on a new hypothesis that incorporated data from the invasive monitoring period. Results: Successful localization was achieved in nine patients. There were no complications with adding additional electrodes. At final follow up, four patients were seizure free while four others had at least a 50% reduction in seizures after undergoing surgical intervention. Conclusion: Seizure foci were localized safely in 90% of adult patients with long term epilepsy after implanting additional electrodes and expanding coverage. Patients undergoing invasive monitoring without clear localization should have additional electrodes placed to expand monitoring coverage as it is safe and effective.

Supraorbital Keyhole Craniotomy in Pediatric Neurosurgery: A Systematic Review of Clinical Outcomes and Cosmetic Outcomes.

BACKGROUND: Supraorbital keyhole craniotomy is a minimally invasive approach used to access the parasellar region with advantages of decreased cortical exposure, simple closure, and decreased risk of postoperative cerebrospinal fluid leak. The incision of this approach, however, has raised cosmetic concerns, especially for pediatric patients. The aim of this study is to assess postoperative complications and cosmeses of the supraorbital keyhole approach for resection of intracranial lesions in pediatric patients. METHODS: A literature search of PubMed, Scopus, and Web of Science databases was performed on June 1, 2021, searching for all studies of pediatric patients undergoing supraorbital keyhole craniotomy for surgical resection of lesions in the anterior fossa/sellar region. RESULTS: Of 729 unique hits, 15 supraorbital keyhole studies reporting on 177 pediatric cases were included in the final review. Quality of all included studies was moderate. Overall, the surgery was well tolerated with a low number of severe adverse events. A wide variety of pathologies were treated with this approach. Complications of surgery included changes in vision, epidural hematoma, subdural hematoma, cerebrospinal fluid leak, and wound infection. At 6 weeks of follow-up, surgical scars in most patients were noted to be minimally detectable. At 3-6 months of follow-up, scars were no longer visible. Cosmetic complications included 5 bone defects, 1 split eyebrow, and 1 case of ptosis. CONCLUSIONS: This study suggests that supraorbital keyhole craniotomy is a safe and effective approach to access the parasellar region in pediatric patients with excellent cosmetic outcomes reported across multiple institutions.

Association of retinopathy severity with cardiovascular and renal outcomes in patients with type 1 diabetes: a multi-state modeling analysis.

This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan's National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients.

Three-step matching algorithm to enhance between-group comparability and minimize confounding in comparative effectiveness studies.

We developed a three-step matching algorithm to enhance the between-group comparability for comparative drug effect studies involving prevalent new-users of the newer study drug versus older comparator drug(s). The three-step matching scheme is to match on: (1) index date of initiating the newer study drug to align the cohort entry time between study groups, (2) medication possession ratio measures that consider prior exposure to all older comparator drugs, and (3) propensity scores estimated from potential confounders. Our approach is illustrated with a comparative cardiovascular safety study of glucagon-like peptide-1 receptor agonist (GLP-1ra) versus sulfonylurea (SU) in type 2 diabetes patients using Taiwan's National Health Insurance Research Database 2003-2015. 66% of 3195 GLP-1ra users had previously exposed to SU. The between-group comparability was well-achieved after implementing the matching algorithm (i.e., standardized mean difference < 0.2 for all baseline patient characteristics). Compared to SU, the use of GLP-1ra yielded a significantly reduced risk of the primary composite cardiovascular events (hazard ratio [95% confidence interval]: 0.71 [0.54-0.95], p = 0.022). Our matching scheme can enhance the between-group comparability in prevalent new-user cohort designs to minimize time-related bias, improve confounder adjustment, and ensure the reliability and validity of study findings.

Use of Tranexamic Acid for Elective Resection of Intracranial Neoplasms: A Systematic Review.

BACKGROUND: As an established antifibrinolytic agent, tranexamic acid (TXA) has garnered widespread use during surgery to limit intraoperative blood loss. In the field of neurosurgery, TXA is often introduced in cases of traumatic brain injury or elective spine surgeries; however, its role during elective cranial surgeries is not well established. We report a systematic review of the use of TXA in elective surgical resection of intracranial neoplasms. METHODS: We performed this systematic review following PRISMA guidelines to identify studies investigating the use of TXA in elective neurosurgical resection of intracranial neoplasms. Variables extracted included patient demographics, surgical indications, type of surgery performed, TXA dose and route of administration, operative duration, blood loss, transfusion rate, postoperative hemoglobin level, and complications. RESULTS: After careful screening, 4 articles (consisting of 682 patients) met our inclusion/exclusion criteria. The studies included 2 prospective cohort studies, 1 retrospective cohort study, and 1 case series. A χ2 test of pooled data demonstrated that patients administered TXA had a significantly decreased need for blood transfusions during surgery (odds ratio, 0.6273; 95% confidence interval, 0.4254-0.9251; P = 0.018). Mean total blood loss was 821.9 mL in the TXA group and 1099.0 mL in the control group across the studies. There was no significant difference in postoperative hemoglobin levels, with a mean of 11.4 g/dL in both the TXA and control groups. CONCLUSIONS: These results support the use of intraoperative TXA in tumor resection. However, its role in tumor resection has been less well investigated compared with its use in other areas of neurosurgery.

Citation analysis of the most influential ependymoma research articles illustrates improved knowledge of the molecular biology of ependymoma.

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, including a mix of basic science and clinical journals. The three institutions with the most papers in the top 100 were St. Jude Children's Research Hospital (16%), the University of Texas MD Anderson Cancer Center (6%), and the German Cancer Research Center (5%). We analyzed the publications that may be considered the most influential in the understanding and treatment management of ependymoma. Studies focused on the molecular classification of ependymomas were well-represented among the most cited articles, reflecting the field's current area of focus and its future directions. Additionally, this article also offers a reference for further studies in the ependymoma field.

Renoprotective effect of SGLT-2 inhibitors among type 2 diabetes patients with different baseline kidney function: a multi-center study.

BACKGROUND: To assess the effect of sodium glucose cotransporter-2 inhibitors (SGLT-2is) for type 2 diabetes on kidney outcomes stratified by patient baseline estimated glomerular filtration rate (eGFR) levels (i.e., eGFR ≤ 60, 60 < eGFR ≤ 90, and eGFR > 90 mL/min/1.73 m2). METHODS: Patients from three large healthcare delivery systems in Taiwan who had initiated SGLT-2is or other glucose-lowering drugs (oGLDs) between May 2016 and December 2017 were included. Main outcomes were the times to 30%, 40%, and 50% eGFR reduction after treatment initiation. One-to-one propensity score matching in the overall study cohort and in each eGFR subgroup between SGLT-2i and oGLD users was applied to ensure between-group comparability in baseline characteristics. RESULTS: There were 13,666 matched pairs of SGLT-2is and oGLD users in the overall cohort. While a sustained eGFR decline was revealed in oGLD-treated patients (mean values [standard errors] from 85.61 [0.43] to 82.49 [0.44] mL/min/1.73 m2 during the 12 months after treatment initiation), the mean eGFR values of SGLT-2i users decreased in the first 3 months (85.68 [0.37] to 79.71 [0.41] mL/min/1.73 m2) but then improved and sustained until the end of follow-up. There were 2300, 5705, and 5509 matched SGLT-2i and oGLD users in the eGFR ≤ 60, 60 < eGFR ≤ 90, and eGFR > 90 subgroups, respectively. Using SGLT-2is versus oGLDs was significantly associated with slower eGFR declines; hazard ratios (HRs) were 0.51 (95% CI 0.37-0.69), 0.51 (0.37-0.70), and 0.47 (0.31-0.71) for 40% eGFR reduction in the eGFR ≤ 60, 60 < eGFR ≤ 90, and eGFR > 90 subgroups, respectively. The renoprotective effect of SGLT-2is versus oGLDs was confirmed in the outcomes of 30% and 50% eGFR reduction across the three eGFR subgroups. CONCLUSIONS: This study supports the renoprotective benefit of real-world SGLT-2i use irrespective of patient baseline kidney function.

Long-term neurological and healthcare burden of adults with Japanese encephalitis: A nationwide study 2000-2015.

OBJECTIVE: To assess the healthcare utilization, economic burden, and long-term neurological complications and mortality of an adult population with Japanese encephalitis (JE). METHODS: This study utilized two nationwide datasets in Taiwan: the Notifiable Disease Dataset of confirmed cases from the Centers for Disease Control to identify JE patients, and the National Health Insurance Research Database to obtain patients' healthcare utilization. Survival analyses were performed to identify prognostic factors associated with the all-cause mortality of patients. RESULTS: This study included 352 adult cases with JE (aged≥20 years). The mean age of JE patients was 45 years. Stroke (event rate: 3.49/100 person-years) was the most common neurological complication, followed by epilepsy/convulsions (3.13/100 person-years), encephalopathy/delirium (2.20/100 person-years), and parkinsonism (1.97/100 person-years). Among the 336 hospitalized patients at JE diagnosis, 58.33% required intensive care. Among 79 patients who died following JE diagnosis, 48.84% of death events occurred within the year of diagnosis. The medical costs increased considerably at JE diagnosis and subsequent-year costs remained significantly higher than the costs before diagnosis (p<0.05). Having a four-dose JE vaccination (i.e., born after 1976) versus no JE vaccination history (i.e., born before 1963) was significantly associated with lower all-cause mortality (hazard ratio: 0.221 [95% confidence interval: 0.067, 0.725]). Comorbid diabetes and incident epilepsy/convulsion events significantly increased the mortality risk by 2.47- and 1.85-fold, respectively (p<0.05). CONCLUSION: A considerable medical burden associated with JE was observed in affected adults, even in the years following JE diagnosis. Vaccination should be considered to prevent this sporadic, but lethal, viral infection.

Comparison of Minimally Invasive Total versus Subtotal Resection of Spinal Tumors: A Systematic Review and Meta-Analysis.

OBJECTIVE: With the advent of minimally invasive techniques, minimally invasive spine surgery (MISS) has become a realistic option for many spine cases. This study aims to evaluate the operative and clinical outcomes of MISS for total versus subtotal tumor resection from current evidence. METHODS: A literature search was performed using the search term (Minimally invasive surgery OR MIS) AND (spine tumor OR spinal tumor). Studies including both minimally invasive total and subtotal resection cases with operative or clinical data were included. RESULTS: Seven studies describing 159 spinal tumor cases were included. Compared with total resection, subtotal resection showed no significant differences in surgical time (mean difference (MD), 9.44 minutes; 95% confidence interval [CI], -47.66 to 66.55 minutes; P = 0.37), surgical blood loss (MD, -84.72 mL; 95% CI, -342.82 to 173.39 mL; P = 0.34), length of stay (MD, 1.38 days; 95% CI, -0.95 to 3.71 days; P = 0.17), and complication rate (odds ratio, 9.47; 95% CI, 0.34-263.56; P = 0.12). Pooled analyses with the random-effects model showed that neurologic function improved in 89% of patients undergoing total resection, whereas neurologic function improved in 61% of patients undergoing subtotal resection. CONCLUSIONS: Our analyses show that there is no significant difference in operative outcomes between total and subtotal resection. Patients undergoing total resection showed slightly better improvement in neurologic outcomes compared with patients undergoing subtotal resection. Overall, this study suggests that both total and subtotal resection may result in comparable outcomes for patients with spinal tumors. However, maximal safe resection remains the ideal treatment because it provides the greatest chance of long-term benefit.

Ethical considerations and patient safety concerns for cancelling non-urgent surgeries during the COVID-19 pandemic: a review.

At the time of writing of this article, there have been over 110 million cases and 2.4 million deaths worldwide since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, postponing millions of non-urgent surgeries. Existing literature explores the complexities of rationing medical care. However, implications of non-urgent surgery postponement during the COVID-19 pandemic have not yet been analyzed within the context of the four pillars of medical ethics. The objective of this review is to discuss the ethics of elective surgery cancellation during the COVID-19 pandemic in relation to beneficence, non-maleficence, justice, and autonomy. This review hypothesizes that a more equitable decision-making algorithm can be formulated by analyzing the ethical dilemmas of elective surgical care during the pandemic through the lens of these four pillars. This paper's analysis shows that non-urgent surgeries treat conditions that can become urgent if left untreated. Postponement of these surgeries can cause cumulative harm downstream. An improved algorithm can address these issues of beneficence by weighing local pandemic stressors within predictive algorithms to appropriately increase surgeries. Additionally, the potential harms of performing non-urgent surgeries extend beyond the patient. Non-maleficence is maintained through using enhanced screening protocols and modifying surgical techniques to reduce risks to patients and clinicians. This model proposes a system to transfer patients from areas of high to low burden, addressing the challenge of justice by considering facility burden rather than value judgments concerning the nature of a particular surgery, such as cosmetic surgeries. Autonomy can be respected by giving patients the option to cancel or postpone non-urgent surgeries. However, in the context of limited resources in a global pandemic, autonomy is not absolute. Non-urgent surgeries can ethically be postponed in opposition to the patient's preference. The proposed algorithm attempts to uphold the four principles of medical ethics in rationing non-urgent surgical care by building upon existing decision models, using additional measures of resource burden and surgical safety to increase health care access and decrease long-term harm as much as possible. The next global health crisis will undoubtedly present its own unique challenges. This model may serve as a comprehensive starting point in determining future guidelines for non-urgent surgical care.

A nationwide cohort study for comparative vascular safety of long-acting insulin analogue versus intermediate-acting human insulin in type 2 diabetes.

Little is known about the comparative vascular safety of basal insulins (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes (T2D). This study sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with T2D. We utilized Taiwan's National Health Insurance Research Database to identify T2D patients who stably used IAHI (N = 11,521) or LAIA (N = 37,651) in the period 2004-2012. A rigorous three-step matching algorithm that considered the initiation date of basal insulin, previous exposure of antidiabetic treatments, comorbidities, diabetes severity and complications, and concomitant medications was applied to achieve the between-group comparability. Study outcomes, including cardiovascular diseases (CVDs), microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI] 1.20-2.67) and hospitalized hypoglycemia (aHR: 1.82; 95% CI 1.51-2.20), but a lower risk of composite MVDs (aHR: 0.88; 95% CI 0.84-0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. In summary, although the use of IAHI versus LAIA among T2D patients in usual practice may be associated with a lower risk of MVDs, strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population.

Cost-effectiveness of GLP-1 receptor agonists versus insulin for the treatment of type 2 diabetes: a real-world study and systematic review.

BACKGROUND: To conduct a real-word-study-based cost-effectiveness analysis of a GLP-1 receptor agonist (GLP-1RA) versus insulin among type 2 diabetes patients requiring intensified injection therapy and a systematic review of cost-effectiveness studies of GLP-1RAs versus insulin. METHODS: Individual-level analyses incorporating real-world effectiveness and cost data were conducted for a cohort of 1022 propensity-score-matched pairs of GLP-1RA and insulin users from Taiwan's National Health Insurance Research Database, 2007-2016. Study outcomes included the number needed to treat (NNT) to prevent one case of clinical events, healthcare costs, and cost per case of event prevented. Costs were in 2019 US dollars. Analyses were performed from a third-party payer and healthcare sector perspectives. Structured systematic review procedures were conducted to synthesize updated evidence on the cost-effectiveness of GLP-1RAs versus insulin. RESULTS: Over a mean follow-up of 2.3 years, the NNT using a GLP-1RA versus insulin to prevent one case of all-cause mortality and hospitalized hypoglycemia was 57 and 30, respectively. Using GLP-1RAs instead of insulin cost US$54,851 and US$29,115 per case of all-cause mortality and hospitalized hypoglycemia prevented, respectively, from the payer perspective, and saved US$19,391 and US$10,293, respectively, from the healthcare sector perspective. Sensitivity analyses showed that the probability of using GLP-1RAs versus insulin being cost-effective for preventing one case of all-cause mortality or hospitalized hypoglycemia ranged from 60 to 100%. The systematic review revealed a cost-effective profile of using GLP-1RAs versus insulin. CONCLUSIONS: Using GLP-1RAs versus insulin for type 2 diabetes patients requiring intensified injection therapy in clinical practice is cost-effective.

Pituitary spindle cell oncocytoma: illustrative case.

BACKGROUND: Spindle cell oncocytoma (SCO) of the pituitary gland is an extremely rare nonfunctional World Health Organization grade I tumor. SCOs are often misdiagnosed as nonfunctional pituitary adenomas on the basis of preoperative imaging. They are often hypervascular and locally adherent, which increases hemorrhage risk and limits resection, leading to increased risk of recurrence. The authors report a case of SCO treated at their institution and provide a review of the current literature. OBSERVATIONS: SCO of the pituitary gland can be a rare cause of progressively growing pituitary tumors that presents similarly to nonfunctional pituitary adenoma. Endoscopic transsphenoidal resection of the tumor by a multidisciplinary team allowed total resection despite local adherence of the tumor. Postoperatively, the patient's visual symptoms improved with persistence of secondary adrenal insufficiency and secondary hypothyroidism. LESSONS: Careful resection is needed due to SCO's characteristic hypervascularity and strong adherence to minimize local structure damage. Long-term follow-up is recommended due to the tendency for recurrence.

Hepatic and cardiovascular safety of acarbose among type 2 diabetes patients with end-stage renal disease: A nationwide population-based longitudinal study.

AIM: To assess the relationship between acarbose and hepatotoxicity, cardiovascular disease (CVD), and mortality among type 2 diabetes (T2D) patients with end-stage renal disease (ESRD). METHODS: 32,531 T2D patients with ESRD were identified from Taiwan's National Health Insurance Research Database in 2000~∼2012 and followed up until 2013. 19.3% of subjects were newly initiated with acarbose during the follow-up. The use of acarbose was quantified as the numbers of the 30-day drug's supplies and dosages (measured by defined daily doses; DDDs), respectively. Time-varying Cox models were applied to evaluate the association of acarbose use with hepatic, cardiovascular and mortality outcomes, with adjustment for patients' demographics, comorbidities, diabetes severity, and co-medications. RESULTS: For each 30-day supply increase in acarbose exposure, the risks of hepatic injury, composite CVD events, and all-cause mortality were significantly lowered by 9% (95% confidence interval: 6-12%), 7% (6-7%) and 7% (7-8%), respectively, while for each 30-day DDD increase in acarbose exposure, the risks for three aforementioned outcomes were significantly reduced by 45% (33-54%), 33% (29-36%) and 35% (32-39%), respectively. In subgroup analyses, the favorable study outcomes of acarbose use were more apparent among patients with more severe diabetes, a longer diabetes duration, or absence of established CVD at baseline. CONCLUSION: Acarbose used in real-world T2D patients with ESRD may have hepatic and cardiovascular safety.

Heterogeneous Treatment Effects on Cardiovascular Diseases With Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas in Type 2 Diabetes Patients.

This study explored heterogeneous treatment effects (HTEs) of the real-world use of dipeptidyl peptidase-4 inhibitors (DPP-4is) vs. sulfonylureas (SUs) on cardiovascular diseases (CVDs) and mortality in patients with type 2 diabetes. Utilizing Taiwan's National Health Insurance Research Database, 19,853 propensity score-matched pairs of DPP-4i and SU stable users were identified. Classification and regression tree analyses and Cox models were applied to explore HTEs, according to various patient characteristics, on the composite CVDs, three-point major adverse cardiovascular event (MACE), and all-cause mortality. The absolute risk difference (ARD), hazard ratio (HR), and 95% confidence interval (CI) were estimated for comparing treatment effects. CVD history, ischemic stroke, or transient ischemic attack (IS/TIA) history, and age at treatment initiation were significant treatment effect modifiers. Patients with prior IS/TIA but without any other prior CVDs benefited most in reduced risks of composite CVDs from using DPP-4i vs. SU (ARD -4.31%, 95% CI -7.48% to -1.14%, HR 0.81, 95% CI 0.69 ~ 0.95), followed by those without prior IS/TIA and CVDs and initiated with DPP-4i at age < 69.3 years (ARD -0.90%, 95% CI -1.47% to -0.32%, HR 0.86, 95% CI 0.77 ~ 0.97). Patients with prior IS/TIA benefited most in reduced risks of three-point MACE from using DPP-4i vs. SU (ARD -4.22%, 95% CV -6.66% to -1.78%, HR 0.80, 95% CI 0.69 ~ 0.93), followed by those without prior IS/TIA and initiated with DPP-4i at age < 69.3 years (ARD -0.68%, 95% CI -1.08% to -0.29%, HR 0.81, 95% CI 0.70 ~ 0.93). Consideration of CVD and IS/TIA histories and age could facilitate individualized diabetes management of using DPP-4i vs. SU. Future studies are warranted given the hypothesis-generating nature in this exploratory research.