Screening for Prediabetes and Type 2 Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Type 2 diabetes is common and is a leading cause of morbidity and disability. Objective: To review the evidence on screening for prediabetes and diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through September 2019; references; and experts; literature surveillance through May 21, 2021. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when at least 3 similar studies were available. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: The review included 89 publications (N = 68 882). Two randomized clinical trials (RCTs) (25 120 participants) found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years. For harms (eg, anxiety or worry), the trials reported no significant differences between screening and control groups. For recently diagnosed (not screen-detected) diabetes, 5 RCTs (5138 participants) were included. In the UK Prospective Diabetes Study, health outcomes were improved with intensive glucose control with sulfonylureas or insulin. For example, for all-cause mortality the relative risk (RR) was 0.87 (95% CI, 0.79 to 0.96) over 20 years (10-year posttrial assessment). For overweight persons, intensive glucose control with metformin improved health outcomes at the 10-year follow-up (eg, all-cause mortality: RR, 0.64 [95% CI, 0.45 to 0.91]), and benefits were maintained longer term. Lifestyle interventions (most involving >360 minutes) for obese or overweight persons with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs; pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with improved intermediate outcomes, such as reduced weight, body mass index, systolic blood pressure, and diastolic blood pressure (pooled weighted mean difference, -1.7 mm Hg [95% CI, -2.6 to -0.8] and -1.2 mm Hg [95% CI, -2.0 to -0.4], respectively). Metformin was associated with a significant reduction in diabetes incidence (pooled RR, 0.73 [95% CI, 0.64 to 0.83]) and reduction in weight and body mass index. Conclusions and Relevance: Trials of screening for diabetes found no significant mortality benefit but had insufficient data to assess other health outcomes; evidence on harms of screening was limited. For persons with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes; for obese or overweight persons with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes.

Does This Adult Patient Have Hypertension?: The Rational Clinical Examination Systematic Review.

Importance: Office blood pressure (BP) measurements are not the most accurate method to diagnose hypertension. Home BP monitoring (HBPM) and 24-hour ambulatory BP monitoring (ABPM) are out-of-office alternatives, and ABPM is considered the reference standard for BP assessment. Objective: To systematically review the accuracy of oscillometric office and home BP measurement methods for correctly classifying adults as having hypertension, defined using ABPM. Data Sources: PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and DARE databases and the American Heart Association website (from inception to April 2021) were searched, along with reference lists from retrieved articles. Data Extraction and Synthesis: Two authors independently abstracted raw data and assessed methodological quality. A third author resolved disputes as needed. Main Outcomes and Measures: Random effects summary sensitivity, specificity, and likelihood ratios (LRs) were calculated for BP measurement methods for the diagnosis of hypertension. ABPM (24-hour mean BP ≥130/80 mm Hg or mean BP while awake ≥135/85 mm Hg) was considered the reference standard. Results: A total of 12 cross-sectional studies (n = 6877) that compared conventional oscillometric office BP measurements to mean BP during 24-hour ABPM and 6 studies (n = 2049) that compared mean BP on HBPM to mean BP during 24-hour ABPM were included (range, 117-2209 participants per analysis); 2 of these studies (n = 3040) used consecutive samples. The overall prevalence of hypertension identified by 24-hour ABPM was 49% (95% CI, 39%-60%) in the pooled studies that evaluated office measures and 54% (95% CI, 39%-69%) in studies that evaluated HBPM. All included studies assessed sensitivity and specificity at the office BP threshold of 140/90 mm Hg and the home BP threshold of 135/85 mm Hg. Conventional office oscillometric measurement (1-5 measurements in a single visit with BP ≥140/90 mm Hg) had a sensitivity of 51% (95% CI, 36%-67%), specificity of 88% (95% CI, 80%-96%), positive LR of 4.2 (95% CI, 2.5-6.0), and negative LR of 0.56 (95% CI, 0.42-0.69). Mean BP with HBPM (with BP ≥135/85 mm Hg) had a sensitivity of 75% (95% CI, 65%-86%), specificity of 76% (95% CI, 65%-86%), positive LR of 3.1 (95% CI, 2.2-4.0), and negative LR of 0.33 (95% CI, 0.20-0.47). Two studies (1 with a consecutive sample) that compared unattended automated mean office BP (with BP ≥135/85 mm Hg) with 24-hour ABPM had sensitivity ranging from 48% to 51% and specificity ranging from 80% to 91%. One study that compared attended automated mean office BP (with BP ≥140/90 mm Hg) with 24-hour ABPM had a sensitivity of 87.6% (95% CI, 83%-92%) and specificity of 24.1% (95% CI, 16%-32%). Conclusions and Relevance: Office measurements of BP may not be accurate enough to rule in or rule out hypertension; HBPM may be helpful to confirm a diagnosis. When there is uncertainty around threshold values or when office and HBPM are not in agreement, 24-hour ABPM should be considered to establish the diagnosis.

Overall Work and Practice Satisfaction of Licensed Clinical Social Workers in the National Health Service Corps Loan Repayment Program.

Little is known about the job satisfaction of licensed clinical social workers (LCSWs) participating in the National Health Service Corps (NHSC) federal Loan Repayment Program (LRP). Employee satisfaction in organizations is important for organizational well-being and to decrease turnover. A satisfied NHSC LCSW workforce is also important given the array of services it provides, especially in rural and underserved areas. This study examined the work satisfaction of 386 LCSWs participating in the NHSC LRP in 21 states. Rural upbringing, being older than 40 years, and a higher salary were significantly associated with overall work and practice satisfaction. In addition, satisfaction with administration, staff and the practices' linkages to other health providers, the mission of the practice, and connection with patients were strongly associated with overall work and practice satisfaction. To our knowledge, this is the first study to examine the work and practice satisfaction of LCSWs participating in the NHSC LRP, and our findings have the potential to inform the NHSC's strategies in managing and retaining LCSWs.

Trends in Total and Out-of-Pocket Expenditures for Visits to Primary Care Physicians, by Insurance Type, 2002-2017.

PURPOSE: Total and out-of-pocket visit expenditures for primary care physician visits may affect how primary care is delivered. We determined trends in these expenditures for visits to US primary care physicians. METHODS: Using the 2002-2017 Medical Expenditure Panel Survey, we ascertained changes in total and out-of-pocket visit expenditures for primary care visits for Medicare, Medicaid, and private insurance. We calculated mean values for each insurer using a generalized linear model and a 2-part model, respectively. RESULTS: Analyses were based on 750,837 primary care visits during 2002-2017. Over time, the proportion of primary care visits associated with private insurance or no insurance decreased, while Medicare- or Medicaid-associated visits increased. The proportion of visits with $0 out-of-pocket expenditure increased, primarily from an increase in $0 private insurance visits. Total expenditure per visit increased for private insurance and Medicare visits, but did not notably change for Medicaid visits. Out-of-pocket expenditures rose primarily from increases in private insurance visits with higher expenditures of this type. Medicare and Medicaid had minimal change in out-of-pocket expenditure per visit. CONCLUSIONS: Between 2002 and 2017, mean total expenditures and out-of-pocket expenditures increased for primary care visits, but at notably lower rates than those previously documented for emergency department visits. A rise in total expenditure per visit was identified for private insurance and Medicare, but not for Medicaid. Out-of-pocket expenditures increased marginally related to changes in out-of-pocket expenditures for private insurance visits. We would expect increasing difficulty with primary care physician access, particularly for Medicaid patients, if the current trends continue.

Emergency Department Out-of-Pocket Expenditures by Insurance, 1999 to 2016.

STUDY OBJECTIVE: Per visit, emergency department (ED) expenditures have increased more for private insurance than Medicare and Medicaid during the past 20 years, but it is unknown whether ED out-of-pocket expenditures show a similar pattern of increase. We compare increases in per-visit ED out-of-pocket expenditures over time for visits that did not result in hospitalization or observation admissions for private insurance, Medicare, and Medicaid. METHODS: This repeated cross-sectional analysis of out-of-pocket expenditures used data from the 1999 to 2016 Medical Expenditure Panel Survey, a nationally representative survey of the noninstitutionalized US civilian population. We used 2-part models-logistic regression followed by a generalized linear model with a γ distribution and a log link function-to compare per-visit out-of-pocket expenditures over time among different payers. Models contained insurance type, year, an interaction between year and insurance type, region of country, sex, and 5 visit-level variables (magnetic resonance imaging/computed tomography scans, ultrasonography, surgical procedures, radiographs, and ECGs). RESULTS: In our sample of 107,519 ED visits, mean annual per-visit out-of-pocket expenditures increased $7.31 a year (95% confidence interval $6.22 to $8.41) for private insurance and did not increase for Medicare or Medicaid. Most private insurance and Medicare visits had out-of-pocket expenditures less than $100 and nearly all Medicaid visits had no out-of-pocket expenditures. There was no strong evidence suggesting that out-of-pocket expenditures at different total expenditure amounts increased appreciably for private insurance. CONCLUSION: Per-visit out-of-pocket expenditure increases for private insurance ED visits were predominantly related to overall increases in per-visit total expenditure.

Screening for Atrial Fibrillation With Electrocardiography: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation is the most common arrhythmia and increases the risk of stroke. Objective: To review the evidence on screening for nonvalvular atrial fibrillation with electrocardiography (ECG) and stroke prevention treatment in asymptomatic adults 65 years or older to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through June 6, 2018. Study Selection: English-language randomized clinical trials (RCTs), prospective cohort studies evaluating detection rates of atrial fibrillation or harms of screening, and systematic reviews evaluating stroke prevention treatment. Eligible treatment studies compared warfarin, aspirin, or novel oral anticoagulants (NOACs) with placebo or no treatment. Studies were excluded that focused on persons with a history of cardiovascular disease. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. When at least 3 similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Detection of previously undiagnosed atrial fibrillation, mortality, stroke, stroke-related morbidity, and harms. Results: Seventeen studies were included (n = 135 300). No studies evaluated screening compared with no screening and focused on health outcomes. Systematic screening with ECG identified more new cases of atrial fibrillation than no screening (absolute increase, from 0.6% [95% CI, 0.1%-0.9%] to 2.8% [95% CI, 0.9%-4.7%] over 12 months; 2 RCTs, n = 15 803), but a systematic approach using ECG did not detect more cases than an approach using pulse palpation (2 RCTs, n = 17 803). For potential harms, no eligible studies compared screening with no screening. Warfarin (mean, 1.5 years) was associated with a reduced risk of ischemic stroke (relative risk [RR], 0.32 [95% CI, 0.20-0.51]) and all-cause mortality (RR, 0.68 [95% CI, 0.50-0.93]) and with increased risk of bleeding (5 trials, n = 2415). Participants in treatment trials were not screen detected, and most had long-standing persistent atrial fibrillation. A network meta-analysis reported that NOACs were associated with a significantly lower risk of a composite outcome of stroke and systemic embolism (adjusted odds ratios compared with placebo or control ranged from 0.32-0.44); the risk of bleeding was increased (adjusted odds ratios, 1.4-2.2), but confidence intervals were wide and differences between groups were not statistically significant. Conclusions and Relevance: Although screening with ECG can detect previously unknown cases of atrial fibrillation, it has not been shown to detect more cases than screening focused on pulse palpation. Treatments for atrial fibrillation reduce the risk of stroke and all-cause mortality and increase the risk of bleeding, but trials have not assessed whether treatment of screen-detected asymptomatic older adults results in better health outcomes than treatment after detection by usual care or after symptoms develop.

The safety of resection for primary central nervous system lymphoma: a single institution retrospective analysis.

Surgical resection is not the standard of care for primary central nervous system lymphoma (PCNSL), as historical studies have demonstrated unfavorable complication rates and limited benefits. Some recent studies suggest that resection may provide a therapeutic benefit, yet the safety of these procedures has not been systematically investigated in the setting of modern neurosurgery. We examined the safety of surgical resection for PCNSL. We retrospectively analyzed all patients with PCNSL treated at Columbia University Medical Center between 2000 and 2015 to assess complications rates following biopsy or resection using the Glioma Outcomes Project system. We identified predictors of complications and selection for resection. Well-validated scales were used to quantify patients' baseline clinical characteristics, including functional status, comorbid disease burden, and cardiac risk. The overall complication rate was 17.2% after resection, and 28.2% after biopsy. Cardiac risk (p = 0.047, OR 1.72 [1.01, 2.95]), and comorbid diagnoses (p = 0.004, OR 3.05 [1.42, 6.57]) predicted complications on multivariable regression. Patients who underwent resection had better KPS scores (median 70 v. 80, p = 0.0068, ∆ 10 [0.0, 10.00]), and were less likely to have multiple (46.5% v. 27.6%, p = 0.030, OR 1.42 [1.05, 1.92]) or deep lesions (70.4% v. 39.7%, p = 0.001, OR 1.83 [1.26, 2.65]). Age (p = 0.048, OR 0.75 per 10-year increase [0.56, 1.00]) and deep lesions (p = 0.003, OR 0.29 [0.13, 0.65]) influenced selection for resection on multivariable regression. Surgical resection of PCNSL is safe for select patients, with complication rates comparable to rates for other intracranial neoplasms. Whether there is a clinical benefit to resection cannot be concluded.

MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.

Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and nonneoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-sequencing (RNA-seq) and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the The Cancer Genome Atlas dataset showed that the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples from the NE regions predominantly resembled the neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from nonneoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type-specific alterations varied between the different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes. These subtype-specific patterns provide new insights into molecular and cellular composition of the infiltrative margins of GBM.

Nontraumatic symptomatic de novo arachnoid cyst in an adolescent patient treated with cystoperitoneal shunting: illustrative case.

BACKGROUND: Arachnoid cysts are often congenital, asymptomatic lesions detected in the pediatric population. When seen in adults, they usually occur following trauma. De novo formation of arachnoid cysts is uncommon, with only a few instances cited in the literature and most of which occurred in the pediatric population. Treatment options for these lesions include observation, craniotomy for cyst resection, microsurgical/endoscopic fenestration, or shunting. OBSERVATIONS: In this report, the authors describe a female patient with a de novo, symptomatic, enlarging middle cranial fossa arachnoid cyst detected at age 16 years. She was treated with the placement of a cystoperitoneal shunt. After surgery, she experienced clinical and radiological improvement. LESSONS: We illustrate successful shunting of a de novo arachnoid cyst in a symptomatic teen patient. Although arachnoid cysts in certain intracranial locations are more likely to produce symptoms, those in the middle cranial fossa tend to be asymptomatic. To our knowledge, this is the first reported case of a symptomatic de novo arachnoid cyst located in the middle cranial fossa in a postpubertal patient. Although the current presentation is rare, the authors demonstrate an effective surgical treatment of a symptomatic, large, de novo arachnoid cyst in a postpubertal pediatric patient.

Murine cell line model of proneural glioma for evaluation of anti-tumor therapies.

Molecular subtypes of glioblastoma (GBM) with distinct alterations have been identified. There is need for reproducible, versatile preclinical models that resemble specific GBM phenotypes to facilitate preclinical testing of novel therapies. We present a cell line-based murine proneural GBM model and characterize its response to radiation therapy. Proneural gliomas were generated by injecting PDGF-IRES-Cre retrovirus into the subcortical white matter of adult mice that harbor floxed tumor suppressors (Pten and p53) and stop-floxed reporters. Primary cell cultures were generated from the retrovirus induced tumors and maintained in vitro for multiple passages. RNA sequencing-based expression profiling of the resulting cell lines was performed. The tumorigenic potential of the cells was assessed by intracranial injection into adult naïve mice from different strains. Tumor growth was assessed by bioluminescence imaging (BLI). BLI for tumor cells and brain slices were obtained and compared to in vivo BLI. Response to whole-brain radiation was assessed in glioma-bearing animals. Intracranial injection of Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) glioma cells led to formation of GBM-like tumors with 100 % efficiency (n = 48) and tumorigenesis was retained for more than 3 generations. The cell lines specifically resembled proneural GBM based on expression profiling by RNA-Seq. Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) cell number correlated with BLI signal. Serial BLI measured tumor growth and correlated with size and location by ex vivo imaging. Moreover, BLI predicted tumor-related mortality with a 93 % risk of death within 5 days following a BLI signal between 1 × 10(8) and 5 × 10(8) photons/s cm(2). BLI signal had transient but significant response following radiotherapy, which corresponded to a modest survival benefit for radiated mice (p < 0.05). Intracranial injection of Pdgf(+)Pten(-/-)p53(-/-)luciferase(+) cells constitutes a novel and highly reproducible model, recapitulating key features of human proneural GBM, and can be used to evaluate tumor-growth and response to therapy.

Association of ≥ 12 months of delayed surgical treatment for cervical myelopathy with worsened postoperative outcomes: a multicenter analysis of the Quality Outcomes Database.

OBJECTIVE: Degenerative cervical myelopathy (DCM) results in significant morbidity. The duration of symptoms prior to surgical intervention may be associated with postoperative surgical outcomes and functional recovery. The authors' objective was to investigate whether delayed surgical treatment for DCM is associated with worsened postoperative outcomes. METHODS: Data from 1036 patients across 14 surgical centers in the Quality Outcomes Database were analyzed. Baseline demographic characteristics and findings of preoperative and postoperative symptom evaluations, including duration of symptoms, were assessed. Postoperative functional outcomes were measured using the Neck Disability Index (NDI) and modified Japanese Orthopaedic Association (mJOA) scale. Symptom duration was classified as either less than 12 months or 12 months or greater. Univariable and multivariable regression were used to evaluate for the associations between symptom duration and postoperative outcomes. RESULTS: In this study, 513 patients (49.5%) presented with symptom duration < 12 months, and 523 (50.5%) had symptoms for 12 months or longer. Patients with longer symptom duration had higher BMI and higher prevalence of anxiety and diabetes (all p < 0.05). Symptom duration ≥ 12 months was associated with higher average baseline NDI score (41 vs 36, p < 0.01). However, improvements in NDI scores from baseline were not significantly different between groups at 3 months (p = 0.77) or 12 months (p = 0.51). Likewise, the authors found no significant differences between groups in changes in mJOA scores from baseline to 3 months or 12 months (both p > 0.05). CONCLUSIONS: Surgical intervention resulted in improved mJOA and NDI scores at 3 months, and this improvement was sustained in both patients with short and longer initial symptom duration. Patients with DCM can still undergo successful surgical management despite delayed presentation.

Effect of systemic parathyroid hormone (1-34) and a beta-tricalcium phosphate biomaterial on local bone formation in a critical-size rat calvarial defect model.

OBJECTIVE: The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1-34) (PTH), a surgically implanted synthetic beta-tricalcium phosphate (beta-TCP) bone biomaterial serving as a matrix to support new bone formation. MATERIALS AND METHODS: Critical-size, 8 mm, calvarial through-and-through osteotomy defects were surgically created in 100 adult male Sprague-Dawley rats. The animals were randomized into five groups of 20 animals each to receive one of the following treatments: PTH (15 microg PTH/kg/day; subcutaneously), PTH/beta-TCP, beta-TCP, or particulate human demineralized freeze-dried bone (DFDB), and sham-surgery controls. Ten animals/group were euthanized at 4 and 8 weeks post-surgery for radiographic and histometric analysis. RESULTS: The histometric analysis showed that systemic PTH significantly enhanced local bone formation, bone fill averaging (+/-SE) 32.2+/-4.0% compared with PTH/beta-TCP (15.7+/-2.4%), beta-TCP (12.5+/-2.3%), DFDB (14.5+/-2.3%), and sham-surgery control (10.0+/-1.5%) at 4 weeks (p<0.014). Systemic PTH showed significantly enhanced bone formation (41.5+/-4.0%) compared with PTH/beta-TCP (22.4+/-3.0%), beta-TCP (21.3+/-4.4%), and with the sham-surgery control (23.8+/-4.2%) at 8 weeks (p<0.025). The DFDB group showed significantly increased bone formation from 4 (14.5+/-2.3%) to 8 weeks (32.0+/-3.2%) (p<0.006). The PTH/beta-TCP and beta-TCP groups both showed limited biomaterials resorption. The radiographic analysis was not diagnostic to distinguish local bone formation from the radiopaque beta-TCP biomaterial. CONCLUSIONS: Systemic administration of PTH significantly stimulates local bone formation. Bone formation was significantly limited by the beta-TCP biomaterial.

The effect of pulsed lavage irrigation on suture knot security.

PURPOSE: The purpose of this study was to determine the effect of low-pressure and pulsed lavage irrigation on suture knot security. METHODS: Ninety-tied suture loops were measured for baseline circumference and then subjected to no irrigation, bulb syringe irrigation, or pulsed lavage irrigation. The sutures were placed under a load and then measured for final circumference. A larger circumference difference indicated poorer knot security. RESULTS: There was a statistically significant difference in the knot security between all three groups (p < 0.001). Pulsed lavage resulted in the greatest circumference increase (0.52 ± 0.19 mm), followed by bulb syringe (0.24 ± 0.18 mm), and lastly no irrigation (0.08 ± 0.00 mm). None of the groups had any catastrophic failures. No knots met the predetermined criteria for knot failure. CONCLUSION: Pulsed lavage irrigation resulted in a statistically significant decrease in suture knot security as compared to bulb syringe irrigation and no irrigation. None of the groups met the currently accepted criteria for clinical suture failure, which has a relatively arbitrary value. While the available literature does not discuss increases in loop circumference for specific orthopedic applications, this small difference suggests that pulse lavage is unlikely to have a clinically significant impact on the suture integrity for most orthopedic procedures.

Thyroid Hormone Use in the United States, 1997-2016.

BACKGROUND: Thyroid disorders are among the most commonly treated conditions by the United States health care system. The number of patients reporting thyroid hormone use has increased in recent years, but it is unknown if there have been differential increases in the number of treated individuals within different demographic groups. Previous research has also not evaluated how expenditures for different thyroid hormone medications have changed in recent years. METHODS: Using data from the 1997 through 2016 Medical Expenditure Panel Survey, we calculated the proportion of adults reporting thyroid hormone prescriptions by 3 demographic variables (age, sex, and race) and determined expenditures from thyroid hormone prescriptions by medication type (overall, generic, Synthroid or Cytomel, and other brand). RESULTS: Between 1997 and 2016, the proportion of adults who reported thyroid hormone use increased from 4.1% (95% CI, 3.7-4.4) to 8.0% (95% CI, 7.5-8.5). Most of the growth in thyroid hormone use occurred among adults aged >65, and use was also more common among females and non-Hispanic whites. Expenditures from thyroid hormones increased from $1.1 billion (95% CI, 0.9-1.3) in 1997 to $3.2 billion dollars (95% CI, 2.9-3.6) in 2016. Generic thyroid hormone prescriptions comprised 18.1% of all thyroid hormone prescriptions in 2004 (95% CI, 15.8-20.4) and 80.8% of all thyroid hormone prescriptions (95% CI, 78.4-83.2) in 2016. CONCLUSIONS: Thyroid hormone use nearly doubled over the last 20 years, and increased use was associated with being older, female, and non-Hispanic white. During the same time period, thyroid hormone expenditures almost tripled.

Endoscopic Evacuation of a Panhemispheric Subdural Empyema.

BACKGROUND: Subdural empyema (SDE) is a well-known entity in pediatric populations and is associated with a high rate of morbidity and mortality. Large scale evacuation of empyema, although effective, places the bone flap at risk of failure when replaced. CASE DESCRIPTION: We report the case of a 19-year-old man with a history of a shunted left middle fossa cyst presenting with a panhemispheric SDE after removal of his cystoperitoneal shunt by an outside facility. Extensive evacuation was performed via the patients prior parietal shunt incision after expansion of the preexisting burr hole. Cultures grew methicillin-sensitive Staphylococcus aureus and Propionibacterium acnes, and he was treated with long-term antibiotics. The patient had a complete recovery with persistent empyema resolution on 6-month follow-up. CONCLUSIONS: Endoscopic-assisted burr hole evacuation of large panhemispheric and loculated SDE is feasible, effective, and safe. The primary advantage over conventional open evacuations is that it negates the need for a bone flap and its potential complications related to a secondary infection.

Anti-Hypertensive Medication Combinations in the United States.

BACKGROUND: Examining the anti-hypertensive regimens of individuals with different comorbidities may offer insights into how we can improve hypertension management. METHODS: The Medical Expenditure Panel Survey (2013-2015) was used to describe the most common single-, two-, three-, and four-drug hypertension regimens among hypertensive adults in four different comorbidity groups: 1. Hypertension only; 2. Hypertension and diabetes; 3. Hypertension and cardiovascular disease (coronary heart disease or stroke history); and 4. Hypertension, diabetes, and cardiovascular disease. RESULTS: 15,901 adults with hypertension taking anti-hypertensive medications were included in the study. 58.6% (95% CI: 57.3-59.8) took multiple anti-hypertensive medications, but the proportion of adults taking multiple anti-hypertensives varied by comorbidity group. Regimens including an ACE-inhibitor/ARB were the most prevalent regimens among individuals taking ≥2 anti-hypertensive medications. The most common two-drug regimen for both the hypertension-only and hypertension-diabetes groups was an ACE-inhibitor/ARB with thiazide. The most prevalent regimen for the two cardiovascular disease groups was an ACE-inhibitor/ARB with beta-blocker. CONCLUSIONS: Most individuals with hypertension use between 2-5 medications and the medications comprising these regimens vary by comorbidity. The ACCOMPLISH trial suggested that certain combinations may lead to superior cardiovascular outcomes. Research comparing the efficacy of different hypertension medication combinations among individuals with different comorbidities could lead to better patient hypertensionrelated outcomes.

The Utility of Using Preoperative MRI as a Predictor for Intraoperative Pituitary Adenoma Consistency and Surgical Resection Technique.

Objective Most pituitary adenomas are of soft consistency and can be resected during surgery with routine suction instruments. However, fibrous adenomas may require more aggressive techniques. The ability to predict consistency on magnetic resonance imaging (MRI) would improve preoperative preparation and may have implications on the extent of resection. Design A retrospective review of MRI and tumor histology of 50 consecutive patients who underwent endoscopic endonasal resection for nonfunctional adenomas was performed. Methods An intensity ratio was calculated based on quantitative MRI signal intensity of the adenoma and pons. Intraoperatively, a sequentially graded technique required for resection ranged from suction (R1) for softer tumors, curettes (R2) for tumors with intermediate consistency, and aspirators and/or other microinstruments (R3) for firmer tumors. Fibrotic content was determined from histologic collagen percentage, and rates of gross total resection (GTR) were calculated from postoperative imaging. Statistical analyses were performed to determine if resection classification could be predicted by intensity ratio or collagen percentage, calculate ratio of cut-off points for clinical use, and assess for correlation between intensity ratios and collagen percentage. Results Tumors with ratios < 1.6 on the T2-weighted coronal image and collagen content > 5.3% were likely to have required a more aggressive resection technique. Statistically significant lower rates of GTR and higher rates of perioperative complications were seen with such tumors. Conclusion Preoperative MRI analyses can be helpful but not definitive in predicting adenoma consistency. Fibrous adenomas, associated with higher collagen content, are more difficult to resect and have higher rates of subtotal resection.

Caudal Homeobox Gene-2 Staining Defines Intracranial Mature Teratoma with Differentiation to Colonic Adenocarcinoma.

BACKGROUND: Malignant transformation of a mature intracranial teratoma into an adenocarcinoma is an extremely rare event and portends a poor prognosis. The clinical progression, radiographic changes, histopathological findings, and immunohistochemistry findings from these unique cases might provide clues regarding this transformation. Caudal homeobox gene-2 (CDX-2) is a specific and robust marker for colonic adenocarcinomas and can also be used to identify differentiation of mature intracranial teratoma into colonic-type adenocarcinoma. To the best of our knowledge, this is the first case report of the use of this specific marker for an intracranial malignancy. CASE DESCRIPTION: We present the case of a 55-year-old right-handed Hispanic-American woman with progressive headaches who was found to have a left posterior parietotemporal tumor with intraventricular extension. Surgical debulking was performed, and the pathologic examination revealed a mature teratoma. Despite surgical resection and radiotherapy, the teratoma progressed to a malignant mature intracranial teratoma both radiographically and histologically. Histological analysis of the third specimen revealed a moderately differentiated adenocarcinoma. The tumor cells were positive for CDX-2 and cytokeratin 20 and negative for cytokeratin 7 and thyroid transcription factor-1, consistent with an enteric/colonic-type adenocarcinoma, demonstrating progressive atypia and malignancy. CONCLUSIONS: Malignant transformation of a mature intracranial teratoma portends a poor prognosis. The exact histopathological diagnosis can facilitate treatment of these patients. CDX-2 is a specific robust marker for identifying differentiation of a mature intracranial teratoma into a colonic adenocarcinoma. This positive staining can also be observed in primary colonic and other adenocarcinomas. To the best of our knowledge, this is the first report of the use of CDX-2 in the diagnosis of an intracranial malignancy. The triangulation of clinical progression, radiographic findings, and histopathological and immunohistochemistry findings provided clues regarding this unique transformation.

Validation of an effective implantable pump-infusion system for chronic convection-enhanced delivery of intracerebral topotecan in a large animal model.

OBJECTIVE: Intracerebral convection-enhanced delivery (CED) has been limited to short durations due to a reliance on externalized catheters. Preclinical studies investigating topotecan (TPT) CED for glioma have suggested that prolonged infusion improves survival. Internalized pump-catheter systems may facilitate chronic infusion. The authors describe the safety and utility of long-term TPT CED in a porcine model and correlation of drug distribution through coinfusion of gadolinium. METHODS: Fully internalized CED pump-catheter systems were implanted in 12 pigs. Infusion algorithms featuring variable infusion schedules, flow rates, and concentrations of a mixture of TPT and gadolinium were characterized over increasing intervals from 4 to 32 days. Therapy distribution was measured using gadolinium signal on MRI as a surrogate. A 9-point neurobehavioral scale (NBS) was used to identify side effects. RESULTS: All animals tolerated infusion without serious adverse events. The average NBS score was 8.99. The average maximum volume of distribution (Vdmax) in chronically infused animals was 11.30 mL and represented 32.73% of the ipsilateral cerebral hemispheric volume. Vdmax was achieved early during infusions and remained relatively stable despite a slight decline as the infusion reached steady state. Novel tissue TPT concentrations measured by liquid chromatography mass spectroscopy correlated with gadolinium signal intensity on MRI (p = 0.0078). CONCLUSIONS: Prolonged TPT-gadolinium CED via an internalized system is safe and well tolerated and can achieve a large Vdmax, as well as maintain a stable Vd for up to 32 days. Gadolinium provides an identifiable surrogate for measuring drug distribution. Extended CED is potentially a broadly applicable and safe therapeutic option in select patients.

Per Visit Emergency Department Expenditures By Insurance Type, 1996-2015.

Between 1996 and 2015, mean annual increases in per visit emergency department (ED) expenditures were significantly greater for private insurance than Medicare, Medicaid, and no insurance, with no corresponding difference in ED charges. Expenditures as a proportion of charges decreased for all insurers over time. Private insurance had the highest expenditure-to-charge ratio in each year.