Citations

OBJECTIVE Artificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks. RESEARCH DESIGN AND METHODS Thirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported adhering to consensus recommendations on reporting of AP trials. RESULTS Twenty-nine patients completed the trial. HbA1c, 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (−0.3, 95% CI −0.5 to −0.2, P < 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9% (−3.1, 95% CI −4.1 to −2.1, P < 0.001) and overnight from 4.1 to 1.1% (−3.1, 95% CI −4.2 to −1.9, P < 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes thereafter, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events. CONCLUSIONS Use of our novel adaptive AP yielded significant reductions in HbA1c and hypoglycemia.

Summary Objective A prospective multicenter phase III trial was undertaken to evaluate the performance and tolerability in the epilepsy monitoring unit ( EMU ) of an investigational wearable surface electromyographic ( sEMG ) monitoring system for the detection of generalized tonic–clonic seizures ( GTCSs ). Methods One hundred ninety‐nine patients with a history of GTCSs who were admitted to the EMU in 11 level IV epilepsy centers for clinically indicated video‐electroencephalographic monitoring also received sEMG monitoring with a wearable device that was worn on the arm over the biceps muscle. All recorded sEMG data were processed at a central site using a previously developed detection algorithm. Detected GTCSs were compared to events verified by a majority of three expert reviewers. Results For all subjects, the detection algorithm detected 35 of 46 (76%, 95% confidence interval [CI] = 0.61–0.87) of the GTCSs, with a positive predictive value ( PPV ) of 0.03 and a mean false alarm rate ( FAR ) of 2.52 per 24 h. For data recorded while the device was placed over the midline of the biceps muscle, the system detected 29 of 29 GTCSs (100%, 95% CI = 0.88–1.00), with a detection delay averaging 7.70 s, a PPV of 6.2%, and a mean FAR of 1.44 per 24 h. Mild to moderate adverse events were reported in 28% (55 of 199) of subjects and led to study withdrawal in 9% (17 of 199). These adverse events consisted mostly of skin irritation caused by the electrode patch that resolved without treatment. No serious adverse events were reported. Significance Detection of GTCSs using an sEMG monitoring device on the biceps is feasible. Proper positioning of this device is important for accuracy, and for some patients, minimizing the number of false positives may be challenging.

Background Emergency 9‐1‐1 callers use a wide range of terms to describe abnormal breathing in persons with out‐of‐hospital cardiac arrest ( OHCA ). These breathing descriptors can obstruct the telephone cardiopulmonary resuscitation ( CPR ) process. Methods and Results We conducted an observational study of emergency call audio recordings linked to confirmed OHCA s in a statewide Utstein‐style database. Breathing descriptors fell into 1 of 8 groups (eg, gasping, snoring). We divided the study population into groups with and without descriptors for abnormal breathing to investigate the impact of these descriptors on patient outcomes and telephone CPR process. Callers used descriptors in 459 of 2411 cases (19.0%) between October 1, 2010, and December 31, 2014. Survival outcome was better when the caller used a breathing descriptor (19.6% versus 8.8%, P <0.0001), with an odds ratio of 1.63 (95% confidence interval, 1.17–2.25). After exclusions, 379 of 459 cases were eligible for process analysis. When callers described abnormal breathing, the rates of telecommunicator OHCA recognition, CPR instruction, and telephone CPR were lower than when callers did not use a breathing descriptor (79.7% versus 93.0%, P <0.0001; 65.4% versus 72.5%, P =0.0078; and 60.2% versus 66.9%, P =0.0123, respectively). The time interval between call receipt and OHCA recognition was longer when the caller used a breathing descriptor (118.5 versus 73.5 seconds, P <0.0001). Conclusions Descriptors of abnormal breathing are associated with improved outcomes but also with delays in the identification of OHCA . Familiarizing telecommunicators with these descriptors may improve the telephone CPR process including OHCA recognition for patients with increased probability of survival.

OBJECTIVEThe subspecialization of neurosurgical practice is an ongoing trend in modern neurosurgery. However, it remains unclear whether the degree of surgeon specialization is associated with improved patient outcomes. The authors hypothesized that a trend toward increased neurosurgeon specialization was associated with improved patient morbidity and mortality rates.METHODSThe Nationwide Inpatient Sample (NIS) was used (1998–2009). Patients were included in a spinal analysis cohort for instrumented spine surgery involving the cervical spine (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 81.31–81.33, 81.01–81.03, 84.61–84.62, and 84.66) or lumbar spine (codes 81.04–81.08, 81.34–81.38, 84.64–84.65, and 84.68). A cranial analysis cohort consisted of patients receiving a parenchymal excision or lobectomy operation (codes 01.53 and 01.59). Surgeon specialization was measured using unique surgeon identifiers in the NIS and defined as the proportion of a surgeon’s total practice dedicated to cranial or spinal cases.RESULTSA total of 46,029 and 231,875 patients were identified in the cranial and spinal analysis cohorts, respectively. On multivariate analysis in the cranial analysis cohort (after controlling for overall surgeon volume, patient demographic data/comorbidities, hospital characteristics, and admitting source), each percentage-point increase in a surgeon’s cranial specialization (that is, the proportion of cranial cases) was associated with a 0.0060 reduction in the log odds of patient mortality (95% CI 0.0034–0.0086) and a 0.0042 reduction in the log odds of morbidity (95% CI 0.0032–0.0052). This resulted in a 15% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of cranial specialization. In the spinal analysis cohort, each percentage-point increase in a surgeon’s spinal specialization was associated with a 0.0122 reduction in the log odds of mortality (95% CI 0.0074–0.0170) and a 0.0058 reduction in the log odds of morbidity (95% CI 0.0049–0.0067). This resulted in a 26.8% difference in the predicted probability of mortality for neurosurgeons at the 75th versus the 25th percentile of spinal specialization.CONCLUSIONSFor both spinal and cranial surgery patient cohorts derived from the NIS database, increased surgeon specialization was significantly and independently associated with improved mortality and morbidity rates, even after controlling for overall case volume.

OBJECTIVEChordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat.METHODSThirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor–engrafted (n = 11), JHC7 tumor–engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E–based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin.RESULTSThe spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma–engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma–engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor–engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats.CONCLUSIONSThe authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors’ knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.