Dynamic Opportunities for Medical Students to Assume the Roles of "Medical Teacher".

The traditional undergraduate medical education curriculum focuses on bolstering knowledge for practice and building clinical skills. However, as future clinicians, medical students will be tasked with teaching throughout their careers, first as residents and then as attendings. Here, we describe teaching opportunities for students that foster their development as future teachers and potential clinician educators. These offerings are diverse in their focus and duration and are offered across various levels of the curriculum - including course-based learning, longitudinal electives, and extra-curricular opportunities for medical students who have a passion for teaching.

Household livelihood resilience of pastoralists and smallholders to climate change in Western Himalaya, India.

Smallholders and pastoralists are particularly vulnerable to the impacts of climate change due to their high reliance on socio-ecological systems for their livelihood. Building their resilience to these adverse effects of climate change is crucial for mitigating their vulnerabilities, especially in remote and fragile ecosystems. This study aims to assess the climate change livelihood resilience of smallholders and pastoralists in the Indian Himalayas. We build a livelihood resilience index, using the three dimensions of resilience, namely assimilative capacity, autopoiesis and cognitive ability, and weighed using entropy-TOPSIS approach The dimensions of resilience was estimated through indicators by a household survey of 289 randomly selected respondents across the three districts of Garhwal Himalayas. The results showed that the livelihood resilience of smallholders was greater than pastoralists. Among pastoralists, settlement brought positive changes to their livelihood, opening the gateway to access basic facilities. Key findings of the study indicate that public policy should focus towards information accessibility, encouraging environmental awareness and conservation, promoting social inclusion and cooperatives, and fostering grass root organization structures like forest-level organisation through informality to strengthen the resilience of communities to climate change.

Case report of bilateral middle ear effusion requiring myringotomy and tube placement following inferior U-shaped nasopharyngeal flap elevation for endonasal odontoidectomy: investigation of causality.

We describe a patient with symptomatic os odontoideum and a previous history of C1-2 wiring who underwent successful treatment with a staged endonasal odontoidectomy and C1-2 revision of instrumentation. Access to the odontoid process was gained through the endonasal corridor using an inverted U-shaped nasopharyngeal flap (IUNF). Post-operatively, the patient experienced resolution of her presenting neurologic symptoms but developed conductive hearing loss secondary to bilateral middle ear effusion, requiring bilateral myringotomy and tube placement 3 months post-operatively. We hypothesize this dysfunction may have resulted from surgical edema, packing buttressing the IUNF, or some combination thereof. In this manuscript, we review the evolution of the nasopharyngeal exposure for odontoidectomy and whether an IUNF may predispose to this complication.

Anterior occipital condyle screw placement through the endonasal corridor: proof of concept study with cadaveric analysis.

PURPOSE: Odontoidectomy for ventral compressive pathology may result in O-C1 and/or C1-2 instability. Same-stage endonasal C1-2 spinal fusion has been advocated to eliminate risks associated with separate-stage posterior approaches. While endonasal methods for C1 instrumentation and C1-2 trans-articular stabilization exist, no hypothetical construct for endonasal occipital instrumentation has been validated. We provide an anatomic description of anterior occipital condyle (AOC) screw endonasal placement as proof-of-concept for endonasal craniocervical stabilization. METHODS: Eight adult, injected cadaveric heads were studied for placing 16 AOC screws endonasally. Thin-cut CT was used for registration. After turning a standard inferior U-shaped nasopharyngeal flap endonasally, 4 mm × 22 mm AOC screws were placed with a 0° driver using neuronavigation. Post-placement CT scans were obtained to determine: site-of-entry, measured from the endonasal projection of the medial O-C1 joint; screw angulation in sagittal and axial planes, proximity to critical structures. RESULTS: Average site-of-entry was 6.88 mm lateral and 9.74 mm rostral to the medial O-C1 joint. Average angulation in the sagittal plane was 0.16° inferior to the palatal line. Average angulation in the axial plane was 23.97° lateral to midline. Average minimum screw distances from the jugular bulb and hypoglossal canal were 4.80 mm and 1.55 mm. CONCLUSION: Endonasal placement of AOC screws is feasible using a 0° driver. Our measurements provide useful parameters to guide optimal placement. Given proximity of hypoglossal canal and jugular bulb, neuronavigation is recommended. Biomechanical studies will ultimately be necessary to evaluate the strength of AOC screws with plate-screw constructs utilizing endonasal C1 lateral mass or C1-2 trans-articular screws as inferior fixation points.

C1 Lateral Mass Screw Placement Through Endonasal Corridor for Purpose of O-C1 Fusion: Morphometric Analysis in Cadaveric Specimens.

BACKGROUND: Odontoidectomy may pose some risks for O-C1 and/or C1-C2 instability, with previous authors reporting techniques for endonasal C1-C2 fusion. However, no technique for endonasal O-C1 fusion currently exists. We sought to describe the feasibility of endonasal anterior C1 (AC1) screw placement for endonasal O-C1 fusion. METHODS: Seven adult cadaveric heads were studied for endonasal placement of 14 C1 screws. Using thin-cut computed tomography (CT)-based "snapshot" neuronavigation assistance, 4 mm x 22 mm screws were placed in the C1 lateral mass using a 0° driver. Post-placement CT scans were obtained to determine site-of-entry measured from C1 anterior tubercle, screw angulation in axial and sagittal planes, and screw proximity to the central canal and foramen transversarium. RESULTS: Average site-of-entry was 16.57 mm lateral, 2.23 mm rostral, and 5.53 mm deep to the anterior-most portion of the C1 ring. Average axial angulation was 19.49° lateral to midline, measured at the C1 level. Average sagittal angulation was 13.22° inferior to the palatal line, measured from the hard palate to the opisthion. Bicortical purchase was achieved in 11 screws (78.6%). Partial breach of the foramen transversarium was observed in 2 screws (14.3%), violation of the O-C1 joint space in 1 (7.1%), and violation of the central canal in 0 (0%). Average minimum screw distances from the unviolated foramen transversaria and central canal were 1.97 mm and 4.04 mm. CONCLUSIONS: Navigation-assisted endonasal placement of AC1 screws is feasible. Additional studies should investigate the biomechanical stability of anterior C1 screw-plating systems, with anterior condylar screws as superior fixation point, compared to traditional posterior O-C1 fusion.

Machine Learning in Neuro-Oncology, Epilepsy, Alzheimer's Disease, and Schizophrenia.

Applications of machine learning (ML) in translational medicine include therapeutic drug creation, diagnostic development, surgical planning, outcome prediction, and intraoperative assistance. Opportunities in the neurosciences are rich given advancement in our understanding of the brain, expanding indications for intervention, and diagnostic challenges often characterized by multiple clinical and environmental factors. We present a review of ML in neuro-oncology, epilepsy, Alzheimer's disease, and schizophrenia to highlight recent progression in these field, optimizing machine learning capabilities in their current forms. Supervised learning models appear to be the most commonly incorporated algorithm models for machine learning across the reviewed neuroscience disciplines with primary aim of diagnosis. Accuracy ranges are high from 63% to 99% across all algorithms investigated. Machine learning contributions to neurosurgery, neurology, psychiatry, and the clinical and basic science neurosciences may enhance current medical best practices while also broadening our understanding of dynamic neural networks and the brain.

Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT.

TRIAL DESIGN: A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne®, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. METHODS: Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 µg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. RESULTS: A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. LIMITATIONS: The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. FUTURE WORK: Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. CONCLUSIONS: Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17405024. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 68. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy, affecting approximately one in four women. Sometimes, medical treatment (i.e. tablets) may be offered to start or speed up the miscarriage process in order for the womb to empty itself. A drug called misoprostol (a tablet that makes the womb contract) is currently recommended for this treatment. However, the addition of another drug called mifepristone [a tablet that reduces pregnancy hormones (Mifegyne^®, Exelgyn, Paris, France)] might help the miscarriage to resolve more quickly. Therefore, we carried out the MifeMiso trial to test if mifepristone plus misoprostol is more effective than misoprostol alone in resolving miscarriage within 7 days. Women were randomly allocated by a computer to receive either mifepristone or placebo, followed by misoprostol 2 days later. Neither the women nor their health-care professionals knew which treatment they received. Some women also talked to the researchers about their experiences of taking part in the study. In total, 711 women were randomised to receive either mifepristone plus misoprostol or placebo plus misoprostol. Overall, 83% of women who received mifepristone plus misoprostol had miscarriage resolution within 7 days, compared with 76% of the women who received a placebo plus misoprostol. Surgery was required less often in women who received mifepristone plus misoprostol: 17% of women who received it required surgery, compared with 25% of women who received the placebo. Treatment with mifepristone did not appear to have any negative effects. Treatment with mifepristone plus misoprostol was more cost-effective than misoprostol alone, with an average saving of £182 per woman. Having taken part in the study, most women would choose medical management again and would recommend it to someone they knew who was experiencing a miscarriage.

Spine Surgery in the Octogenarian Population: A Comparison of Demographics, Surgical Approach, and Healthcare Utilization With the PearlDiver Database.

Background With the recent advances in technology and healthcare, increasing numbers of individuals over the age of 80 will require surgical intervention for spinal pathology. Given the risk of increased complications in the elderly, a limited number of spinal surgeries are performed on octogenarians every year. This makes it difficult to generalize the trends and outcomes of these surgeries to a greater population. This study attempts to understand the trends in the safety profile and healthcare utilization across the United States for octogenarians undergoing spinal fusion and/or decompression surgery for spinal stenosis and/or degenerative disease using the PearlDiver database. Methodology Patients who underwent fusion and/or decompression for stenosis and/or degenerative diseases were extracted using International Classification of Disease ninth and tenth revisions (ICD-9 prior to October 2015, ICD-10 after) from 2007 to 2016 in the PearlDiver database. Three comparative groups were considered: (1) primary fusion without concurrent decompression, (2) primary decompression with concurrent fusion, and (3) fusion with concurrent decompression. Outcomes of interest were patient characteristics, demographics, length of stay, surgery hospitalization payments, and discharge disposition. These outcomes were compared to patients over the age of 20 who also underwent spinal surgery. Results A total of 9,715 patients who underwent spinal surgery were identified in the search. Of the 9,139 patients, 503 were octogenarians and 73 were nonagenarians. Octogenarians and nonagenarians diagnosed with spinal stenosis were more likely to undergo decompression alone rather than fusion or both fusion and decompression (21 for both fusion and decompression; p < 0.0001). Patients diagnosed with both spinal stenosis and degeneration were more likely to undergo both fusion and decompression than fusion or decompression alone (239 for both, 208 for decompression alone, and 23 for fusion alone; p < 0.0001). No statistically significant difference was found in the percentage of patients discharged home following either fusion or decompression or both surgeries (p = 0.0737). The mean length of stay for patients in the 20-79-year age group was 2.79 days, whereas for the octogenarian and nonagenarian cohort it was 3.85 days. The index hospitalization pay for patients in the 20-79-year age group was $19,220, whereas for the octogenarians and nonagenarians cohort it was $15,091. Conclusions Patients over the age of 80 were more likely to undergo either a fusion procedure or a decompression procedure alone rather than both unless they were diagnosed with spinal degeneration. The PearlDiver database analysis indicates that the length of stay for octogenarians and nonagenarians is longer than that for patients in the 20-79-year age group, and that younger patients are more likely to be discharged earlier than patients over the age of 80. Moreover, we observed that the index hospitalization pay was higher for patients over the age of 20 than for octogenarians and nonagenarians in all cases except for a fusion procedure.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. METHODS: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 µg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Treadmill-Based Gait Kinematics in the Yucatan Mini Pig.

Yucatan miniature pigs (YMPs) are similar to humans in spinal cord size as well as physiological and neuroanatomical features, making them a useful model for human spinal cord injury. However, little is known regarding pig gait kinematics, especially on a treadmill. In this study, 12 healthy YMPs were assessed during bipedal and/or quadrupedal stepping on a treadmill at six speeds (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 km/h). Kinematic parameters, including limb coordination and proximal and distal limb angles, were measured. Findings indicate that YMPs use a lateral sequence footfall pattern across all speeds. Stride and stance durations decreased with increasing speed whereas swing duration showed no significant change. Across all speeds assessed, no significant differences were noted between hindlimb stepping parameters for bipedal or quadrupedal gait with the exception of distal limb angular kinematics. Specifically, significant differences were observed between locomotor tasks during maximum flexion (quadrupedal > bipedal), total excursion (bipedal > quadrupedal), and the phase relationship between the timing of maximum extension between the right and left hindlimbs (bipedal > quadrupedal). Speed also impacted maximum flexion and right-left phase relationships given that significant differences were found between the fastest speed (3.5 km/h) relative to each of the other speeds. This study establishes a methodology for bipedal and quadrupedal treadmill-based kinematic testing in healthy YMPs. The treadmill approach used was effective in recruiting primarily the spinal circuitry responsible for the basic stepping patterns as has been shown in cats. We recommend 2.5 km/h (0.7 m/sec) as a target walking gait for pre-clinical studies using YMPs, which is similar to that used in cats.

Long-Term Comparison of Health Care Utilization and Reoperation Rates in Patients Undergoing Cervical Disc Arthroplasty and Anterior Cervical Discectomy and Fusion for Cervical Degenerative Disc Disease.

BACKGROUND: Thus study was a retrospective cohort analysis. Anterior cervical discectomy and fusion (ACDF) has been the gold-standard procedure for single-level degenerative disc disease (DDD). Recently, cervical disc arthroplasty (CDA) has become increasingly prevalent as an alternative intervention. OBJECTIVE: To examine the long-term costs and reoperation rates associated with CDA and ACDF for the treatment of single-level DDD. METHODS: In the present study, we performed a retrospective cohort analysis using the MarketScan database of patients who underwent either ACDF or CDA between 2007 and 2011 and had 5 years postsurgery follow-up. Outcomes related to the health care utilization, cost, and reoperation were analyzed after propensity score matching (PSM). RESULTS: Of 12,434 patients, 12,099 underwent ACDF and 335 CDA. Length of hospital stay and initial hospitalization cost was higher after ACDF compared with CDA. More patients undergoing CDA had early physical therapy compared with patients undergoing ACDF (CDA 30.15% vs. ACDF 22.39%; P = 0.0176). Five years after surgery, there was no significant difference in overall payments between patients undergoing ACDF and patients undergoing CDA. Reoperation rates were comparable at 5 years after the index procedure (CDA 8.06% vs. ACDF 9.25%; P = 0.5862). Patients who underwent ACDF showed decreased use of tramadol after surgery (15.09% before surgery vs. 9.55% after surgery; P < 0.0001). CONCLUSIONS: We found no difference in health care utilization between ACDF and CDA procedures for DDD 5 years after surgery. Also, there was no difference in reoperation rates during the study period. ACDF resulted in significant reduction in overall opioid use after versus before procedure.

Practical Bioinformatic DNA-Sequencing Pipeline for Detecting Oncogene Amplification and EGFRvIII Mutational Status in Clinical Glioblastoma Samples.

Glioblastoma is a malignant brain tumor with dismal prognosis. Oncogenic mutations in glioblastoma frequently affect receptor tyrosine kinase pathway components that are challenging to quantify because of heterogeneous expression. EGFRvIII, a common oncogenic receptor tyrosine kinase mutant protein in glioblastoma, potentiates tumor malignancy and is an emerging tumor-specific immunotarget, underlining the need for its more accessible and quantitative detection. We used normalized next-generation sequencing data from 117 brain and 371 reference clinical tumor samples to detect focal gene amplifications across the commercial Ion AmpliSeq Cancer Hotspot Panel version 2 and infer EGFRvIII status based on relative coverage dropout of the gene's truncated region within EGFR. In glioblastomas (n = 45), amplification of EGFR [18 (40%)], PDGFRA [3 (7%)], KIT [2 (4%)], MET [1 (2%)], and AKT1 [1 (2%)] was detected. With respect to EGFR and PDGFRA amplification, there was near-complete agreement between next-generation sequencing and in situ hybridization. Consistent with previous reports, this method detected EGFRvIII exclusively in EGFR-amplified glioblastomas [8 (44%)], which was confirmed using long-range PCR. Our study offers a practical method for detecting oncogene amplifications and large intragenic mutations in a clinically implemented hotspot panel that can be quantified using z scores. The validated detection of EGFRvIII using DNA sequencing eliminates problems with transcript degradation, and the provided script facilitates efficient incorporation into a laboratory's bioinformatic pipeline.

Squamous cell carcinoma in situ arising in mature cystic teratoma.

Mature cystic teratomas of ovary are common tumors. A few may exhibit malignant degeneration, most of these being invasive squamous cell carcinoma. We report a rare case of pure squamous cell carcinoma in situ in benign cystic teratoma.